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Although various loci and genes have been implicated in predisposition to hypertension by genetic linkage analyses and candidate gene association studies, the genes that confer susceptibility to this condition remain to be identified definitively. We have now examined the relationships of 22 candidate gene polymorphisms with the prevalence of hypertension and with blood pressure (BP) in a 6-year population-based longitudinal cohort study and observed significant relationships of three polymorphisms of SORBS1, GCK and WISP1 with hypertension. The 2233 subjects (1106 women, 1127 men) were aged 40-79 years and were randomly recruited to a population-based prospective cohort study of aging and age-related diseases in Japan. BP was measured with subjects having rested in the sitting position for at least 15 min. Genotypes for the 682A --&gt; G (Thr228Ala) polymorphism of SORBS1, the -30G --&gt; A polymorphism of GCK and the 2364A --&gt; G polymorphism of WISP1 were determined by melting curve analysis. Longitudinal analysis with a generalized estimating equation revealed that the polymorphisms of SORBS1 and GCK and that of WISP1 were significantly associated with the prevalence of hypertension in women and men, respectively. Longitudinal analysis with a mixed-effect model revealed that the polymorphism of SORBS1 was significantly related to diastolic BP in women and that those of GCK and WISP1 were significantly related to both systolic and diastolic BP in women and men, respectively. These results suggest that SORBS1 and GCK are susceptibility loci for hypertension in Japanese women and that WISP1 is such a locus in men.

Association of polymorphisms of SORBS1, GCK and WISP1 with hypertension in community-dwelling Japanese individuals