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1.
J Nepal Health Res Counc ; 21(3): 411-416, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38615211

RESUMO

BACKGROUND: Lip print patterns are unique in every individual. The uniqueness of lip print pattern assists in the personal identification. The objectives of the present study were to study the different lip print patterns among the children visiting Kanti Children's Hospital, and to compare the distribution of lip print patterns based on gender and race. METHODS: A cross-sectional study was conducted among 300 children visiting the Dental Outpatient Department of Kanti Children's Hospital, Kathmandu, Nepal. Convenience sampling method was used to choose the study subjects. Digital photography method was used to record the image of lips. RESULTS: The study showed 'Long vertical' (Type I) as the most frequent (41%) type of lip print pattern, whereas 'Unspecified' (Type V) was the least frequent (2.7%) type. Prevalence of 'Type I' pattern was significantly higher in males as compared to females (p=0.007) whereas prevalence of 'Type IV' pattern was significantly higher in females as compared to males (p=0.006). 'Type I' pattern was the commonest lip print pattern among both Caucasians and Mongolian, whereas 'Type V' (2%) and 'Type IV' (3.7%) were the least common lip print patterns in Caucasians and Mongolian children respectively. CONCLUSIONS: 'Long vertical' (Type I) was the most common lip print pattern among the children visiting the Dental Outpatient Department of Kanti Children's Hospital, Kathmandu, Nepal. Nevertheless, in higher or lesser numbers, all kinds of lip print patterns as described by Suzuki and Tsuchihashi were seen in the study population.


Assuntos
Lábio , Criança , Feminino , Humanos , Masculino , Povo Asiático , Estudos Transversais , Lábio/anatomia & histologia , Nepal , Pacientes Ambulatoriais , População Branca
2.
Glycobiology ; 34(6)2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38591797

RESUMO

AIM: Alpha-1-acid glycoprotein (AGP) is a highly glycosylated protein in human plasma and one of the most abundant acute phase proteins in humans. Glycosylation plays a crucial role in its biological functions, and alterations in AGP N-glycome have been associated with various diseases and inflammatory conditions. However, large-scale studies of AGP N-glycosylation in the general population are lacking. METHODS: Using recently developed high-throughput glycoproteomic workflow for site-specific AGP N-glycosylation analysis, 803 individuals from the Croatian island of Korcula were analyzed and their AGP N-glycome data associated with biochemical and physiological traits, as well as different environmental factors. RESULTS: After regression analysis, we found that AGP N-glycosylation is strongly associated with sex, somewhat less with age, along with multiple biochemical and physiological traits (e.g. BMI, triglycerides, uric acid, glucose, smoking status, fibrinogen). CONCLUSION: For the first time we have extensively explored the inter-individual variability of AGP N-glycome in a general human population, demonstrating its changes with sex, age, biochemical, and physiological status of individuals, providing the baseline for future population and clinical studies.


Assuntos
Orosomucoide , População Branca , Humanos , Orosomucoide/metabolismo , Masculino , Feminino , Glicosilação , Pessoa de Meia-Idade , Adulto , Idoso , Croácia
3.
South Med J ; 117(4): 199-205, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38569609

RESUMO

OBJECTIVES: Eradication of Helicobacter pylori reduces the risk of gastric cancer (GC). Individuals with type 2 diabetes mellitus (T2DM) are known to be at increased risk for GC. In a cohort of H. pylori-positive individuals, we assessed whether those with T2DM were at risk of persistent infection following H. pylori treatment compared with individuals without T2DM. METHODS: A random subset of all individuals diagnosed as having H. pylori without intestinal metaplasia at endoscopy from 2015 to 2019 were stratified evenly by race (Black and White). After excluding those with T1DM and those without eradication testing after H. pylori treatment, logistic regression analysis was used to determine the association of T2DM with the risk of persistent H. pylori infection following treatment. RESULTS: In 138 patients, H. pylori eradication rates did not differ between the 27% of individuals with T2DM compared to those without (81.1% vs 81.2%). After adjusting for age, race, and insurance status, we found no significant increased risk of persistent H. pylori infection for individuals with T2DM (odds ratio 1.40; 95% confidence interval 0.49-3.99). CONCLUSIONS: H. pylori eradication rates do not differ by T2DM status, providing support for clinical trials of H. pylori eradication to reduce GC incidence among high-risk populations in the United States, such as individuals with T2DM.


Assuntos
Diabetes Mellitus Tipo 2 , Infecções por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Humanos , Antibacterianos/uso terapêutico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Infecções por Helicobacter/complicações , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/epidemiologia , Fatores de Risco , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/prevenção & controle , Neoplasias Gástricas/diagnóstico , População Negra , População Branca
4.
Br Dent J ; 236(7): 556-561, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38609624

RESUMO

Bernard Smith was one of the most significant specialists in restorative dentistry of his generation. He was an inspiring undergraduate and postgraduate teacher, a noted international lecturer and a house-builder. Bernard was president of the British Society for Restorative Dentistry and first chairman of the Association of Consultants and Specialists in Restorative Dentistry.


Assuntos
Consultores , Odontologia , Masculino , Humanos , Estudantes , População Branca
5.
Br Dent J ; 236(7): 552-555, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38609623

RESUMO

Royal patronage is not something new. Engraved images of British royalty were used by early toothpaste manufacturers, dentists and perfumiers to convey royal endorsement to boost their product sales in the nineteenth and early twentieth centuries. Packaged in high-quality ceramic pots, these toothpastes and powders promoted cleaning, beautifying and preserving the teeth and gums. These fascinating containers, sealed with a transfer-printed lid, feature inventive designs and typefaces and highlight sophisticated manufacturing and marketing skills to entice consumers. Many have been re-discovered from the excavation of former rubbish tips and are often the only tangible evidence of long defunct businesses that elected to use this latest form of packaging.


Assuntos
Publicidade , Cremes Dentais , Humanos , Cerâmica , Comércio , População Branca
7.
Clin Transl Sci ; 17(4): e13784, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38563414

RESUMO

The inhibition of coagulation factor XI (FXI) presents an attractive approach for anticoagulation as it is not expected to increase the risk of clinically relevant bleeding and is anticipated to be at least as effective as currently available anticoagulants. Fesomersen is a conjugated antisense oligonucleotide that selectively inhibits the expression of FXI. The article describes three clinical studies that investigated the safety, pharmacokinetic (PK), and pharmacodynamic (PD) profiles of fesomersen after subcutaneous (s.c.) injection to healthy participants. The studies included participants from diverse ethnic backgrounds (Caucasian, Japanese, and Chinese). Fesomersen demonstrated good safety and tolerability in all three studies. No major bleeding events were observed. After single-dose s.c. injection, fesomersen was rapidly absorbed into the systemic circulation, with maximum fesomersen-equivalent (fesomersen-eq) concentrations (Cmax) in plasma observed within a few hours. After reaching Cmax, plasma fesomersen-eq concentrations declined in a biphasic fashion. The PD analyses showed that the injection of fesomersen led to dose-dependent reductions in FXI activity and increases in activated partial thromboplastin time (aPTT). The maximum observed PD effects were reached between Day 15 and 30, and FXI activity and aPTT returned to near-baseline levels by Day 90 after a single dose. The PK/PD profiles after a single injection were similar among the various ethnic groups. Collectively, the study results suggest that fesomersen has a favorable safety profile and predictable and similar PK and PD profiles across Chinese, Japanese, and Caucasian participants.


Assuntos
Fator XI , Hemorragia , Humanos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Voluntários Saudáveis , Tempo de Tromboplastina Parcial , População do Leste Asiático , População Branca
8.
Nat Commun ; 15(1): 3441, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38658550

RESUMO

Hyperuricemia is an essential causal risk factor for gout and is associated with cardiometabolic diseases. Given the limited contribution of East Asian ancestry to genome-wide association studies of serum urate, the genetic architecture of serum urate requires exploration. A large-scale cross-ancestry genome-wide association meta-analysis of 1,029,323 individuals and ancestry-specific meta-analysis identifies a total of 351 loci, including 17 previously unreported loci. The genetic architecture of serum urate control is similar between European and East Asian populations. A transcriptome-wide association study, enrichment analysis, and colocalization analysis in relevant tissues identify candidate serum urate-associated genes, including CTBP1, SKIV2L, and WWP2. A phenome-wide association study using polygenic risk scores identifies serum urate-correlated diseases including heart failure and hypertension. Mendelian randomization and mediation analyses show that serum urate-associated genes might have a causal relationship with serum urate-correlated diseases via mediation effects. This study elucidates our understanding of the genetic architecture of serum urate control.


Assuntos
Estudo de Associação Genômica Ampla , Hiperuricemia , Ácido Úrico , Humanos , Ácido Úrico/sangue , Hiperuricemia/genética , Hiperuricemia/sangue , Polimorfismo de Nucleotídeo Único , Povo Asiático/genética , Gota/genética , Gota/sangue , Predisposição Genética para Doença , População Branca/genética , Análise da Randomização Mendeliana , Herança Multifatorial , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/sangue , Hipertensão/genética , Hipertensão/sangue , Transcriptoma , Masculino , Proteínas de Ligação a DNA/genética
9.
Clin Epigenetics ; 16(1): 58, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38658973

RESUMO

Alzheimer's disease (AD) prevalence is twice as high in non-Hispanic Blacks (NHBs) as in non-Hispanic Whites (NHWs). The objective of this study was to determine whether aberrant methylation at imprint control regions (ICRs) is associated with AD. Differentially methylated regions (DMRs) were bioinformatically identified from whole-genome bisulfite sequenced DNA derived from brain tissue of 9 AD (5 NHBs and 4 NHWs) and 8 controls (4 NHBs and 4 NHWs). We identified DMRs located within 120 regions defined as candidate ICRs in the human imprintome ( https://genome.ucsc.edu/s/imprintome/hg38.AD.Brain_track ). Eighty-one ICRs were differentially methylated in NHB-AD, and 27 ICRs were differentially methylated in NHW-AD, with two regions common to both populations that are proximal to the inflammasome gene, NLRP1, and a known imprinted gene, MEST/MESTIT1. These findings indicate that early developmental alterations in DNA methylation of regions regulating genomic imprinting may contribute to AD risk and that this epigenetic risk differs between NHBs and NHWs.


Assuntos
Doença de Alzheimer , Metilação de DNA , População Branca , Humanos , Doença de Alzheimer/genética , Doença de Alzheimer/etnologia , Metilação de DNA/genética , População Branca/genética , Feminino , Masculino , Idoso , Negro ou Afro-Americano/genética , Idoso de 80 Anos ou mais , Impressão Genômica/genética , Epigênese Genética/genética , Estudos de Casos e Controles , População Negra/genética , Proteínas NLR/genética
10.
Cancer Med ; 13(8): e7151, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38650521

RESUMO

BACKGROUND: Ewing sarcoma (ES) is a malignant bone tumor most commonly affecting non-Hispanic White (NHW) adolescent males, though recognition among Hispanic individuals is rising. Prior population-based studies in the United States (US), utilizing Surveillance, Epidemiology, and End Results (SEER) have shown higher all-cause mortality among White Hispanics, Blacks, and those of low socioeconomic status (SES). Florida is not part of SEER but is home to unique Hispanic populations including Cubans, Puerto Ricans, South Americans that contrasts with the Mexican Hispanic majority in other US states. This study aimed to assess racial/ethnic disparities on incidence and survival outcomes among this diverse Florida patient population. METHODOLOGY: Our study examined all patients diagnosed with osseous ES (2005-2018) in Florida (n = 411) based on the state's population-based cancer registry dataset. Florida Age-adjusted Incidence Rates (AAIRs) were computed by sex and race-ethnicity and compared to the equivalent populations in SEER. Cause-specific survival disparities among Florida patients were examined using Kaplan-Meier analysis. Univariable and multivariable analyses using Cox regression were performed for race/ethnicity, with adjustment for age, sex, year of diagnosis, site of disease, staging, SES, and insurance type. RESULTS: There was a significantly higher incidence of osseous ES in Florida Hispanic males (AAIR 2.6/1,000,000); (95% CI: 2.0-3.2 per 1,000,000; n = 84) compared to the SEER Hispanic males (AAIR 1.2/1,000,000;1.1-1.4 per 1,000,000; n = 382). Older age, distant metastasis, lack of chemotherapy or surgical resection were statistically significant determinants of poor survival while SES, insurance status and race-ethnicity were not. However, among nonmetastatic ES, Florida Hispanics had an increased risk of death compared to Florida NHW (adjusted Hazard Ratio 2.32; 95%CI: 1.20-4.46; p = 0.012). CONCLUSIONS: Florida Hispanic males have a higher-than-expected incidence of osseous ES compared to the US. Hispanics of both sexes show remarkably worse survival for nonmetastatic disease compared to NHW. This disparity is likely multifactorial and requires further in-depth studies.


Assuntos
Sarcoma de Ewing , Humanos , Florida/epidemiologia , Masculino , Sarcoma de Ewing/mortalidade , Sarcoma de Ewing/epidemiologia , Sarcoma de Ewing/terapia , Sarcoma de Ewing/etnologia , Feminino , Incidência , Adolescente , Adulto , Criança , Adulto Jovem , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/epidemiologia , Neoplasias Ósseas/etnologia , Programa de SEER , Hispânico ou Latino/estatística & dados numéricos , Pré-Escolar , Pessoa de Meia-Idade , Disparidades nos Níveis de Saúde , Lactente , População Branca/estatística & dados numéricos
11.
Asian Pac J Cancer Prev ; 25(3): 767-776, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38546059

RESUMO

Studies on the CXCL12 rs1801157 polymorphism show that this polymorphism is involved in development of breast cancer, but its specific relationships or effects are not consistent. The purpose of this meta-analysis was to investigate the association between CXCL12 rs1801157 polymorphism and susceptibility to breast cancer. PubMed, Scopus, Embase, the Cochrane Library, Web of Science, and CNKI were searched for eligible studies through February 01, 2023. A total of ten studies with 2093 cases and 2302 controls were included in this meta-analysis. Overall, there is a significant association between CXCL12 rs1801157 polymorphism and risk of breast cancer under the homozygote genetic model (AA vs. GG, OR= 1.350, 95% CI: 1.050-1.734, p= 0.019). Stratified by ethnicity showed a significant association in Caucasian women, but not among Asian and mixed populations. This meta-analysis confirms that CXCL12 rs1801157 polymorphism is related to breast cancer risk, especially among Caucasian women. However, well-designed large-scale studies are required to further evaluate the results.


Assuntos
Neoplasias da Mama , Quimiocina CXCL12 , Feminino , Humanos , Asiático , Neoplasias da Mama/genética , Estudos de Casos e Controles , Quimiocina CXCL12/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Fatores de Risco , População Branca
12.
J Prim Health Care ; 16(1): 61-69, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38546777

RESUMO

Introduction In Aotearoa New Zealand (NZ), type 2 diabetes (T2D) is predominantly managed in primary care. Despite established guidelines, patients are often suboptimally managed, with inequitable health outcomes. To date, few NZ studies have evaluated the primary care management of T2D at the time of diagnosis. Aim This study aims to explore patients' the provision of education and delivery of care to patients at the time of diagnosis, which is a crucial time in the disease trajectory. Methods Participants were recruited from a Maori health provider in the Waikato District, and diagnosed with T2D after January 2020. Patients were texted a link to opt into a survey (larger study) and then registered interest by providing contact details for an interview (current study). Semi-structured interviews were conducted and were audio recorded, transcribed, and thematically analysed. Results In total, 11 participants aged 19-65 years completed the interviews (female n = 9 and male n = 20); the comprised Maori (n = 5), NZ European (n = 5) and Asian (n = 1) participants. Three overarching themes were identified, including: (1) ineffective provision of resources and education methods; (2) poor communication from healthcare practitioners; and (3) health system barriers. Discussion Evidently, there are difficulties in primary care diabetes mellitus diagnosis and management. Improvements could include locally relevant resources tailored to patients' experiences and cultural identities. Utilising whanau support and a non-clinical workforce, such as health navigators/kaiawhina, will drastically address current workforce issues and assist patient self-management. This will allow improved diagnosis experiences and better health outcomes for patients and whanau.


Assuntos
Diabetes Mellitus Tipo 2 , Autogestão , Feminino , Humanos , Masculino , Diabetes Mellitus Tipo 2/terapia , Diabetes Mellitus Tipo 2/diagnóstico , Povo Maori , Nova Zelândia , Atenção Primária à Saúde , Pesquisa Qualitativa , População Branca , Povo Asiático , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso
13.
Psychol Sci ; 35(4): 415-434, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38507261

RESUMO

Four preregistered experiments (N = 4,307) explored whether anti-Christian bias claims can discreetly signal White allyship among Christian American adults. In Experiments 1 and 2, reading about anti-Christian bias led White, but not Black, Christians to perceive more anti-White bias. Experiments 3 and 4 demonstrate the connection between Christian and White can be leveraged by politicians in the form of a racial dog whistle. In Experiment 3, White Christians perceived a politician concerned about anti-Christian bias as caring more about anti-White bias and more willing to fight for White people (relative to a control). This politician was also perceived as less offensive than a politician concerned about anti-White bias. In Experiment 4, Black Christians perceived a politician concerned about anti-Christian bias as less offensive than one concerned about anti-White bias yet still unlikely to fight for Black people. Results suggest "anti-Christian bias" can provide a relatively palatable way to signal allegiance to White people.


Assuntos
Racismo , Brancos , Adulto , Humanos , Cães , Estados Unidos , Animais , População Branca , Viés
15.
Soc Sci Med ; 347: 116724, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38458127

RESUMO

Structural racism generates racial inequities in U.S. primary education, including segregated schools, inequitable funding and resources, racial disparities in discipline and achievement, and hostile racial climates, which are risk factors for adverse youth health and development. Black youth are disproportionately exposed to adverse school contexts that may become biologically embedded via stress-mediated epigenetic pathways. This study examined whether childhood exposure to adverse school contexts is associated with changes in epigenetic aging during adolescent development. DNA methylation-based epigenetic clocks were calculated from saliva samples at ages 9 and 15 among Black (n = 774) and White (n = 287) youth in the Future of Families and Child Wellbeing Study (2009-2015). We performed latent class analyses to identify race-specific primary school contexts using administrative data on segregation, discipline, achievement, resources, economic disadvantage, and racial harassment. We then estimated change in epigenetic age acceleration from childhood to adolescence across school typologies using GrimAge, PhenoAge, and DunedinPACE epigenetic clocks. Three distinct school contexts were identified for Black youth: segregated and highly-disadvantaged (17.0%), segregated and moderately-disadvantaged (52.1%), and integrated and moderately-disadvantaged (30.8%). Two school contexts emerged for White youth: integrated and unequal (46.5%) and predominantly White & advantaged (53.5%). At age 15, Black youth who attended segregated and highly-disadvantaged primary schools experienced increases in their speed of epigenetic aging with GrimAge and DunedinPACE. Slowed epigenetic aging with GrimAge was observed for Black youth who attended integrated and moderately-disadvantaged schools. School contexts were not associated with changes in epigenetic age acceleration for White youth. Our findings suggest that manifestations of structural racism in primary school contexts are associated with early-life epigenetic age acceleration and may forecast future health inequities.


Assuntos
Racismo , Racismo Sistêmico , Criança , Humanos , Adolescente , Brancos , Negro ou Afro-Americano , População Branca , Instituições Acadêmicas , Epigênese Genética
16.
Front Public Health ; 12: 1345442, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38515598

RESUMO

Objective: We sought to examine trends in diagnosed behavioral health (BH) conditions [mental health (MH) disorders or substance use disorders (SUD)] among pregnant and postpartum individuals between 2008-2020. We then explored the relationship between BH conditions and race/ethnicity, acknowledging race/ethnicity as a social construct that influences health disparities. Methods: This study included delivering individuals, aged 15-44 years, and continuously enrolled in a single commercial health insurance plan for 1 year before and 1 year following delivery between 2008-2020. We used BH conditions as our outcome based on relevant ICD 9/10 codes documented during pregnancy or the postpartum year. Results: In adjusted analyses, white individuals experienced the highest rates of BH conditions, followed by Black, Hispanic, and Asian individuals, respectively. Asian individuals had the largest increase in BH rates, increasing 292%. White individuals had the smallest increase of 192%. The trend remained unchanged even after adjusting for age and Bateman comorbidity score, the trend remained unchanged. Conclusions: The prevalence of diagnosed BH conditions among individuals in the perinatal and postpartum periods increased over time. As national efforts continue to work toward improving perinatal BH, solutions must incorporate the needs of diverse populations to avert preventable morbidity and mortality.


Assuntos
Etnicidade , Hispânico ou Latino , Gravidez , Feminino , Humanos , População Branca , Morbidade , População Negra
17.
Hum Genet ; 143(3): 423-435, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38519595

RESUMO

Meniere disease is a complex inner ear disorder with significant familial aggregation. A differential prevalence of familial MD (FMD) has been reported, being 9-10% in Europeans compared to 6% in East Asians. A broad genetic heterogeneity in FMD has been described, OTOG being the most common mutated gene, with a compound heterozygous recessive inheritance. We hypothesize that an OTOG-related founder effect may explain the higher prevalence of FMD in the European population. Therefore, the present study aimed to compare the allele frequency (AF) and distribution of OTOG rare variants across different populations. For this purpose, the coding regions with high constraint (low density of rare variants) were retrieved in the OTOG coding sequence in Non-Finnish European (NFE).. Missense variants (AF < 0.01) were selected from a 100 FMD patient cohort, and their population AF was annotated using gnomAD v2.1. A linkage analysis was performed, and odds ratios were calculated to compare AF between NFE and other populations. Thirteen rare missense variants were observed in 13 FMD patients, with 2 variants (rs61978648 and rs61736002) shared by 5 individuals and another variant (rs117315845) shared by two individuals. The results confirm the observed enrichment of OTOG rare missense variants in FMD. Furthermore, eight variants were enriched in the NFE population, and six of them were in constrained regions. Structural modeling predicts five missense variants that could alter the otogelin stability. We conclude that several variants reported in FMD are in constraint regions, and they may have a founder effect and explain the burden of FMD in the European population.


Assuntos
Frequência do Gene , Doença de Meniere , Mutação de Sentido Incorreto , População Branca , Humanos , Doença de Meniere/genética , Doença de Meniere/epidemiologia , Feminino , Prevalência , Masculino , População Branca/genética , Europa (Continente)/epidemiologia , Predisposição Genética para Doença , Adulto , Pessoa de Meia-Idade , Ligação Genética , Efeito Fundador
18.
Hypertension ; 81(5): 1167-1177, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38497230

RESUMO

BACKGROUND: The mTOR (mechanistic target of rapamycin) is an essential regulator of fundamental biological processes. mTOR forms 2 distinct complexes, mTORC1 (mTOR complex 1) when it binds with RAPTOR (Regulatory-associated Protein of mTOR) and mTORC2 (mTOR complex 2) when it associates with RICTOR (Rapamycin-insesitive companion of mTOR). Due to the previous link between the mTOR pathway, aldosterone, and blood pressure (BP), we anticipated that variants in the mTOR complex might be associated with salt-sensitive BP. METHODS: BP and other parameters were assessed after a one-week liberal Na+ (200 mmol/d) and a one-week restricted Na+ (10 mmol/d) diet in 608 White subjects from the Hypertensive Pathotype cohort, single-nucleotide variants in MTOR, RPTOR, and RICTOR genes were obtained for candidate genes analyses. RESULTS: The analysis revealed a significant association between a single nucleotide variants within the RPTOR gene and BP. Individuals carrying the RPTOR rs9901846 homozygous risk allele (AA) and heterozygous risk allele (GA) exhibited a 5 mm Hg increase in systolic BP on a liberal diet compared with nonrisk allele individuals (GG), but only in women. This single nucleotide variants effect was more pronounced on the restricted diet and present in both sexes, with AA carriers having a 9 mm Hg increase and GA carriers having a 5 mm Hg increase in systolic BP compared with GG. Interestingly, there were no significant associations between MTOR or RICTOR gene variants and BP. CONCLUSIONS: The RPTOR gene variation is associated with elevated BP in White participants, regardless of salt intake, specifically in females.


Assuntos
Pressão Sanguínea , Hipertensão , Proteína Regulatória Associada a mTOR , Cloreto de Sódio na Dieta , Feminino , Humanos , Masculino , Proteínas de Transporte/genética , Hipertensão/genética , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Alvo Mecanístico do Complexo 2 de Rapamicina/metabolismo , Nucleotídeos/metabolismo , Proteína Companheira de mTOR Insensível à Rapamicina/metabolismo , Proteína Regulatória Associada a mTOR/genética , Proteína Regulatória Associada a mTOR/metabolismo , Sirolimo , Cloreto de Sódio na Dieta/metabolismo , Serina-Treonina Quinases TOR/metabolismo , População Branca
19.
JAMA ; 331(16): 1379-1386, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38526480

RESUMO

Importance: Barriers to heart transplant must be overcome prior to listing. It is unclear why Black men and women remain less likely to receive a heart transplant after listing than White men and women. Objective: To evaluate whether race or gender of a heart transplant candidate (ie, patient on the transplant waiting list) is associated with the probability of a donor heart being accepted by the transplant center team with each offer. Design, Setting, and Participants: This cohort study used the United Network for Organ Sharing datasets to identify organ acceptance with each offer for US non-Hispanic Black (hereafter, Black) and non-Hispanic White (hereafter, White) adults listed for heart transplant from October 18, 2018, through March 31, 2023. Exposures: Black or White race and gender (men, women) of a heart transplant candidate. Main Outcomes and Measures: The main outcome was heart offer acceptance by the transplant center team. The number of offers to acceptance was assessed using discrete time-to-event analyses, nonparametrically (stratified by race and gender) and parametrically. The hazard probability of offer acceptance for each offer was modeled using generalized linear mixed models adjusted for candidate-, donor-, and offer-level variables. Results: Among 159 177 heart offers with 13 760 donors, there were 14 890 candidates listed for heart transplant; 30.9% were Black, 69.1% were White, 73.6% were men, and 26.4% were women. The cumulative incidence of offer acceptance was highest for White women followed by Black women, White men, and Black men (P < .001). Odds of acceptance were less for Black candidates than for White candidates for the first offer (odds ratio [OR], 0.76; 95% CI, 0.69-0.84) through the 16th offer. Odds of acceptance were higher for women than for men for the first offer (OR, 1.53; 95% CI, 1.39-1.68) through the sixth offer and were lower for the 10th through 31st offers. Conclusions and Relevance: The cumulative incidence of heart offer acceptance by a transplant center team was consistently lower for Black candidates than for White candidates of the same gender and higher for women than for men. These disparities persisted after adjusting for candidate-, donor-, and offer-level variables, possibly suggesting racial and gender bias in the decision-making process. Further investigation of site-level decision-making may reveal strategies for equitable donor heart acceptance.


Assuntos
Negro ou Afro-Americano , Transplante de Coração , Doadores de Tecidos , Listas de Espera , População Branca , Humanos , Feminino , Masculino , População Branca/estatística & dados numéricos , Pessoa de Meia-Idade , Fatores Sexuais , Estados Unidos , Adulto , Estudos de Coortes , Obtenção de Tecidos e Órgãos/estatística & dados numéricos
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