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Endocrine Abstracts (2018) 56 OC10.3 | DOI: 10.1530/endoabs.56.OC10.3

1Section on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA; 2Division of Endocrinology, Diabetes, and Metabolism, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; 3Johns Hopkins Community Physicians at Suburban Hospital, Bethesda, Maryland, USA; 4Carey Johns Hopkins University Business School, Baltimore, Maryland, USA; 5National Human Genome Research Institute (NHGRI), Genomics of Metabolic, Cardiovascular and Inflammatory Disease Branch, Cardiovascular Section, Bethesda, Maryland, USA.

Context: Hypertension is one of the most preventable risk factors for cardiovascular disease and death. Up to 42.1% of non-Hispanic African-American subjects have hypertension. We recently found that germline ARMC5 variants may play a role in primary aldosteronism, particularly in African-Americans.

Objective: We investigated a cohort of participants in the Minority Health Genomics and Translational Research Bio-Repository Database (MH-GRID) study. We hypothesized a direct association between ARMC5 variants and increased risk of hypertension in African-Americans.

Methods: MH-GRID Whole Exome Sequencing data of 1377 African-American subjects was analyzed. Cases are individuals on two or more anti-hypertensive medications of different classes, including a diuretic and controls are individuals with optimal blood pressure (BP ≤ 120/80 mmHg) and normal kidney function (eGFR > 90 ml/min). Target single-variant and gene-based association analyses were carried out using the ARMC5 locus information from genome-build GRCh37: chromosome =16, start position =3146941 and end position =31478484. Single-variant analysis of common variants (minor allele frequency, MAF ≥ 0.05) within ARMC5 was conducted in PLINK 1.9. Gene-based analysis combining, common, low frequency (MAF ≥ 0.01 and < 0.05) and rare variants (MAF < 0.01) within ARMC5 was carried out using the optimal unified kernel association test. The analyses were adjusted for age, gender, HDL, LDL, smoking and African-European admixture.

Results: 44 SNPs within ARMC5 (3 common, 4 low frequency and 37 rare variants) were considered for analysis. An ARMC5 variant common in MH-GRID (rs116201073, MAF=0.07) reached nominal significance (P=0.044) and odds ratio (OR) =0.7, suggesting a protective effect for this variant. In the gene-based analysis, a set of 16 rare variants was significantly associated with hypertension (adjusted P=0.0402). A total of 17 variants (the 16 rare variants and rs116201073) were also significantly associated with hypertension at a lower p-value (adjusted P=0.0121).

Conclusions: We identified one common SNP of the ARMC5 gene that was associated with risk of hypertension in African Americans and a set of 16 rare variants associated with hypertension in African Americans. These results extend our previous report of increased germline ARMC5 variants that may be linked to severe hypertension in African-Americans, perhaps due to low-renin hypertension. Further genetic and molecular studies are needed to confirm and complement these findings.

Volume 56

20th European Congress of Endocrinology

Barcelona, Spain
19 May 2018 - 22 May 2018

European Society of Endocrinology 

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