The aim of the present study is to investigate whether Met416Val (M416V) polymorphism of glycogen synthase (GYS1) gene is associated with insulin resistance in type 2 diabetes. In 100 type 2 diabetic subjects (66 men and 34 women), the M416V polymorphism of GYS1 gene was analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) as previously reported, and insulin resistance was assessed by euglycemic hyperinsulinemic clamp represented as M/I value, the mean of glucose infusion rate (M value) adjusted by steady state plasma insulin level. The means of age and body mass index (BMI) of the subjects were 53.1 +/- 11.6 (SD) years and 23.3 +/- 3.5 kg/m(2). The allele frequencies of M416V polymorphism were 82.0% for MM, 16.0% for MV, and 2.0% for VV, and subjects were subsequently divided into V(+) group (n = 18) and V(-) group In = 82) according to the presence or absence of V allele. There were no significant differences in age, BMI, blood pressure, fasting plasma glucose or insulin levels or glycosylated hemoglobin (HbA(1c)) levels between the V(+) and V(-) groups. No significant differences in either M or M/I value were found between the V(+) and V(-) groups (M value, 5.06 +/- 2.20 v 5.12 +/- 2.04 mg (.) kg(-1) (.) min(-1), P =.841; M/I value, 5.24 +/- 3.07 v 5.39 +/- 2.87 mg (.) kg(-1) (.) min(-1) mU(-1) (.) L, P =.576). BMI showed the strongest independent contribution to M/I value, but the presence of V allele did not in multiple regression analysis. In conclusion, the M416V polymorphism of GYS1 gene is not associated with insulin resistance in type 2 diabetes. (C) 2003 Elsevier Inc. All rights reserved.