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Implications of Polymorphisms in the BCKDK and GATA-4 Gene Regions on Stable Warfarin Dose in African Americans.
Bargal, SA, Kight, JN, Augusto de Oliveira, F, Shahin, MH, Langaee, T, Gong, Y, Hamadeh, IS, Cooper-DeHoff, RM, Cavallari, LH
Clinical and translational science. 2021;(2):492-496
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Abstract
VKORC1 and CYP2C9 genotypes explain less variability in warfarin dose requirements in African Americans compared with Europeans. Variants in BCKDK and GATA-4 gene regions, purported to regulate VKORC1 and CYP2C9 expression, have been shown to play an important role in warfarin dose requirements in Europeans and Asians, respectively. We sought to determine whether rs56314408 near BCKDK or GATA-4 rs2645400 influence warfarin dose requirements in 200 African Americans. Unlike the strong linkage disequilibrium (LD) between rs56314408 and VKORC1 rs9923231 in Europeans, they were not in LD in African Americans. No associations were found on univariate analysis. On multivariable analysis, rs56314408 was associated (P = 0.027) with dose in a regression model excluding VKORC1 rs9923231, and GATA-4 rs2645400 was associated (P = 0.032) with dose in a model excluding CYP2C (CYP2C9*2, *3, *5, *6, *8, and *11, CYP2C rs12777823) variants. Neither variant contributed to dose in the model that included both VKORC1 rs9923231 and CYP2C variants. Our results do not support contributions of the studied variants to warfarin dose requirements in African Americans. However, they illustrate the value of studies in African descent populations, who have low LD in their genome, in teasing out genetic variation underlying drug response associations. They also emphasize the importance of confirming associations in persons of African ancestry.
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The Association of ARMC5 with the Renin-Angiotensin-Aldosterone System, Blood Pressure, and Glycemia in African Americans.
Joseph, JJ, Zhou, X, Zilbermint, M, Stratakis, CA, Faucz, FR, Lodish, MB, Berthon, A, Wilson, JG, Hsueh, WA, Golden, SH, et al
The Journal of clinical endocrinology and metabolism. 2020;(8):2625-33
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Abstract
CONTEXT Armadillo repeat containing 5 (ARMC5) on chromosome 16 is an adrenal gland tumor suppressor gene associated with primary aldosteronism, especially among African Americans (AAs). We examined the association of ARMC5 variants with aldosterone, plasma renin activity (PRA), blood pressure, glucose, and glycosylated hemoglobin A1c (HbA1c) in community-dwelling AAs. METHODS The Jackson Heart Study is a prospective cardiovascular cohort study in AAs with baseline data collection from 2000 to 2004. Kernel machine method was used to perform a single joint test to analyze for an overall association between the phenotypes of interest (aldosterone, PRA, systolic and diastolic blood pressure [SBP, DBP], glucose, and HbA1c) and the ARMC5 single nucleotide variants (SNVs) adjusted for age, sex, BMI, and medications; followed by Baysian Lasso methodology to identify sets of SNVs in terms of associated haplotypes with specific phenotypes. RESULTS Among 3223 participants (62% female; mean age 55.6 (SD ± 12.8) years), the average SBP and DBP were 127 and 76 mmHg, respectively. The average fasting plasma glucose and HbA1c were 101 mg/dL and 6.0%, respectively. ARMC5 variants were associated with all 6 phenotypes. Haplotype TCGCC (ch16:31476015-31476093) was negatively associated, whereas haplotype CCCCTTGCG (ch16:31477195-31477460) was positively associated with SBP, DBP, and glucose. Haplotypes GGACG (ch16:31477790-31478013) and ACGCG (ch16:31477834-31478113) were negatively associated with aldosterone and positively associated with HbA1c and glucose, respectively. Haplotype GCGCGAGC (ch16:31471193-ch16:31473597(rs114871627) was positively associated with PRA and negatively associated with HbA1c. CONCLUSIONS ARMC5 variants are associated with aldosterone, PRA, blood pressure, fasting glucose, and HbA1c in community-dwelling AAs, suggesting that germline mutations in ARMC5 may underlie cardiometabolic disease in AAs.
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Association between asthma, obesity, and health behaviors in African American youth.
Nagy, MR, McGlumphy, KC, Dopp, R, Lewis, TC, Hasson, RE
The Journal of asthma : official journal of the Association for the Care of Asthma. 2020;(4):410-420
Abstract
Background: There is a clear relationship between obesity and asthma, with obesity recognized as a risk factor for asthma. There is mounting evidence, however, that asthma may predict obesity risk via behavioral pathways. Objectives: The purpose of this study was to assess the cross-sectional relationships between asthma, body mass index (BMI) percentile, and behavioral factors including caloric intake, dietary inflammatory index, moderate-vigorous physical activity (MVPA), and sedentary time (SED) among African American adolescents. Methods: A community-based sample of 195 African American youth (ages 11-18 years) were included in this analysis. Asthma status was based on self-report using the International Study of Asthma and Allergies in Children's Phase Three questionnaire. MVPA and SED were measured via accelerometry, and caloric intake and dietary inflammatory index were evaluated with the Food Frequency Questionnaire. Weight status was assessed via BMI percentile using measured weight, height, and CDC growth charts. Results: Adolescents with a history of asthma were significantly more overweight (62% vs. 43%, p = 0.04) and consumed a higher inflammatory diet (1.6 ± 0.3 vs. 1.0 ± 0.2, p = 0.02) than their peers who never had asthma. After adjusting for all covariates, activity and dietary variables, odds ratio analysis revealed adolescents who reported ever having asthma were 3.1 ± 1.5 times as likely to be overweight or obese than adolescents with no asthma history (p = 0.02). Conclusions: Presence of asthma history was associated with increased obesity risk in African American adolescents, independent of behavioral factors. Longitudinal studies are needed to better understand the relationship between asthma and obesity in African American adolescents.
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Genomewide Gene-by-Sex Interaction Scans Identify ADGRV1 for Sex Differences in Opioid Dependent African Americans.
Yang, BZ, Zhou, H, Cheng, Z, Kranzler, HR, Gelernter, J
Scientific reports. 2019;(1):18070
Abstract
Sex differences in opioid dependence (OD) are genetically influenced. We conducted genomewide gene-by-sex interaction scans for the DSM-IV diagnosis of OD in 8,387 African-American (AA) or European-American subjects (43.6% women; 4,715 OD subjects). Among AAs, 9 SNPs were genome-wide significant at ADGRV1 (adhesion G-protein-coupled receptor V1, lead-SNP rs2366929*(C/T), p = 1.5 × 10-9) for sex-different risk of OD, with the rs2366929*C-allele increasing OD risk only for men. The top co-expressions in brain were between ADGRV1 and GRIK2 in substantia nigra and medullary inferior olivary nucleus, and between ADGRV1 and EFHC2 in frontal cortex and putamen. Significant sex-differential ADGRV1 expression from GTEx was detected in breast (Bonferroni-corrected-p < 0.002) and in heart (p < 0.0125), with nominal significance identified in brain, thyroid, lung, and stomach (p < 0.05). ADGRV1 co-expression and disease-enrichment analysis identifying the top 10 diseases showed strikingly sexually dimorphic risks. The enrichment and transcriptome analyses provided convergent support that ADGRV1 exerts a sex-different effect on OD risk. This is the first study to identify genetic variants contributing to sex differences in OD. It shows that ADGRV1 contributes to OD risk only in AA men, a finding that warrants further study.
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Stress, Resilience, and Cardiovascular Disease Risk Among Black Women.
Felix, AS, Lehman, A, Nolan, TS, Sealy-Jefferson, S, Breathett, K, Hood, DB, Addison, D, Anderson, CM, Cené, CW, Warren, BJ, et al
Circulation. Cardiovascular quality and outcomes. 2019;(4):e005284
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Abstract
BACKGROUND Empirical data on the link between stress and cardiovascular disease (CVD) risk among black women is limited. We examined associations of stressful life events and social strain with incident CVD among black women and tested for effect modification by resilience. METHODS AND RESULTS Our analysis included 10 785 black women enrolled in the Women's Health Initiative Observational Study and Clinical Trials cohort. Participants were followed for CVD for up to 23 years (mean, 12.5). Multivariable Cox regression was used to estimate hazard ratios and 95% CIs for associations between stress-related exposures and incident CVD. We included interactions between follow-up time (age) and stressful life events because of evidence of nonproportional hazards. Effect modification by resilience was examined in the sub-cohort of 2765 women with resilience and stressful life events measures. Higher stressful life events were associated with incident CVD at ages 55 (hazard ratio for highest versus lowest quartile=1.80; 95% CI, 1.27-2.54) and 65 (hazard ratio for highest versus lowest quartile=1.40; 95% CI, 1.16-1.68), but not at older ages. Adjustment for CVD risk factors attenuated these associations. Similar associations were observed for social strain. In the sub-cohort of women with updated stressful life events and resilience measures, higher stressful life events were associated with incident CVD in multivariable-adjusted models (hazard ratio=1.61; 95% CI, 1.04-2.51). Resilience did not modify this association nor was resilience independently associated with incident CVD. CONCLUSIONS In this cohort of older black women, recent reports of stressful life events were related to incident CVD. Resilience was unrelated to incident CVD. CLINICAL TRIALS REGISTRATION URL: https://www.clinicaltrials.gov . Unique identifier: NCT00000611.
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Protein Intake and Long-term Change in Glomerular Filtration Rate in the Jackson Heart Study.
Malhotra, R, Lipworth, L, Cavanaugh, KL, Young, BA, Tucker, KL, Carithers, TC, Taylor, HA, Correa, A, Kabagambe, EK, Ikizler, TA
Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation. 2018;(4):245-250
Abstract
OBJECTIVE Dietary protein intake could have deleterious renal effects in populations at risk for chronic kidney disease. Here, we examined whether higher protein intake (≥80th percentile of energy from protein) is associated with decline in kidney function and whether this decline varies by diabetes status. DESIGN Observational cohort study. SUBJECTS AND SETTINGS Participants were African-Americans (n = 5,301), who enrolled in the Jackson Heart Study between 2000 and 2004. METHODS Dietary intake was assessed using a validated food-frequency questionnaire at baseline, and serum creatinine was measured at baseline (visit 1) and 8 years later (visit 3). Estimated glomerular filtration rates (eGFRs) at baseline and follow-up were computed using the chronic kidney disease epidemiology collaboration equation. MAIN OUTCOME MEASURE The change in eGFR was computed by subtracting eGFR at visit 1 from that at visit 3. RESULTS Of 3,165 participants with complete data, 64% were women, 57% had hypertension, and 19% had diabetes. The median (25th, 75th percentile) percent energy intake from protein was 14.3 (12.4, 16.4), comparable to that reported for the general US population (15% of energy). During a median (25th, 75th percentile) follow-up of 8.0 (7.4, 8.3) years, eGFR declined by 10.5% from a mean (SD) of 97.4 (17.5) to 86.9 (21.3) mL/min/1.73 m2. In the fully adjusted model, consumption of protein as percent of energy intake in lowest and highest quintiles was associated with decline in eGFR among diabetic subjects. The analysis of variance with a robust variance estimator was used to determine whether long-term change in eGFR significantly varies by protein intake. CONCLUSIONS Our results show that, among African-Americans with diabetes, higher protein intake as a percent of total energy intake is positively associated with greater decline in eGFR in analyses that accounted for risk factors for kidney disease.
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An Exploration of the Determinants of Gestational Weight Gain in African American Women: Genetic Factors and Energy Expenditure.
Meng, Y, Groth, SW, Stewart, P, Smith, JA
Biological research for nursing. 2018;(2):118-125
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Abstract
BACKGROUND Excessive gestational weight gain (GWG) has a long-term impact on women's body weight and contributes to the development of obesity in the mother and her child. Many risk factors for GWG have been identified, but to date, only 6-33.8% of the variance in GWG has been explained. The purpose of this study was to evaluate the overall variance of GWG that can be explained by including weight-adjusted resting metabolic rate (aRMR) and a genetic risk score constructed on obesity-related genes in addition to sociodemographic and lifestyle factors. METHODS In this observational study involving 55 African American women, data collected/measured during pregnancy included sociodemographic factors, medical information, lifestyle factors, aRMR, and seven obesity-related genes. Multivariable linear regression was performed to evaluate the variance in GWG explained by the potential risk factors listed above. RESULTS The mean GWG was 15 kg (±7.5 kg), and 63.6% of women gained more than the Institute of Medicine's GWG recommendations. The final regression model explained 53.3% of the variance in GWG. Higher genetic risk score, lower aRMR, and higher dietary intake of total energy and percentage of fat were significantly associated with increased GWG ( p < .05). These factors explained 18% additional variance in GWG over that explained by significant sociodemographic and lifestyle factors in the analysis (i.e., maternal age, prepregnancy body mass index, parity, illegal drug use, and education). CONCLUSION Overall, our results indicate that the genetic risk score, aRMR, and dietary intake have a substantial impact on GWG in African American women.
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Association of APOL1 With Heart Failure With Preserved Ejection Fraction in Postmenopausal African American Women.
Franceschini, N, Kopp, JB, Barac, A, Martin, LW, Li, Y, Qian, H, Reiner, AP, Pollak, M, Wallace, RB, Rosamond, WD, et al
JAMA cardiology. 2018;(8):712-720
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IMPORTANCE APOL1 genotypes are associated with kidney diseases in African American individuals and may influence cardiovascular disease and mortality risk, but findings have been inconsistent. OBJECTIVE To discern whether high-risk APOL1 genotypes are associated with cardiovascular disease and stroke in postmenopausal African American women, who are at high risk for these outcomes. DESIGN, SETTING, AND PARTICIPANTS The Women's Health Initiative is a prospective cohort that enrolled 161 838 postmenopausal women into clinical trials and an observational study between 1993 and 1998. This study includes 11 137 African American women participants who had a clinical event from enrollment to June 2014. Data analyses were completed from January 2017 to August 2017. EXPOSURES The variants of APOL1 were genotyped or imputed from whole-exome sequencing. MAIN OUTCOMES AND MEASURES Incident coronary heart disease, stroke and heart failure subtypes, and overall and cause-specific mortality were adjudicated from hospital records and death certificates. Estimated incidence rates were determined for each outcome and hazard ratios (HR) and 95% CIs for the associations of APOL1 groups with outcomes. RESULTS The mean (SD) age of participants was 61.7 (7.1) years. Carriers of high-risk APOL1 variants (n = 1370; 12.3%) had higher prevalence of hypertension, use of cholesterol-lowering medications, and reduced estimated glomerular filtration rate (eGFR). After a mean (SD) of 11.0 (3.6) years, carriers of high-risk APOL1 variants had a higher incidence rate of hospitalized heart failure with preserved ejection fraction (HFpEF) than low-risk carriers did but showed no differences for other outcomes. In adjusted models, there was a significant 58% increased hazard of hospitalized HFpEF (HR, 1.58 [95% CI, 1.03-2.41]) among carriers of high-risk APOL1 variants compared with carriers of low-risk APOL1 variants. The association with HFpEF was attenuated (HR = 1.50 [95% CI, 0.98-2.30]) and no longer significant when adjusting for baseline eGFR. CONCLUSIONS AND RELEVANCE Status as a carrier of a high-risk APOL1 genotype was associated with HFpEF hospitalization among postmenopausal women, which is partly accounted for by baseline kidney function. These findings do not support an association of high-risk APOL1 genotypes with coronary heart disease, stroke, or mortality in postmenopausal African American women.
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Prospective Association of Physical Activity and Heart Failure Hospitalizations Among Black Adults With Normal Ejection Fraction: The Jackson Heart Study.
Koo, P, Gjelsvik, A, Choudhary, G, Wu, WC, Wang, W, McCool, FD, Eaton, CB
Journal of the American Heart Association. 2017;(9)
Abstract
BACKGROUND Given high rates of obesity, hypertension, and diabetes mellitus, black persons are at risk to develop heart failure. The association of moderate to vigorous physical activity (MVPA) and heart failure in black adults is underresearched. The purpose of this study was to explore whether greater MVPA was associated with lower risk of heart failure hospitalizations (HFHs) among black adults with normal ejection fractions. METHODS AND RESULTS We performed a prospective analysis of 4066 black adults who participated in the Jackson Heart Study and who had physical activity measured, had normal ejection fraction on 2-dimensional echocardiograms, and were followed for 7 years for incident HFH. We used Cox proportional regression analyses adjusted for age, sex, body mass index, smoking status, hypertension, diabetes mellitus, chronic obstructive pulmonary disease, coronary heart disease, atrial fibrillation, and chronic kidney disease and examined effect modification by sex and body mass index. Of the eligible population, 1925 participants, according to the duration of MVPA, had poor health (0 minutes/week), 1332 had intermediate health (1-149 minutes/week), and 809 had ideal health (≥150 minutes/week). There were 168 incident HFHs. MVPA for intermediate and ideal health was associated with decreasing risk of incident HFH (hazard ratio: 0.70 [95% confidence interval, 49-1.00] and 0.35 [95% confidence interval, 0.19-0.64], respectively; Ptrend=0.003). The full model revealed hazard ratios of 0.74 [95% confidence interval, 0.52-1.07] and 0.41 [95% confidence interval, 0.22-0.74], respectively. There was no effect modification between MVPA and body mass index or sex on incident HFH. CONCLUSIONS A dose-response relationship between increasing levels of MVPA and protection from incident HFH was found in black men and women with normal ejection fractions.
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Differences in the Protective Effect of Exclusive Breastfeeding on Child Overweight and Obesity by Mother's Race.
Ehrenthal, DB, Wu, P, Trabulsi, J
Maternal and child health journal. 2016;(9):1971-9
Abstract
Objectives To examine the relationship between infant feeding and risk of child overweight and obesity across race and ethnicity in a diverse community-based cohort. Methods 2172 mother baby dyads were drawn from a prospective cohort constructed using data from electronic medical records linked to birth records. The primary exposure was exclusive breastfeeding at 2 months of age; outcome was BMI Z-score and BMI ≥ 85th percentile (overweight and obese) at 4 years of age. Regression models were adjusted for confounding using covariance balanced propensity score and inverse probability weighting. Results At age 4, exclusively breast fed children had lower BMI Z-score (-0.109, SE = 0.048) and a decreased odds of a BMI ≥ 85th percentile (0.832; 95 % CI 0.792, 0.994), when compared to those exclusively formula-fed or had mixed feeding. Race and ethnicity significantly moderated these associations. Sub-population analysis showed the effect was significant for BMI Z-score (p = 0.0002) and BMI ≥ 85th percentile (p < 0.0001) only for children of NH white mothers. For children of NH black mothers exclusive breastfeeding was not associated with a significant difference in BMI Z-score, however there was an increased odds of overweight or obesity (p = 0.0145). Conclusions The protective effect of breastfeeding against early childhood overweight and obesity may differ by race and ethnicity. This suggests that programs aiming to reduce obesity by increasing rates of breastfeeding may have limited impact for some groups and should be coupled with other racially and ethnically focused efforts to encourage healthy feeding practices in infancy and early childhood.