Dataset Information

ARMC 5 Variants and Risk of Hypertension in Blacks: MH- GRID Study.

ABSTRACT: Background We recently found that ARMC 5 variants may be associated with primary aldosteronism in blacks. We investigated a cohort from the MH - GRID (Minority Health Genomics and Translational Research Bio-Repository Database) and tested the association between ARMC 5 variants and blood pressure in black s. Methods and Results Whole exome sequencing data of 1377 black s were analyzed. Target single-variant and gene-based association analyses of hypertension were performed for ARMC 5, and replicated in a subset of 3015 individuals of African descent from the UK Biobank cohort. Sixteen rare variants were significantly associated with hypertension ( P=0.0402) in the gene-based (optimized sequenced kernel association test) analysis; the 16 and one other, rs116201073, together, showed a strong association ( P=0.0003) with blood pressure in this data set. The presence of the rs116201073 variant was associated with lower blood pressure. We then used human embryonic kidney 293 and adrenocortical H295R cells transfected with an ARMC 5 construct containing rs116201073 (c.*920T>C). The latter was common in both the discovery ( MH - GRID ) and replication ( UK Biobank) data and reached statistical significance ( P=0.044 [odds ratio, 0.7] and P=0.007 [odds ratio, 0.76], respectively). The allele carrying rs116201073 increased levels of ARMC5 mRNA , consistent with its protective effect in the epidemiological data. Conclusions ARMC 5 shows an association with hypertension in black s when rare variants within the gene are considered. We also identified a protective variant of the ARMC 5 gene with an effect on ARMC 5 expression confirmed in vitro. These results extend our previous report of ARMC 5's possible involvement in the determination of blood pressure in blacks.

SUBMITTER: Zilbermint M

PROVIDER: S-EPMC6662143 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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ARMC 5 Variants and Risk of Hypertension in Blacks: MH- GRID Study.

Zilbermint Mihail M Gaye Amadou A Berthon Annabel A Hannah-Shmouni Fady F Faucz Fabio R FR Lodish Maya B MB Davis Adam R AR Gibbons Gary H GH Stratakis Constantine A CA

Journal of the American Heart Association 20190703 14

Background We recently found that ARMC 5 variants may be associated with primary aldosteronism in blacks. We investigated a cohort from the MH - GRID (Minority Health Genomics and Translational Research Bio-Repository Database) and tested the association between ARMC 5 variants and blood pressure in black s. Methods and Results Whole exome sequencing data of 1377 black s were analyzed. Target single-variant and gene-based association analyses of hypertension were performed for ARMC 5, and replic ...[more]

PMID: 31266387

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Project description:BACKGROUND AND OBJECTIVES:The natural history of kidney disease among blacks who carry the APOL1 high-risk variants varies, with only a subgroup progressing to ESRD. We aimed to determine whether the APOL1 risk variants are associated with incident proteinuria in the context of hypertension-attributed CKD, and whether subsequent kidney function decline after the onset of proteinuria differs by APOL1 risk status. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:Using Cox models, we studied the association between APOL1 risk status and incident proteinuria (defined as a doubling of urine protein-to-creatinine ratio to a level ?0.22 g/g creatinine) among African-American Study of Kidney Disease and Hypertension (AASK) trial participants with APOL1 genotyping and without proteinuria at baseline. RESULTS:Of the 480 participants in our study, 82 (17%) had the high-risk genotypes (2 alleles), and 254 (53%) developed proteinuria over a median follow-up of 6.8 years. At baseline, mean eGFR was lower in the APOL1 high-risk group compared with the low-risk group (0 or 1 allele; 49.6 versus 53.2 ml/min per 1.73 m2, respectively; P=0.02), but median proteinuria was similar (0.04 g/g creatinine for both groups; P=0.43). Individuals with the high-risk genotypes were 1.72-fold more likely to develop incident proteinuria compared with those with the low-risk genotypes (95% confidence interval, 1.27 to 2.32), independent of age, sex, ancestry, baseline eGFR, baseline systolic BP, and randomized treatment groups. Although eGFR declined faster after the onset of proteinuria, this rate did not differ significantly by APOL1 risk status. CONCLUSIONS:Among blacks with established moderate CKD, the APOL1 high-risk variants are associated with greater risk of incident proteinuria. After proteinuria onset, kidney function declines more rapidly but does not differ by APOL1 risk status. This suggests that factors that lead to proteinuria, beyond APOL1, may additionally drive CKD progression.

Project description:BackgroundAmong individuals without hypertension based on clinic blood pressure (BP), it is unclear who should be screened for masked hypertension, defined as having hypertension based on out-of-clinic BP. We hypothesized that individuals with a higher 10-year predicted atherosclerotic cardiovascular disease (ASCVD) risk, calculated using the pooled cohort risk equations, have a higher prevalence of masked hypertension.Methods and resultsWe analyzed data from the Jackson Heart Study-a population-based cohort of blacks-to determine the association of predicted ASCVD risk with masked hypertension. The sample included 644 participants, 40 to 79 years of age, with clinic systolic/diastolic BP <140/90 mm Hg, who completed ambulatory BP monitoring, were free of cardiovascular disease, and had data on factors needed to calculate ASCVD risk. Ten-year predicted ASCVD risk was calculated using the pooled cohort risk equations. Any masked hypertension was defined as masked daytime hypertension (mean daytime systolic/diastolic BP ≥135/85 mm Hg), masked nighttime hypertension (mean nighttime systolic/diastolic BP ≥120/70 mm Hg), or masked 24-hour hypertension (mean 24-hour systolic/diastolic BP ≥130/80 mm Hg). The prevalence of any masked hypertension was 54.0%. Compared with participants in the lowest (<5%) predicted ASCVD risk category, multivariable-adjusted prevalence ratios (95% confidence interval) for any masked hypertension were 1.36 (1.03-1.79), 1.62 (1.22-2.16), and 1.91 (1.47-2.48) for those with ASCVD risk of 5% to <7.5%, 7.5% to <10%, and ≥10%, respectively. The C statistic for discriminating between participants with versus without any masked hypertension was 0.681 (95% confidence interval, 0.640-0.723) for ASCVD risk and 0.703 (95% confidence interval, 0.663-0.744) for clinic systolic BP and diastolic BP.ConclusionsHigher ASCVD risk was associated with an increased prevalence of masked hypertension. Although the discrimination of ASCVD risk for masked hypertension was not superior to clinic BP, risk prediction equations may be useful for identifying the subgroup of individuals with both masked hypertension and high predicted ASCVD risk.

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ARMC 5 Variants and Risk of Hypertension in Blacks: MH- GRID Study.

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ARMC 5 Variants and Risk of Hypertension in Blacks: MH- GRID Study.

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