Human Genetics, 2014, 01, 311─319

Male-specific genetic effect on hypertension and metabolic disorders

Heo SG, Hwang JY, Uhmn S, Go MJ, Oh B, Lee JY, Park JW

Abstract

Genetic risk factors for hypertension may have age or gender specificity and pleiotropic effects.
This study aims to measure the risk of genetic and non-genetic factors in the occurrence of hypertension and related diseases, with consideration of potential confounding factors and age-gender stratification.
A discovery set of 352,228 genotyped plus 1.8 million imputed single-nucleotide polymorphisms were analyzed for 2,886 hypertensive cases and 3,440 healthy controls obtained from two community-based cohorts in Korea, and selected gene variants were replicated in the Health Examinee cohort (665 cases and 1,285 controls).
Genomewide association analyses were conducted in 12 groups stratified by age and gender after adjusting for potential covariates under three genetic models. Age, rural area residence, body mass index, family history of hypertension, male gender, current alcohol drinking status, and current smoking status were significantly associated with hypertension (P = 4 × 10E-0151 to 0.011).
Five gene variants, rs11066280 (C12orf51), rs12229654 and rs3782889 (MYL2), rs2072134 (OAS3), rs2093395 (TREML2), and rs17249754 (ATP2B1), were found to be associated with hypertension mostly in men (P = 4.76E？014 to 4.46E？07 in the joint analysis);
three SNPs (rs11066280, rs12229654, and rs3782889) remained significant after Bonferroni correction in an independent population.
Three gene variants, rs12229654, rs17249754, and rs11066280, were significantly associated with metabolic disorders such as hyperlipidemia and diabetes (P = 0.00071 to 0.0097, respectively).
Careful consideration of the potential confounding effects in future genomewide association studies is necessary to uncover the genetic underpinnings of complex diseases

• ISBN or ISSN: 0340-6717

• 본 연구는 질병관리본부 연구개발과제(과제번호 2012-N73002-00) 연구비를 지원받아 수행되었습니다.
• This research was supported by a fund(code 2012-N73002-00) by Research of Korea Centers for Disease Control and Prevention.