Deep-Targeted Exon Sequencing Reveals Angiotensinogen (AGT) loci on Chr 1q42.2 Associate with Postexercise Hypotension among Caucasians

Abstract

PURPOSE: We performed a candidate gene association meta-analysis on the blood pressure (BP) response to exercise. Only Angiotensinogen (AGT) rs699 emerged as a promising variant. We used deep-targeted sequencing to determine if Chr 1 AGT-Exon target regions 27648912-27648916 harbored variants associated with the BP response following acute exercise. METHODS: 25 obese (30.7±0.7kg/m2) adults (36% Caucasian; 64% Non-Caucasian) 41.1±2.1yr with prehypertension (139.8±2.0/84.8±1.2mmHg) completed 2 random acute experiments: moderate intensity cycling and control seated rest. Subjects wore an ambulatory BP monitor for the next 9 hours. We performed exon sequencing using the Illumina TruSeq Custom Amplicon kit (Catalog# FC-130-1001, Illumina, San Diego, CA). Variant genotypes were coded as the number of minor alleles (#MA) and selected for further statistical analysis based upon Bonferonni adjusted p<0.05 resulting from time-adjusted linear mixed models accounting for 9 hourly BP measurements for each subject. In further analysis, models were selected using maximum likelihood estimation and Akaike information criterion. AGT rs7079 and rs2067853 had identical genotypic values and exhibited significant relationships with the systolic BP (SBP) change after versus before acute exercise compared to control among Caucasians (unadjusted p= 0.000315); we only report findings for rs7079. RESULTS: SBP changed after versus before exercise compared to control by rs7079: 0#MA -12.9±6.5mmHg (nxt=4x9); 1#MA -3.8±3.9mmHg (nxt=4x9); 2#MA +5.8 mmHg (nxt=1x9). CONCLUSIONS: AGT rs7079 is in linkage disequilibrium with rs699, a variant reported to associate with the BP response to exercise. Chr 1q42.2, containing AGT rs7079, rs2067853, and rs699, may be a region that affects the BP response to exercise.