Abstract 164: CYP17A1 Variant is Associated with Blood Pressure Reactivity to a Mental but not a Physical Challenge in Male Adolescents and May Be an Early Marker of Hypertension Risk

Individuals who exhibit exaggerated blood pressure (BP) reactivity to physical and mental challenges at a young age are at increased risk of developing hypertension in adulthood. Hypertension is a complex genetic trait that is more prevalent in men than women during reproductive age. CYP17A1 is one of the best-established gene loci of hypertension. It encodes a key enzyme in the steroidogenic pathway that produces mineralocorticoids, glucocorticoids, androgens, and estrogens; as such, it may influence BP reactivity in a sex-specific manner. Here, we investigated whether CYP17A1 is associated with BP reactivity to physical and mental challenges in adolescence. In 285 male and 311 female adolescents (age 12-18 years), we measured systolic BP (SBP) and diastolic BP (DBP) beat-by-beat during a 52-minute protocol, which included a physical (10-min standing) and mental (2-min math test) challenge and we genotyped 8 tagging single nucleotide polymorphisms (SNPs) that covered the entire region of CYP17A1. Genotype-phenotype association tests were performed separately in males and females, while adjusting for age, height and initial BP. Our results showed that 6 SNPs were associated with higher SBP and DBP reactivity (p=0.003-0.0001), but only in response to mental stress and only in boys. At rs619824 , minor allele homozygotes differed from major allele homozygotes by 8.7 mm Hg of SBP (p=3x10-4) and 4.8 mm Hg of DBP (p=1x10-4) in boys, and the two groups varied only by 2.0 mm Hg of SBP (p=0.31) and 0.9 mm Hg of DBP (p=0.42) in girls. These results suggest that CYP17A1 may contribute to the development of hypertension through the regulation of the stress response and that, at least in adolescence, this effect appears to be present in males but not in females.