Association of polymorphisms of CELSR1 and chromosome 3q28 with hypertension in community-dwelling Japanese individuals

Abstract

Purpose: We previously showed that rs6007897 (C→T, Ala2268Thr) of the cadherin, EGF LAG seven-pass G-type receptor 1 gene (CELSR1) was significantly associated with ischemic stroke in Japanese individuals by a Genome-Wide Association Study (GWAS). We also identified rs9846911 (A→G) at chromosome 3q28 as a susceptibility locus for chronic kidney disease in Japanese individuals by a GWAS. Given that hypertension is a major risk factor for both ischemic stroke and chronic kidney disease, we hypothesized that the association of rs6007897 of CELSR1 with ischemic stroke or of rs9846911 at 3q28 with chronic kidney disease might be attributable, at least in part, to their effects on genetic susceptibility to hypertension. The purpose of the present study was to examine a possible association of rs6007897 of CELSR1 or rs9846911 at 3q28 with hypertension in community-dwelling Japanese individuals. Methods: Study subjects comprised 5959 community-dwelling individuals (1670 subjects with hypertension, 4289 controls) who were recruited to a population-based cohort study in Inabe City, Japan between 2003 and 2012. The Inabe Study is a longitudinal genetic epidemiological study of atherosclerotic, cardiovascular, and metabolic diseases. The subjects are recruited from individuals who visited the health care center of Inabe General Hospital for an annual health checkup. The subjects with hypertension either had a systolic Blood Pressure (BP) of ≥140 mmHg or diastolic BP of ≥90 mmHg (or both) or had taken antihypertensive medication. The control individuals had systolic BP of <140 mmHg and diastolic BP of <90 mmHg and no history of hypertension or of taking antihypertensive medication. Results: Comparisons of allele frequencies by the chi-square test revealed that rs6007897 of CELSR1 (P = 0.0280) and rs9846911 at 3q28 (P = 0.0171) were significantly associated with hypertension. Multivariable logistic regression analysis with adjustment for age, sex, body mass index, smoking status, the serum concentration of creatinine, and the prevalence of diabetes mellitus and dyslipidemia revealed that rs6007897 (P = 0.0308; recessive model; odds ratio, 1.56) and rs9846911 (P = 0.0353; dominant model; odds ratio, 1.22) were significantly associated with hypertension with the T allele of rs6007897 and the G allele rs984691 representing risk factors for hypertension. Conclusions: CELSR1 and 3q28 may be susceptible loci for hypertension in Japanese individuals. Determination of genotypes for these polymorphisms may prove informative for assessment of the genetic risk for hypertension in the Japanese population.