Abstract 2385: Assessment of the Genetic Component of Hypertension
Aims 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 definitively. The purpose of the present study was to identify gene polymorphisms that confer susceptibility to hypertension.
Methods The study population comprised 4853 unrelated Japanese individuals, including 2818 subjects with hypertension (1677 men, 1141 women) and 2035 controls (1011 men, 1024 women). The genotypes for 150 polymorphisms of 128 candidate genes were determined with a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology.
Results Multivariable logistic regression analysis with adjustment for age, sex, body mass index, and the prevalence of smoking revealed that the 1648A→G polymorphism of the integrin, alpha-2, gene (ITGA2; odds ratio 1.38) was significantly (P < 0.01) associated with hypertension, with the 1648G allele representing a risk factor for this condition. Furthermore, the −30G→A polymorphism of the glucokinase gene (GCK; odds ratio 0.84), the A→G polymorphism of the hypertension-associated SA, rat, homolog of, gene (SAH; odds ratio 0.69), the 1117C→A polymorphism of the prostaglandin I2 synthase gene (PTGIS; odds ratio 0.85) were significantly (P < 0.01) associated with hypertension, with variant alleles being protective against this condition. A stepwise forward selection procedure demonstrated that ITGA2, GCK, and PTGIS genotypes significantly and independently affected the prevalence of hypertension. Combined genotype analysis of three polymorphisms (ITGA2, GCK , and PTGIS) yielded a lowest odds ratio of 0.47 for the genotypes of AA or AG for ITGA2, GA or AA for GCK, and CC for PTGIS.
Conclusion Genetic variant of ITGA2 may be a risk factor for hypertension, whereas variants of GCK and PTGIS may be protective against this condition. Determination of genotypes and the combined genotypes for these genes may prove informative for assessment of genetic risk for hypertension and may contribute to personalized prevention of this condition.