Abstract 1788: Assessment of Genetic Risk for Hypertension in Japanese Individuals
Introduction. Hypertension is a major risk factor for myocardial infarction and ischemic stroke. Although genetic epidemiological studies have suggested that several genetic variants increase the risk for hypertension, the genes that underlie genetic susceptibility to this condition remain to be identified.
Hypothesis. We assessed the hypothesis that genetic variants that confer susceptibility to myocardial infarction or ischemic stroke might contribute to the development of hypertension.
Methods. A total of 5734 Japanese individuals from two independent populations was examined: Subject panel A comprised 2066 individuals with hypertension and 824 controls; subject panel B comprised 834 cases and 2010 controls. The 150 polymorphisms examined in the present study were selected by genome-wide association studies of myocardial infarction and ischemic stroke with the use of the GeneChip Human Mapping 500K Array Set (Affymetrix).
Results and Conclusions. On the basis of comparisons of genotype distributions by the chi-square test, 10 polymorphisms were significantly (P <0.05) associated with the prevalence of hypertension in subject panel A. To validate the relations, these polymorphisms were examined in subject panel B. The A→G polymorphism (rs645106) of the sidekick homolog 1 gene (SDK1) and the C→G polymorphism (rs12078839) of the RAB GTPase activating protein 1-like gene (RABGAP1L) were significantly associated with hypertension in subject panel B. Multivariable logistic regression analysis with adjustment for covariates, as well as a stepwise forward selection procedure revealed that the A→G polymorphism of SDK1 (P < 0.015; odds ratio, 0.74) was significantly associated with hypertension in subject panel A. Similar analyses revealed that the A→G polymorphism of SDK1 (P =0.014; odds ratio, 0.56) and the C→G polymorphism of RABGAP1L (P = 0.0069; odds ratio, 1.39) were significantly associated with hypertension in subject panel B. In conclusion, the A→G polymorphism of SDK1 was significantly associated with hypertension in both subject panels A and B, with the G allele protecting against this condition. Determination of genotype for this polymorphism may prove informative for assessment of the genetic risk for hypertension.