ASP905TYR POLYMORPHISM OF PROTEIN PHOSPHATASE-1-G SUBUNIT GENE IN HYPERTENSION

A possible pathogenic polymorphism in the gene for the G subunit of th e glycogen-associated regulatory form of protein phosphatase 1 (PP1 G subunit), causing an Asp-to-Tyr substitution at codon 905 (Asp905Tyr), has been reported to be associated with insulin resistance and hypers ecretion of insulin in the white population. Since marked heterogeneit y has been reported in the association of mutations of candidate genes with essential hypertension between Japanese and other ethnic groups, we investigated the association of Asp905Tyr with essential hypertens ion in Japanese subjects. The frequency of the Tyr allele in Japanese control subjects (0.70) was much higher than that in the Danish popula tion (0.10, P<1x10(-8)), indicating that the Tyr allele, previously re ported as a rare variant in whits subjects, is a common allele in our population. The genotype distribution in Japanese hypertensive patient s(n = 109: Asp/Asp = 0.09, Asp/Tyr = 0.09, Tyr/Tyr = 0.52) was not sig nificantly different (chi(2) = 0.7, df=2, P>.6) from that in normotens ive control subjects (n=148; Asp/Asp=0.12, Asp/Tyr=0.36, Tyr/Tyr=0.52) . Among subjects with different PP1 G subunit genotypes, there was no difference in blood pressure, serum cholesterol, plasma glucose and in sulin levels, and glucose disposal rate estimated by the euglycemic hy perinsulinemic clamp test. These data indicate that the Asp905Tyr poly morphism of the PP1 G subunit is not associated with essential hyperte nsion, nor with insulin resistance and/or hyperinsulinemia in Japanese patients with essential hypertension, suggesting that the polymorphis m plays little if any role in susceptibility to insulin resistance or hypertension.