RESUMO
OBJECTIVES: Few studies have evaluated racial and ethnic differences in several immune-mediated inflammatory diseases (IMIDs) or overlap syndrome (the co-occurrence of ≥ 2 IMIDs). We assessed associations between race and ethnicity and prevalence of IMIDs and overlap syndrome using US claims and electronic health records from 2021. STUDY DESIGN: Retrospective cohort study of 10.8 million adults. METHODS: We identified the 10 most prevalent IMIDs among frequently discussed IMIDs. We estimated associations between the 5 most prevalent IMIDs and overlap syndrome in Hispanic and non-Hispanic Asian and Black adults using non-Hispanic White adults as the referent and stratifying by sex and age (20-39, 40-59, and ≥ 60 years). RESULTS: Inflammatory bowel disease (IBD), systemic lupus erythematosus (SLE), multiple sclerosis (MS), and rheumatoid arthritis (RA) were the most prevalent IMIDs in all races and ethnicities. We observed positive associations (P < .0001) between Hispanic and non-Hispanic Black adults and SLE, Asian women of all ages and Asian men younger than 60 years and SLE, Black women younger than 60 years and MS, and Hispanic and non-White women 60 years or older and RA. Hispanic and non-White adults of all age groups had inverse associations (P < .0001) with IBD. Non-Hispanic Black adults of all ages and Hispanic and non-Hispanic Asian women 40 years or older had inverse associations (P < .0001) with psoriasis/psoriatic arthritis. Overlap syndrome was rare among all groups, with some variation in which IMIDs co-occurred. CONCLUSIONS: We found racial and ethnic differences in the prevalence and co-occurrence of IMIDs in this sample of US adults. Because misdiagnoses are relatively frequent for patients with IMIDs, awareness of racial and ethnic variations in IMIDs could aid early diagnosis and improve disease management.
Assuntos
Artrite Reumatoide , Doenças Autoimunes , Doenças Inflamatórias Intestinais , Lúpus Eritematoso Sistêmico , Adulto , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Grupos Raciais , Estudos Retrospectivos , Prevalência , Doenças Autoimunes/epidemiologia , Lúpus Eritematoso Sistêmico/epidemiologia , Artrite Reumatoide/epidemiologia , Doenças Inflamatórias Intestinais/epidemiologia , Agentes de ImunomodulaçãoRESUMO
BACKGROUND: We studied the association between iron intake and polymorphisms in the iron transporter gene SLC40A1 and the risk of tuberculosis. METHODS: We compared iron intake, the frequency of SLC40A1 mutations, and interactions among these variables among 98 tuberculosis patients and 125 controls in Kwazulu-Natal, South Africa. RESULTS: Four SLC40A1 single-nucleotide polymorphisms (SNPs) were associated with an increased risk of tuberculosis and 1 SNP with reduced risk. We also found a gene-environment interaction for 4 nonexonic SNPs and iron intake. CONCLUSIONS: This pilot study demonstrated an association between polymorphisms in SLC40A1 and tuberculosis and provided evidence of an interaction between dietary iron and SLC40A1.
Assuntos
Proteínas de Transporte de Cátions/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Tuberculose/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Estudos de Associação Genética , Humanos , Masculino , Pessoa de Meia-Idade , África do SulRESUMO
BACKGROUND: Multiple studies of tuberculosis treatment have indicated that patients with diabetes mellitus may experience poor outcomes.We performed a systematic review and meta-analysis to quantitatively summarize evidence for the impact of diabetes on tuberculosis outcomes. METHODS: We searched PubMed, EMBASE and the World Health Organization Regional Indexes from 1 January 1980 to 31 December 2010 and references of relevant articles for reports of observational studies that included people with diabetes treated for tuberculosis. We reviewed the full text of 742 papers and included 33 studies of which 9 reported culture conversion at two to three months, 12 reported the combined outcome of failure and death, 23 reported death, 4 reported death adjusted for age and other potential confounding factors, 5 reported relapse, and 4 reported drug resistant recurrent tuberculosis. RESULTS: Diabetes is associated with an increased risk of failure and death during tuberculosis treatment. Patients with diabetes have a risk ratio (RR) for the combined outcome of failure and death of 1.69 (95% CI, 1.36 to 2.12). The RR of death during tuberculosis treatment among the 23 unadjusted studies is 1.89 (95% CI, 1.52 to 2.36), and this increased to an effect estimate of 4.95 (95% CI, 2.69 to 9.10) among the 4 studies that adjusted for age and other potential confounding factors. Diabetes is also associated with an increased risk of relapse (RR, 3.89; 95% CI, 2.43 to 6.23). We did not find evidence for an increased risk of tuberculosis recurrence with drug resistant strains among people with diabetes. The studies assessing sputum culture conversion after two to three months of tuberculosis therapy were heterogeneous with relative risks that ranged from 0.79 to 3.25. CONCLUSIONS: Diabetes increases the risk of failure and death combined, death, and relapse among patients with tuberculosis. This study highlights a need for increased attention to treatment of tuberculosis in people with diabetes, which may include testing for suspected diabetes, improved glucose control, and increased clinical and therapeutic monitoring.
Assuntos
Antituberculosos/administração & dosagem , Complicações do Diabetes , Tuberculose/complicações , Tuberculose/tratamento farmacológico , Humanos , Análise de Sobrevida , Falha de Tratamento , Resultado do Tratamento , Tuberculose/mortalidadeRESUMO
The pe and ppe genes are unique to mycobacteria and are widely speculated to play a role in tuberculosis pathogenesis. However, little is known about how expression of these genes is controlled. Elucidating the regulatory control of genes found exclusively in mycobacteria, such as the pe and ppe gene families, may be key to understanding the success of this pathogen. In this study, we used a transposon mutagenesis approach to elucidate pe and ppe regulation. This resulted in the identification of Rv0485, a previously uncharacterized transcriptional regulator. Microarray and quantitative real-time PCR analysis confirmed that disruption of Rv0485 reduced the expression of the pe13 and ppe18 gene pair (Rv1195 and Rv1196), defined the Rv0485 regulon, and emphasized the lack of global regulation of pe and ppe genes. The in vivo phenotype of the Rv0485 transposon mutant strain (Rv0485::Tn) was investigated in the mouse model, where it was demonstrated that the mutation has minimal effect on bacterial organ burden. Despite this, disruption of Rv0485 allowed mice to survive for significantly longer, with substantially reduced lung pathology in comparison with mice infected with wild-type Mycobacterium tuberculosis. Infection of immune-deficient SCID mice with the Rv0485::Tn strain also resulted in extended survival times, suggesting that Rv0485 plays a role in modulation of innate immune responses. This is further supported by the finding that disruption of Rv0485 resulted in reduced secretion of proinflammatory cytokines by infected murine macrophages. In summary, we have demonstrated that disruption of a previously uncharacterized transcriptional regulator, Rv0485, results in reduced expression of pe13 and ppe18 and attenuation of M. tuberculosis virulence.
Assuntos
Antígenos de Bactérias/biossíntese , Proteínas de Bactérias/fisiologia , Regulação Bacteriana da Expressão Gênica , Mycobacterium tuberculosis/fisiologia , Mycobacterium tuberculosis/patogenicidade , Transativadores/fisiologia , Fatores de Transcrição/fisiologia , Fatores de Virulência/fisiologia , Sequência de Aminoácidos , Estruturas Animais/microbiologia , Animais , Proteínas de Bactérias/biossíntese , Proteínas de Bactérias/genética , Contagem de Colônia Microbiana , Elementos de DNA Transponíveis , Feminino , Perfilação da Expressão Gênica , Técnicas de Inativação de Genes , Pulmão/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos SCID , Dados de Sequência Molecular , Mutagênese Insercional , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Alinhamento de Sequência , Análise de Sobrevida , Transativadores/genética , Fatores de Transcrição/genética , Tuberculose/microbiologia , Tuberculose/patologia , Fatores de Virulência/genéticaRESUMO
OBJECTIVES: The prevalence of obesity is disproportionately higher among African-Americans and Hispanics as compared to whites. We investigated the role of biogeographic ancestry (BGA) on adiposity and changes in adiposity in the Boston Area Community Health Survey. METHODS: We evaluated associations between BGA, assessed via Ancestry Informative Markers, and adiposity (body mass index (BMI), percent body fat (PBF), and waist-to-hip ratio (WHR)) and changes in adiposity over 7 years for BMI and WHR and 2.5 years for PBF, per 10% greater proportion of BGA using multivariable linear regression. We also examined effect-modification by demographic and socio-behavioral variables. RESULTS: We observed positive associations between West-African ancestry and cross-sectional BMI (percent difference=0.62%; 95% CI: 0.04%, 1.20%), and PBF (ß=0.35; 95% CI: 0.11, 0.58). We also observed significant effect-modification of the association between West-African ancestry and BMI by gender (p-interaction: <0.002) with a substantially greater association in women. We observed no main associations between Native-American ancestry and adiposity but observed significant effect-modification of the association with BMI by diet (p-interaction: <0.003) with inverse associations among participants with higher Healthy Eating Scores. No associations were observed between BGA and changes in adiposity over time. CONCLUSION: Findings support that West-African ancestry may contribute to high prevalence of total body adiposity among African-Americans, particularly African-American women.
Assuntos
Adiposidade/etnologia , Adiposidade/genética , Negro ou Afro-Americano , Adulto , Idoso , Alelos , Índice de Massa Corporal , Boston , Estudos Transversais , Feminino , Marcadores Genéticos/genética , Geografia , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/etnologia , Obesidade/genética , Fatores Sexuais , Relação Cintura-QuadrilRESUMO
OBJECTIVES: Numerous studies continue to report poorer glycaemic control, and a higher incidence of diabetes-related complications among African-Americans and Hispanic-Americans as compared with non-Hispanic Caucasians with type 2 diabetes. We examined racial/ethnic differences in receipt of hypoglycaemic medications and glycaemic control in a highly insured Massachusetts community sample of individuals with type 2 diabetes. SETTING: Community-based sample from Boston, Massachusetts, USA. PARTICIPANTS: 682 patients with physician-diagnosed diabetes from the third wave of the Boston Area Community Health Survey (2010-2012). The study included approximately equal proportions of African-Americans, Hispanics and Caucasians. METHODS: We examined racial/ethnic disparities in diabetes treatment by comparing proportions of individuals on mutually exclusive diabetes treatment regimens across racial/ethnic subgroups. Using multivariable linear and logistic regression, we also examined associations between race/ethnicity and glycaemic control in the overall population, and within treatment regimens, adjusting for age, gender, income, education, health insurance, health literacy, disease duration, diet and physical activity. RESULTS: Among those treated (82%), the most commonly prescribed antidiabetic regimens were biguanides only (31%), insulin only (23%), and biguanides and insulin (16%). No overall racial/ethnic differences in treatment or glycaemic control (per cent difference for African-Americans: 6.18, 95% CI -1.00 to 13.88; for Hispanic-Americans: 1.01, 95% CI -10.42 to 12.75) were observed. Within regimens, we did not observe poorer glycaemic control for African-Americans prescribed biguanides only, insulin only or biguanides combined with insulin/sulfonylureas. However, African-Americans prescribed miscellaneous regimens had higher risk of poorer glycaemic control (per cent difference=23.37, 95% CI 7.25 to 43.33). There were no associations between glycaemic levels and Hispanic ethnicity overall, or within treatment regimens. CONCLUSIONS: Findings suggest a lack of racial/ethnic disparities in diabetes treatment patterns and glycaemic control in this highly insured Massachusetts study population. Future studies are needed to understand impacts of increasing insurance coverage on racial/ethnic disparities in treatment patterns and related outcomes.