Motoyama Koka, Emoto Masanori, Tahara Hideki, Komatsu Miyoko, Shoji Tetsuo, Inaba Masaaki, Nishizawa Yoshiki
Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Japan.
Metabolism. 2003 Jul;52(7):895-9. doi: 10.1016/s0026-0495(03)00075-1.
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/m2. 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 (n=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 (HbA1c) 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 x kg(-1) x min(-1), P=.841; M/I value, 5.24+/-3.07 v 5.39+/-2.87 mg x kg(-1) x min(-1) x mU(-1) x 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.
本研究旨在探讨糖原合酶（GYS1）基因的Met416Val（M416V）多态性是否与2型糖尿病患者的胰岛素抵抗相关。按照先前报道的方法，采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）分析法，对100例2型糖尿病患者（66例男性和34例女性）的GYS1基因M416V多态性进行分析；通过正常血糖高胰岛素钳夹技术评估胰岛素抵抗，以M/I值表示，即根据稳态血浆胰岛素水平调整后的葡萄糖输注率（M值）的平均值。研究对象的年龄和体重指数（BMI）平均值分别为53.1±11.6（标准差）岁和23.3±3.5kg/m²。M416V多态性的等位基因频率分别为：MM为82.0%，MV为16.0%，VV为2.0%；随后根据是否存在V等位基因，将研究对象分为V（+）组（n = 18）和V（-）组（n = 82）。V（+）组和V（-）组在年龄、BMI、血压、空腹血糖或胰岛素水平以及糖化血红蛋白（HbA1c）水平方面均无显著差异。V（+）组和V（-）组之间的M值或M/I值均无显著差异（M值：5.06±2.20对5.12±2.04mg·kg⁻¹·min⁻¹，P = 0.841；M/I值：5.24±3.07对5.39±2.87mg·kg⁻¹·min⁻¹·mU⁻¹·L，P = 0.576）。BMI对M/I值的独立贡献最大，但在多元回归分析中，V等位基因的存在并无此作用。总之，GYS1基因的M416V多态性与2型糖尿病患者的胰岛素抵抗无关。
