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1.
Nat Commun ; 12(1): 772, 2021 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-33536424

RESUMO

Systemic lupus erythematosus (SLE), a worldwide autoimmune disease with high heritability, shows differences in prevalence, severity and age of onset among different ancestral groups. Previous genetic studies have focused more on European populations, which appear to be the least affected. Consequently, the genetic variations that underlie the commonalities, differences and treatment options in SLE among ancestral groups have not been well elucidated. To address this, we undertake a genome-wide association study, increasing the sample size of Chinese populations to the level of existing European studies. Thirty-eight novel SLE-associated loci and incomplete sharing of genetic architecture are identified. In addition to the human leukocyte antigen (HLA) region, nine disease loci show clear ancestral differences and implicate antibody production as a potential mechanism for differences in disease manifestation. Polygenic risk scores perform significantly better when trained on ancestry-matched data sets. These analyses help to reveal the genetic basis for disparities in SLE among ancestral groups.


Assuntos
Heterogeneidade Genética , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla/métodos , Lúpus Eritematoso Sistêmico/genética , Polimorfismo de Nucleotídeo Único , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , Grupo com Ancestrais do Continente Europeu/genética , Predisposição Genética para Doença/etnologia , Genótipo , Humanos , Desequilíbrio de Ligação , Lúpus Eritematoso Sistêmico/etnologia
2.
MMWR Morb Mortal Wkly Rep ; 70(7): 236-239, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33600382

RESUMO

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with manifestations that vary widely in severity. Although minority populations are at higher risk for SLE and have more severe outcomes (1), population-based estimates of mortality by race and ethnicity are often lacking, particularly for Asian and Hispanic/Latino persons. Among 812 patients in the California Lupus Surveillance Project (CLSP) during 2007-2009 (2,3), who were matched to the 2007-2017 National Death Index (NDI), 16.6% had died by 2017. This proportion included persons of White (14.4%), Black (25%), Asian (15.3%), and Hispanic/Latino (15.5%) race/ethnicity. Standardized mortality ratios (SMRs) of observed-to-expected deaths among persons with SLE within each racial/ethnic group were 2.3, 2.0, 3.8, and 3.9, respectively. These findings provide the first population-based estimates of mortality among Asian and Hispanic/Latino persons with SLE. Coordination of robust care models between primary care providers and rheumatologists could ensure that persons with SLE receive a timely diagnosis and appropriate treatments that might help address SLE-associated mortality.


Assuntos
Americanos Asiáticos/estatística & dados numéricos , Hispano-Americanos/estatística & dados numéricos , Lúpus Eritematoso Sistêmico/etnologia , Lúpus Eritematoso Sistêmico/mortalidade , Grupos Minoritários/estatística & dados numéricos , Adolescente , Adulto , Idoso , California/epidemiologia , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade/etnologia , Adulto Jovem
3.
Medicine (Baltimore) ; 99(40): e22614, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019481

RESUMO

BACKGROUND: The relationship between MTHFR (5, 10-methylene tetrahydrofolate reductase) gene polymorphisms and Systemic Lupus Erythematosus (SLE) has been wildly studied, but the results are still conflicting. Therefore, the purpose of this meta and pooled analysis was to identify the role of the MTHFR SNP (single nucleotide polymorphism, rs1801133) in SLE in a large sample of subjects and to assess the risk of SLE. METHODS: Data were collected from EMBASE, PubMed and China National Knowledge Infrastructure from inception to August, 2019. Summary odds ratio (OR) with 95% confidence interval (CI) was applied to assess the association. Subgroup and sensitivity analysis were performed to assess the potential sources of heterogeneity of the pooled estimation. RESULTS: We identified seven eligible studies involving 882 cases and 991 controls. MTHFR rs1801133 T carrier was significantly associated with increased risk of SLE when comparing to C allele [ORs were 1.766 (1.014-3.075) for T carrier vs CC, P = .04]. Furthermore, the results of the subgroup analysis by genotyping methods suggested that T allele significantly contributed to the risk of SLE for both by polymerase chain reaction-TaqMan (PCR-TaqMan) [10.111 (2.634-38.813) for TT vs CC, 3.467 (1.324-9.078) for CT vs CC and 3.744 (1.143-12.264) for TT vs C carrier]. Also the results of the subgroup analysis by ethnicity suggested that T allele significantly contributed to the risk of SLE for Asians [9.679 (4.444-21.082) for TT vs CC, 5.866 (3.021-11.389) for T carrier vs CC and 8.052 (3.861-16.795) for TT vs C carrier]. CONCLUSION: This cumulative meta-analysis showed that the MTHFR SNP (rs1801133) contributed to susceptibility of SLE. However, more multicentre well-designed case-control studies and larger sample sizes are exceedingly required to validate our findings in the future.


Assuntos
Lúpus Eritematoso Sistêmico/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo de Nucleotídeo Único/genética , Alelos , Grupo com Ancestrais do Continente Asiático/genética , Portador Sadio , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Lúpus Eritematoso Sistêmico/etnologia , Masculino , Medição de Risco , Sensibilidade e Especificidade
4.
Clin Appl Thromb Hemost ; 26: 1076029620943671, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32702995

RESUMO

Severe acute respiratory syndrome coronavirus 2 infection (COVID-19) is known to induce severe inflammation and activation of the coagulation system, resulting in a prothrombotic state. Although inflammatory conditions and organ-specific diseases have been shown to be strong determinants of morbidity and mortality in patients with COVID-19, it is unclear whether preexisting differences in coagulation impact the severity of COVID-19. African Americans have higher rates of COVID-19 infection and disease-related morbidity and mortality. Moreover, African Americans are known to be at a higher risk for thrombotic events due to both biological and socioeconomic factors. In this review, we explore whether differences in baseline coagulation status and medical management of coagulation play an important role in COVID-19 disease severity and contribute to racial disparity trends within COVID-19.


Assuntos
Afro-Americanos , Betacoronavirus , Infecções por Coronavirus/etnologia , Pandemias , Pneumonia Viral/etnologia , Trombofilia/etnologia , Tromboembolia Venosa/etnologia , Afro-Americanos/genética , Anemia Falciforme/sangue , Anemia Falciforme/etnologia , Anticoagulantes/uso terapêutico , Proteínas Sanguíneas/análise , Proteínas Sanguíneas/genética , Ensaios Clínicos como Assunto , Comorbidade , Infecções por Coronavirus/sangue , Infecções por Coronavirus/complicações , Fator VIII/análise , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Estudos de Associação Genética , Predisposição Genética para Doença , Disparidades em Assistência à Saúde , Humanos , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/etnologia , Masculino , Seleção de Pacientes , Pneumonia Viral/sangue , Pneumonia Viral/complicações , Polimorfismo de Nucleotídeo Único , Prevalência , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/etnologia , Fatores de Risco , Determinantes Sociais da Saúde , Fatores Socioeconômicos , Trombofilia/sangue , Trombofilia/tratamento farmacológico , Trombofilia/etiologia , Tromboembolia Venosa/sangue , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle
5.
Artigo em Inglês | MEDLINE | ID: mdl-32231129

RESUMO

INTRODUCTION: Over 400,000 slaves were taken from Africa and brought to Charleston, South Carolina, as part of the transatlantic slave trade during the 18th and 19th centuries. Due to these negative historical events, the healthcare of African Americans in Charleston may be compromised in regard to chronic illnesses and other conditions affecting minorities, such as lupus. MATERIALS AND METHODS: The current study used an ethnographic approach to obtain the perspectives of lupus patients with the goal of identifying gaps within current research. In addition to patient perspectives, the geographical location of Charleston, South Carolina was considered through inquiries around culture, community, advocacy, and client/patient interaction to establish a narrative for the themes that emerged. RESULTS: The eleven major themes identified were connectedness, knowledge, experience with lupus, compliance, clinical trial participation, career and planning for the future, visits, access to resources, lifestyle, transition from child to adult care, and an overarching theme of self-management. CONCLUSION: Understanding healthcare perceptions and decision-making among culturally diverse populations, particularly those who have been defined by centuries of substandard care, marginalization, exploitation, and distrust, is critical to the development of culturally tailored interventions designed to improve patient outcomes and reduce health disparities.


Assuntos
Tomada de Decisões , Assistência à Saúde/história , Disparidades em Assistência à Saúde/história , Lúpus Eritematoso Sistêmico/terapia , Adulto , Afro-Americanos , Criança , Feminino , Pesquisa sobre Serviços de Saúde , História do Século XXI , Humanos , Lúpus Eritematoso Sistêmico/etnologia , Participação do Paciente , South Carolina , Transição para Assistência do Adulto
6.
Clin Rheumatol ; 39(2): 413-418, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31897958

RESUMO

Patients with concomitant HIV-1 infection and systemic lupus erythematosus (SLE) followed longitudinally at an HIV outpatient clinic from 1994 to 2019 were examined. Patients met 1982 and 1997 ACR classification criteria for SLE at the Thomas Street clinic from 1994 to 2019. Clinical and demographic comparisons were made with a non HIV-SLE patient cohort, the Lupus in Minorities Studies, Nature versus Nurture (LUMINA) study. Twenty-two patients with concomitant HIV-1 infection and SLE were identified, including 18 females, 3 males, and 1 male to female transgender. Overall, 81.8% of SLE-HIV patients were African-American compared to 55.3% of the 5856 patients seen at the HIV clinic from 2016 to 2017 (p = 0.02, OR = 3.6). There were 12 patients that developed HIV-1 in the setting of SLE and 10 patients that developed SLE in the setting HIV-1. This demographic distribution was significant when compared with the 1604 unique patients in the HIV rheumatology clinic from 1994 to 2019 (p = 0.03, OR = 5.9) and also significant when compared with the 5856 patients attending the county HIV clinic overall in 2016-2017 (p = 0.008, OR = 7.2). When comparing with the non-HIV SLE cohort, anti-dsDNA antibodies were noted less frequently in all HIV-SLE patients (p = 0.0002) including all sub-cohorts of our patients. Skin/mucosal involvement (p = 0.0003) and cytopenias (p = 0.0001) occurred less frequently in the patients that were diagnosed with HIV after their SLE diagnosis compared to non-HIV SLE patients. In a large county HIV clinic setting, the prevalence of SLE was significantly higher in African American women. Anti-dsDNA antibodies were less frequent in HIV-1 positive SLE patients.Key Points• This paper presents clinical and laboratory data on the largest cohort of SLE patients with HIV-1 infection reported to date.• The prevalence of SLE in a large outpatient HIV-1 clinic was larger than reported in HIV negative population studies.• The prevalence of SLE was particularly high in black HIV-1 infected women.• Skin/mucosal involvement and anti-ds DNA antibodies were less common in patients with HIV-1 and SLE compared to patients with SLE without SLE>.


Assuntos
Infecções por HIV/epidemiologia , Lúpus Eritematoso Sistêmico/epidemiologia , Adulto , Afro-Americanos/estatística & dados numéricos , Assistência Ambulatorial , Anticorpos Antinucleares/imunologia , DNA/imunologia , Grupo com Ancestrais do Continente Europeu , Feminino , HIV-1 , Humanos , Estudos Longitudinais , Lúpus Eritematoso Sistêmico/etnologia , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prevalência
7.
Arthritis Care Res (Hoboken) ; 72(5): 622-629, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31115180

RESUMO

OBJECTIVE: The California Lupus Surveillance Project (CLSP) is a population-based registry of individuals with systemic lupus erythematosus (SLE) residing in San Francisco County, California from 2007 to 2009, with a special focus on Asian/Pacific Islander and Hispanic patients. We used retrospective CLSP data to analyze racial and ethnic differences in lupus manifestations and in the timing and risk of developing severe manifestations. METHODS: A total of 724 patients with SLE were retrospectively identified. Prevalence ratios (PRs) of SLE manifestations were calculated using Poisson regression models stratified by race/ethnicity and adjusted for sex, age at SLE diagnosis, and disease duration. We studied onset of severe SLE manifestations after SLE diagnosis using Kaplan-Meier methods to examine time-to-event and Cox proportional hazards regression models to estimate hazard ratios (HRs). White patients were the referent group in all analyses. RESULTS: African Americans, Asian/Pacific Islanders, and Hispanic patients had increased prevalence of renal manifestations (PR 1.74 [95% confidence interval (95% CI) 1.40-2.16], PR 1.68 [95% CI 1.38-2.05], and PR 1.35 [95% CI 1.05-1.74], respectively). Furthermore, African Americans had increased prevalence of neurologic manifestations (PR 1.49 [95% CI 1.12-1.98]), and both African Americans (PR 1.09 [95% CI 1.04-1.15]) and Asian/Pacific Islanders (PR 1.07 [95% CI 1.01-1.13]) had increased prevalence of hematologic manifestations. African Americans, Asian/Pacific Islanders, and Hispanic patients, respectively, had higher risk of developing lupus nephritis (HR 2.4 [95% CI 1.6-3.8], HR 4.3 [95% CI 2.9-6.4], and HR 2.3 [95% CI 1.4-3.8]) and thrombocytopenia (HR 2.3 [95% CI 1.1-4.4], HR 2.3 [95% CI 1.3-4.2], and HR 2.2 [95% CI 1.1-4.7]). Asian/Pacific Islander and Hispanic patients had higher risk of developing antiphospholipid syndrome (HR 2.5 [95% CI 1.4-4.4] and HR 2.6 [95% CI 1.3-5.1], respectively). CONCLUSION: This is the first epidemiologic study comparing lupus manifestations among 4 major racial and ethnic groups. We found substantial differences in the prevalence of several clinical SLE manifestations among racial/ethnic groups and discovered that African Americans, Asian/Pacific Islanders, and Hispanic patients are at increased risk of developing several severe manifestations following a diagnosis of SLE.


Assuntos
Grupos de Populações Continentais , Grupos Étnicos , Disparidades nos Níveis de Saúde , Lúpus Eritematoso Sistêmico/etnologia , Adolescente , Adulto , California/epidemiologia , Progressão da Doença , Feminino , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/etnologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/diagnóstico , Vasculite Associada ao Lúpus do Sistema Nervoso Central/etnologia , Masculino , Pessoa de Meia-Idade , Vigilância da População , Prevalência , Prognóstico , Fatores Raciais , Sistema de Registros , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Adulto Jovem
8.
Arthritis Care Res (Hoboken) ; 72(2): 225-232, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31507071

RESUMO

OBJECTIVE: Lupus low disease activity state (LLDAS) is a potential treat-to-target goal in systemic lupus erythematosus (SLE). This study determined predictors of time to reach LLDAS in a longitudinal cohort. METHODS: Patients were grouped according to LLDAS status at cohort entry. Those who did not satisfy LLDAS at cohort entry were analyzed prospectively. The Kaplan-Meier approach was used to estimate the time to LLDAS. Cox regression was used to identify patient characteristics that were associated with time to LLDAS. RESULTS: The probability of LLDAS attainment within 1 year was 52% for Caucasians, 36% for African Americans, and 33% for SLE patients with renal involvement. The median time to LLDAS was 1.1 years. In multivariable models, African American ethnicity, baseline prednisone >10 mg daily, hypocomplementemia, baseline damage, and baseline renal activity remained significant predictors of longer time to attain LLDAS, while disease duration <1 year and cutaneous activity were associated with earlier attainment. CONCLUSION: LLDAS is potentially attainable in the majority of SLE patients. The time to LLDAS was found to be longer in African American patients with SLE. Characteristics of African American patients with SLE, such as renal activity and hypocomplementemia, were also independent predictors of slower attainment of LLDAS. These findings point to the need to include African American patients with SLE in both clinical and pharmaceutical research.


Assuntos
Afro-Americanos/etnologia , Progressão da Doença , Grupo com Ancestrais do Continente Europeu/etnologia , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/etnologia , Índice de Gravidade de Doença , Adulto , Estudos de Coortes , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Tempo
9.
Arthritis Care Res (Hoboken) ; 72(8): 1159-1162, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-31199590

RESUMO

OBJECTIVE: To determine if low disease activity state (LDAS)/remission predicts a better health-related quality of life (HRQoL). METHODS: Patients with systemic lupus erythematosus from a single center and having completed at least 2 visits were included. Visits were performed every 6 months. HRQoL was measured with the LupusQoL questionnaire. The definition of remission included a Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score of 0, prednisone daily dosage of ≤5 mg/day, and immunosuppressive drugs on maintenance dose. LDAS was defined as a SLEDAI-2K score of ≤4, prednisone daily dosage of ≤7.5 mg/day, and immunosuppressive drugs as maintenance therapy. For these analyses, remission and LDAS were combined as one variable. Generalized estimating equations were calculated, using as the outcome 1 of each of the 8 components of the LupusQoL questionnaire in the subsequent visit and the activity state in the previous visit. Multivariable models were adjusted for possible confounders. RESULTS: A total of 243 patients were included. During the follow-up, 590 visits (61.6%) were categorized as LDAS/remission. LDAS/remission predicted a better HRQoL in the components of physical health (B = 4.17 [95% confidence interval (95% CI) 1.20, 7.14]; P = 0.006), pain (B = 6.47 [95% CI 3.18, 9.76]; P < 0.001), planning (B = 4.97 [95% CI 1.43, 8.52]; P = 0.006), burden to others (B = 4.12 [95% CI 0.24, 8.01]; P = 0.037], emotional health (B = 4.50 [95% CI 1.56, 7.44]; P = 0.003), and fatigue (B = 3.25 [95% CI 0.04, 6.47]; P = 0.048). CONCLUSION: Being in LDAS/remission predicts a better HRQoL, especially in the components of physical health, pain, planning, burden to others, emotional health, and fatigue.


Assuntos
Grupos Étnicos/psicologia , Lúpus Eritematoso Sistêmico/psicologia , Qualidade de Vida , Índice de Gravidade de Doença , Adolescente , Adulto , Estudos de Coortes , Feminino , Humanos , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/etnologia , Masculino , Pessoa de Meia-Idade , Peru/etnologia , Prednisona/uso terapêutico , Indução de Remissão , Inquéritos e Questionários , Resultado do Tratamento , Adulto Jovem
10.
Rheumatology (Oxford) ; 59(1): 90-98, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31236574

RESUMO

OBJECTIVE: LN is one of the most common and severe manifestations of SLE. Our aim was to test the association of SLE risk loci with LN risk in childhood-onset SLE (cSLE) and adult-onset SLE (aSLE). METHODS: Two Toronto-based tertiary care SLE cohorts included cSLE (diagnosed <18 years) and aSLE patients (diagnosed ⩾18 years). Patients met ACR and/or SLICC SLE criteria and were genotyped on the Illumina Multi-Ethnic Global Array or Omni1-Quad arrays. We identified those with and without biopsy-confirmed LN. HLA and non-HLA additive SLE risk-weighted genetic risk scores (GRSs) were tested for association with LN risk in logistic models, stratified by cSLE/aSLE and ancestry. Stratified effect estimates were meta-analysed. RESULTS: Of 1237 participants, 572 had cSLE (41% with LN) and 665 had aSLE (30% with LN). Increasing non-HLA GRS was significantly associated with increased LN risk [odds ratio (OR) = 1.26; 95% CI 1.09, 1.46; P = 0.0006], as was increasing HLA GRS in Europeans (OR = 1.55; 95% CI 1.07, 2.25; P = 0.03). There was a trend for stronger associations between both GRSs and LN risk in Europeans with cSLE compared with aSLE. When restricting cases to proliferative LN, the magnitude of these associations increased for both the non-HLA (OR = 1.30; 95% CI 1.10, 1.52; P = 0.002) and HLA GRS (OR = 1.99; 95% CI 1.29, 3.08; P = 0.002). CONCLUSION: We observed an association between known SLE risk loci and LN risk in children and adults with SLE, with the strongest effect observed among Europeans with cSLE. Future studies will include SLE-risk single nucleotide polymorphisms specific to non-European ancestral groups and validate findings in an independent cohort.


Assuntos
Idade de Início , Loci Gênicos/genética , Predisposição Genética para Doença/genética , Lúpus Eritematoso Sistêmico/genética , Nefrite Lúpica/genética , Adolescente , Adulto , Criança , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Predisposição Genética para Doença/etnologia , Genótipo , Humanos , Modelos Logísticos , Lúpus Eritematoso Sistêmico/etnologia , Nefrite Lúpica/etnologia , Masculino , Razão de Chances , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco , Adulto Jovem
11.
Clin Rheumatol ; 39(2): 365-373, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31705325

RESUMO

INTRODUCTION: Smoking has been associated with increased incidence, severity of cutaneous lupus, and lupus activity. We looked at the association of both smoking and ethnicity with the individual damage items from the SLICC/ACR Damage Index. METHODS: Poisson regression was used to model the total SLICC/ACR Damage Index score against ever smoking. Cox regression was used to assess the relationship between time to individual damage items and ever smoking. Furthermore, we compared SLICC/ACR Damage Index items among African-American and Caucasian ever smokers. RESULTS: The study included 2629 patients, 52.6% Caucasian and 39.3% African-American. The prevalence of ever smokers was 35.8%. There was no significant difference in total SLICC/ACR Damage Index score between ever smokers and never smokers after adjustment for ethnicity, gender, age at diagnosis, and years of education. Ever smokers had more atherosclerotic cardiovascular damage and skin damage compared to non-smokers. Caucasian SLE patients who ever smoked were more likely to have muscle atrophy and atherosclerosis compared to Caucasian non-smokers. African-American patients who ever smoked were more likely to have skin damage compared to African-American non-smokers. African-Americans who smoked were more likely to have many more damage items (cataract, renal damage, pulmonary hypertension, cardiomyopathy, deforming or erosive arthritis, avascular necrosis, skin damage, and diabetes) compared to Caucasians who smoked. CONCLUSION: Our analysis proved the major effect of smoking on cardiovascular and cutaneous damage. Surprisingly, cardiovascular damage items had higher hazard ratios in Caucasian smokers than non-smokers while skin damage items hazard ratios were higher in African-American smokers compared to non-smokers.Key Points• This study is the largest cohort study to date evaluating the effect of smoking on the cumulative SLICC/ACR Damage Index and its individual damage items.• It is the only study that examined the effect of smoking on individual items of the SLICC/ACR Damage Index in terms of Caucasians vs. African-American ethnicity.• Our analysis proved the major effect of smoking on cardiovascular and cutaneous damage. Compared to non-smokers, Caucasian smokers had higher risk of cardiovascular damage while African-American smokers had more skin damage.• African-Americans who smoked were more likely to have many more damage items (cataract, renal damage, pulmonary hypertension, cardiomyopathy, deforming or erosive arthritis, avascular necrosis, skin damage, and diabetes) compared to Caucasians who smoked.


Assuntos
Afro-Americanos/estatística & dados numéricos , Artrite/etnologia , Doenças Cardiovasculares/etnologia , Fumar Cigarros/epidemiologia , Diabetes Mellitus/etnologia , Grupo com Ancestrais do Continente Europeu/estatística & dados numéricos , Falência Renal Crônica/etnologia , Lúpus Eritematoso Sistêmico/etnologia , Adulto , Alopecia/epidemiologia , Alopecia/etnologia , Artrite/epidemiologia , Aterosclerose/epidemiologia , Aterosclerose/etnologia , Cardiomiopatias/epidemiologia , Cardiomiopatias/etnologia , Doenças Cardiovasculares/epidemiologia , Catarata/epidemiologia , Catarata/etnologia , Cicatriz/epidemiologia , Cicatriz/etnologia , Estudos de Coortes , Diabetes Mellitus/epidemiologia , Ex-Fumantes , Feminino , Humanos , Hipertensão Pulmonar/epidemiologia , Hipertensão Pulmonar/etnologia , Falência Renal Crônica/epidemiologia , Estudos Longitudinais , Lúpus Eritematoso Cutâneo/epidemiologia , Lúpus Eritematoso Cutâneo/etnologia , Lúpus Eritematoso Sistêmico/epidemiologia , Nefrite Lúpica/epidemiologia , Nefrite Lúpica/etnologia , Masculino , Pessoa de Meia-Idade , Atrofia Muscular/epidemiologia , Atrofia Muscular/etnologia , não Fumantes , Osteonecrose/epidemiologia , Osteonecrose/etnologia , Modelos de Riscos Proporcionais , Fumantes , Tempo , Estados Unidos/epidemiologia
12.
Autoimmun Rev ; 19(1): 102423, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31733367

RESUMO

PURPOSE: AIDs may disproportionately impact specific racial groups, but autoimmune (AID) prevalence information by minority racial group is sparse for many AIDs. The objective of this analysis was to supplement previously published AID prevalence rates by providing information on race rate ratios (minority race populations compared to Caucasian populations) in the United States. Preliminary to estimating race rate ratios, contemporary US-specific, health care utilization-based AID prevalence rates and female-to-male ratios were estimated and compared to previously published AID prevalence rates. METHODS: We used a large national electronic medical record database of 52 million individuals to estimate age-adjusted direct standardized rates for 22 AIDs for 2010 through 2016 by gender, race, and US census division. These were compared to previously published estimates. RESULTS: Female-to-male ratios were comparable with published studies. Almost all observed Multiracial AID rates were significantly higher than Caucasian rates, as well as 9 of 22 AID rates observed among Native Americans and 8 of 22 AID rates estimated among African-American patients. Regional variation was noted: highest African-American systemic lupus erythematosus rates were observed in the West North Central and South Atlantic divisions, highest African-American multiple sclerosis rates in the South Atlantic and Pacific divisions, and highest Native American rheumatoid arthritis rates in the West North Central, Mountain, and Pacific divisions. CONCLUSIONS: Substantial AID heterogeneity exists by race and by geographic area. An important research area is further exploring factors related to heterogeneity such as potential interactions between genetic susceptibility and environmental factors.


Assuntos
Doenças Autoimunes/etnologia , Doenças Autoimunes/epidemiologia , Lúpus Eritematoso Sistêmico/etnologia , Lúpus Eritematoso Sistêmico/epidemiologia , Afro-Americanos , Feminino , Geografia Médica , Humanos , Masculino , Prevalência , Razão de Masculinidade , Estados Unidos/epidemiologia , Estados Unidos/etnologia
13.
Lupus ; 29(1): 27-36, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31801040

RESUMO

BACKGROUND: Systemic lupus erythematosus (SLE) is regarded as a prototype autoimmune disease because it can serve as a means for studying differences between ethnic minorities and sex. Traditionally, all Hispanics have been bracketed within the same ethnic group, but there are differences between Hispanics from Spain and those from Latin America, not to mention other Spanish-speaking populations. OBJECTIVES: This study aimed to determine the demographic and clinical characteristics, severity, activity, damage, mortality and co-morbidity of SLE in Hispanics belonging to the two ethnic groups resident in Spain, and to identify any differences. METHODS: This was an observational, multi-centre, retrospective study. The demographic and clinical variables of patients with SLE from 45 rheumatology units were collected. The study was conducted in accordance with Good Clinical Practice guidelines. Hispanic patients from the registry were divided into two groups: Spaniards or European Caucasians (EC) and Latin American mestizos (LAM). Comparative univariate and multivariate statistical analyses were carried out. RESULTS: A total of 3490 SLE patients were included, 90% of whom were female; 3305 (92%) EC and 185 (5%) LAM. LAM patients experienced their first lupus symptoms four years earlier than EC patients and were diagnosed and included in the registry younger, and their SLE was of a shorter duration. The time in months from the first SLE symptoms to diagnosis was longer in EC patients, as were the follow-up periods. LAM patients exhibited higher prevalence rates of myositis, haemolytic anaemia and nephritis, but there were no differences in histological type or serositis. Anti-Sm, anti-Ro and anti-RNP antibodies were more frequently found in LAM patients. LAM patients also had higher levels of disease activity, severity and hospital admissions. However, there were no differences in damage index, mortality or co-morbidity index. In the multivariate analysis, after adjusting for confounders, in several models the odds ratio (95% confidence interval) for a Katz severity index >3 in LAM patients was 1.45 (1.038-2.026; p = 0.02). This difference did not extend to activity levels (i.e. SLEDAI >3; 0.98 (0.30-1.66)). CONCLUSION: SLE in Hispanic EC patients showed clinical differences compared to Hispanic LAM patients. The latter more frequently suffered nephritis and higher severity indices. This study shows that where lupus is concerned, not all Hispanics are equal.


Assuntos
Progressão da Doença , Lúpus Eritematoso Sistêmico/etnologia , Grupo com Ancestrais do Continente Europeu/estatística & dados numéricos , Feminino , Humanos , América Latina/etnologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Masculino , Sistema de Registros , Estudos Retrospectivos , Índice de Gravidade de Doença , Espanha/epidemiologia
14.
J Immunol Res ; 2019: 2397698, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31815152

RESUMO

Objectives: This study was to investigate the association of melatonin (MTN) pathway gene's single-nucleotide polymorphisms (SNPs) with susceptibility to systemic lupus erythematosus (SLE). Methods: We recruited 495 SLE patients and 493 healthy controls, 11 tag SNPs in MTN receptor 1a (MTNR1a), MTNR1b, and arylalkylamine N-acetyltransferase (AANAT) genes were genotyped and analyzed. Serum MTN concentration was determined by enzyme-linked immunosorbent assay (ELISA) kits. Results: Two SNPs of AANAT gene (rs8150 and rs3760138) associated with the risk of SLE; CC carriers of rs8150 had a lower risk as compared to GG (OR = 0.537, 95% CI: 0.361, 0.799), whereas GG carrier in rs3760138 had an increased risk (OR = 1.823, 95% CI: 1.154, 2.880) compared to TT. However, we did not find any genetic association between the other nine SNPs with SLE risk. Case-only analysis showed associations of rs2165667 and rs1562444 with arthritis, rs10830962 with malar rash, rs3760138 with immunological abnormality, and rs8150 with hematological abnormality. Furthermore, a significant difference between plasma MTN levels with different genotypes of rs1562444 was observed. Haplotype analyses revealed that haplotype of CCTAT, CTAGT, and GGG was significantly associated with the increased risk in SLE susceptibility, but TCTAT and CTG appeared to be a protective haplotype. Conclusions: The present study supported the genetic association of MTN pathway genes with SLE susceptibility and specific clinical manifestations, suggesting the potential role of MTN pathway genes in the pathogenesis and development of SLE.


Assuntos
Arilalquilamina N-Acetiltransferase/genética , Lúpus Eritematoso Sistêmico/genética , Melatonina/metabolismo , Polimorfismo de Nucleotídeo Único , Receptor MT1 de Melatonina/genética , Receptor MT2 de Melatonina/genética , Adulto , Arilalquilamina N-Acetiltransferase/metabolismo , Grupo com Ancestrais do Continente Asiático , Estudos de Casos e Controles , Feminino , Expressão Gênica , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Haplótipos , Humanos , Lúpus Eritematoso Sistêmico/etnologia , Lúpus Eritematoso Sistêmico/metabolismo , Lúpus Eritematoso Sistêmico/patologia , Masculino , Pessoa de Meia-Idade , Receptor MT1 de Melatonina/metabolismo , Receptor MT2 de Melatonina/metabolismo
15.
Autoimmunity ; 52(7-8): 289-293, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31707854

RESUMO

Recent large-scale genetic association studies have identified that several single nucleotide polymorphisms (SNPs) on X chromosome are correlated with risk of systemic lupus erythematosus (SLE) in Chinese population. The aim of this study was to estimate association between these loci and clinical features in female patients with SLE. Six SNPs identified in previous studies were genotyped. Odds ratio (OR) was calculated with adjusting for potential confounding factors. A total of 772 SLE patients were included in the final analysis. The data showed that 3 SNPs (rs5914778, rs3853839 and rs1059702) were marginally associated with several clinical subphenotypes. Furthermore, consistent associations were also found in two independent cohorts. However, the cumulative genetic risk score (GRS) was not associated with clinical manifestations as well as the disease activity index at disease diagnosis. In summary, genetic variants in X-linked genes may be potentially associated with presence of specific clinical feature. Further studies in distinct ethnical populations are required to clarify the association between these loci and presence of SLE clinical features.


Assuntos
Genes Ligados ao Cromossomo X , Predisposição Genética para Doença , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/genética , Adulto , Grupo com Ancestrais do Continente Asiático , Cromossomos Humanos X , Estudos de Coortes , Feminino , Estudo de Associação Genômica Ampla , Humanos , Lúpus Eritematoso Sistêmico/etnologia , Lúpus Eritematoso Sistêmico/patologia , Masculino , Razão de Chances , Polimorfismo de Nucleotídeo Único
17.
Lupus ; 28(13): 1571-1576, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31653192

RESUMO

OBJECTIVE: The objective of this analysis was to explore associations between paraoxonase-1 levels, gene polymorphisms and systemic lupus erythematosus. METHODS: Meta-analyses of paraoxonase-1 levels and Q192R and L55M and polymorphisms in systemic lupus erythematosus were conducted. RESULTS: Nine articles were incorporated in our meta-analysis, which uncovered that the paraoxonase-1 level was decreased in systemic lupus erythematosus compared to control (standard mean difference = -1.626, 95% confidence interval = -2.829--0.424, p = 0.008). Ethnicity-specific meta-analysis demonstrated a relation tendency between decreased paraoxonase-1 activity and lupus in Europeans (standard mean difference = -1.236, 95% confidence interval = -2.634-0.163, p = 0.083). Paraoxonase-1 activity was reduced in systemic lupus erythematosus in a single Arab and African population. Decreased paraoxonase-1 activity was found in a small sample of systemic lupus erythematosus patients (standard mean difference = -1.642, 95% confidence interval = -3.076--0.247, p = 0.021). Ethnicity-specific analysis indicated a relationship between the paraoxonase-1 55 M allele in the Arab systemic lupus erythematosus population. However, a lack of association with systemic lupus erythematosus and the paraoxonase-1 192 R allele was observed. CONCLUSIONS: Meta-analyses revealed reduced paraoxonase-1 activity in patients with systemic lupus erythematosus and found possible associations between systemic lupus erythematosus and paraoxonase-1 L55M polymorphism in a specific ethnic group.


Assuntos
Arildialquilfosfatase/metabolismo , Grupos Étnicos/genética , Lúpus Eritematoso Sistêmico/fisiopatologia , Alelos , Arildialquilfosfatase/genética , Humanos , Lúpus Eritematoso Sistêmico/enzimologia , Lúpus Eritematoso Sistêmico/etnologia , Polimorfismo Genético
18.
Lupus ; 28(14): 1619-1627, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31660790

RESUMO

OBJECTIVE: The heterogeneous spectrum of systemic lupus erythematosus (SLE) often presents with secondary complications such as cardiovascular disease (CVD), infections and neoplasms. Our study assessed whether the presence of SLE independently increases or reduces the disparities, accounting for the already higher risk of these outcomes among racial/ethnic minority groups without SLE. METHODS: We defined a cohort using electronic health records data (2005-2016) from a mixed-payer community-based outpatient setting in California serving patients of diverse racial/ethnic backgrounds. The eligible population included adult patients with SLE and matched non-SLE patients (≥18 years old). SLE was the primary exposure. The following outcomes were identified: pneumonia, other infections, CVD and neoplasms. For each racial/ethnic group, we calculated the proportion of incident co-morbidities by SLE exposure, followed by logistic regression for each outcome with SLE as the exposure. We evaluated interaction on the additive and multiplicative scales by calculating the relative excess risk due to interaction and estimating the cross-product term in each model. RESULTS: We identified 1036 SLE cases and 8875 controls. The incidence for all outcomes was higher among the SLE exposed. We found little difference in the odds of the outcomes associated with SLE across racial/ethnic groups, even after multivariable adjustment. This finding was consistent on the multiplicative and additive scales. CONCLUSION: We demonstrated that SLE status does not independently confer substantial interaction or heterogeneity by race/ethnicity toward the risk of pneumonia, other infections, CVD or neoplasms. Further studies in larger datasets are necessary to validate this novel finding.


Assuntos
Doenças Cardiovasculares/etnologia , Grupos de Populações Continentais/estatística & dados numéricos , Grupos Étnicos/estatística & dados numéricos , Lúpus Eritematoso Sistêmico/etnologia , Adolescente , Adulto , Idoso , Assistência Ambulatorial/estatística & dados numéricos , California/epidemiologia , Estudos de Coortes , Comorbidade/tendências , Feminino , Humanos , Incidência , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
19.
Lupus ; 28(12): 1452-1459, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570051

RESUMO

OBJECTIVE: The aim of this study was to systematically review evidence regarding the association between CD40 polymorphisms and systemic lupus erythematosus and between soluble CD40 (sCD40) and CD40 ligand (sCD40L) levels and systemic lupus erythematosus. METHODS: We performed a meta-analysis on the association between CD40 rs4810495, rs1883832, and rs376545 polymorphisms and systemic lupus erythematosus risk and sCD40/sCD40L levels in patients with systemic lupus erythematosus and controls. RESULTS: Fourteen studies were included. Ethnicity-specific meta-analysis indicated a significant association between the T allele of CD40 rs4810485 polymorphism and systemic lupus erythematosus in Europeans (odds ratio = 0.715, 95% confidence interval = 0.641-0.832, p < 0.001) and a trend toward an association between the T allele and systemic lupus erythematosus in Asians (odds ratio = 1.255, 95% confidence interval = 0.978-1.810, p = 0.074). Furthermore, a significant association was reported between systemic lupus erythematosus and the C allele of CD40 rs1883832 polymorphism (odds ratio = 1.235, 95% confidence interval = 1.087-1.405, p = 0.001) and A allele of CD40 rs3765456 polymorphism and systemic lupus erythematosus in Asians (odds ratio = 1.184, 95% confidence interval = 1.040-1.348, p = 0.011). sCD40 and sCD40L levels were significantly higher in SLE than in controls (standardized mean difference = 1.564, 95% confidence interval = 0.256-2.872, p = 0.019 and standardized mean difference = 1.499, 95% confidence interval = 1.031-1.967, p < 0.001, respectively). Stratification based on ethnicity revealed higher sCD40L levels in the systemic lupus erythematosus group among European, Asian, North American, and Arab populations. CONCLUSIONS: Our meta-analyses found associations between CD40 rs4810495, rs1883832, and rs376545 polymorphisms and systemic lupus erythematosus susceptibility and significantly higher sCD40 and sCD40L levels in patients with systemic lupus erythematosus than in controls.


Assuntos
Antígenos CD40/genética , Ligante de CD40/sangue , Grupos Étnicos/genética , Lúpus Eritematoso Sistêmico/genética , Alelos , Antígenos CD40/sangue , Estudos de Casos e Controles , Grupos Étnicos/estatística & dados numéricos , Genótipo , Humanos , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/etnologia , Polimorfismo de Nucleotídeo Único/genética , Medição de Risco
20.
PLoS One ; 14(9): e0222343, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31539383

RESUMO

Flare of Systemic Lupus Erythematosus (SLE) may occur during pregnancy and puerperium. We studied the prevalence and factors associated with SLE relapse during pregnancy and post-partum period in a multi-ethnic SLE cohort. Consecutive SLE patients who attended the outpatient clinic were reviewed for previous history of pregnancies in our institution. Patients who had a complete antenatal, delivery, and post-partum follow up were included. Their medical records were retrospectively analysed to assess the disease activity at pre-pregnancy/conception, during antenatal, and post-partum period. Presence of flare episodes during pregnancy and puerperium were recorded. The pregnancy outcomes recorded include live birth, foetal loss, prematurity and intra-uterine growth restrictions (IUGR). Univariate and multivariable logistic regression with generalized estimating equations (GEE) analyses were performed to determine the factors associated with disease relapse and the pregnancy outcomes. A total of 120 patients with 196 pregnancies were included, with a live birth rate of 78.6%. Four (2.0%) were diagnosed to have SLE during pregnancy. The flare rate in pregnancy was 40.1% while post-partum 17.4%. Majority of the relapse in pregnancy occurred in haematological system (62.3%) followed by renal (53.2%), musculoskeletal (22.1%), and mucocutaneous (14.3%). In GEE analyses, active disease at conception was the independent predictor of SLE relapse during and after pregnancy, whereas older maternal age and Malay ethnicity were associated with higher flare during post-partum. HCQ use was significantly associated with reduced risk of flare in univariate analysis but it was no longer significant in the GEE analyses. Presence of disease flare in pregnancy was significantly associated with prematurity. In conclusion, pregnancy in SLE need to be planned during quiescent state as pre-pregnant active disease was associated with disease relapse in both during and after pregnancy. Malay patients had an increased risk of post-partum flare but further larger prospective studies are needed to confirm the association between pregnancies in the different ancestral background.


Assuntos
Lúpus Eritematoso Sistêmico/epidemiologia , Complicações na Gravidez/epidemiologia , Adulto , Grupos Étnicos/estatística & dados numéricos , Feminino , Humanos , Lúpus Eritematoso Sistêmico/etnologia , Lúpus Eritematoso Sistêmico/etiologia , Malásia/epidemiologia , Período Pós-Parto , Gravidez , Complicações na Gravidez/etnologia , Complicações na Gravidez/etiologia , Recidiva , Estudos Retrospectivos , Fatores de Risco
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