Association Between The Gly972Arg Polymorphism In Insulin ReceptorSubstrate-1 (IRS-1) Gene And Type 2 Diabetes (T2DM) Mellitus In Type 2 Diabetic Pedigrees From Chinese Han People In Chengdu Area

OBJECTIVE: To investigate the association between the Gly972Arg polymorphism in insulin receptor substrate-1 (IRS-1) gene and type 2 diabetes (T2DM) mellitus in pedigrees of T2DM from Chinese Han Nationality in Chengdu Area.RESEARCH DESIGN AND METHODS: 43 pedigrees of T2DM (n=296) and 102 normal control subjects were recruited from Chinese Han nationality in Chengdu area. The case subjects ( pedigrees of T2DM ) consisted of 126 men and 170 women (mean age 43.28±18.49 years), including 109 patients with T2DM, 40 patients with impaired glucose regulation (IGR) and 147 individuals with normal glucose tolerant (NGT). The control subjects, who were recruited from unrelated healthy volunteers without family history of diabetes mellitus and had no history of diabetes mellitus, hypertention, and other endocrine diseases, were composed of 44 men and 58 women (mean age 44.57 ± 13.54 years). In these subjects, information of clinical characteristics ( such as BMI, WHR, fasting plasma glucose, blood pressure, TG, Ch ) was collected, meanwhile the insulin sensitivity and insulin secretion were assessed by oral glucose tolerance test ( OGTT ) and insulinreleasing test. The genotypes of case and control subjects were analyzed by an allele-specific assay using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP ).RESULTS: The genotype distribution of Gly972Arg polymorphism in insulin receptor substrate-1 (TRS-1) was in Hardy-Weinberg equilibrium (% =0.08, p =0.78 ). The data showed that the frequency of the Gly/Arg genotype was not different between case subjects ( 3.04% , 9/296 ) and control subjects (1.96%, 2/102 )(P = 0.82 ). Among the variants of case subjects, there were 2 patients with T2DM ( 1.83%, 2/109 ) , 4 patients with IGR ( 10%, 4/40 ) and 3 individuals with NGT ( 2.04%, 3/147 ). Logistic regression analysis adjusted by BMI, sex and age indicated that the Gly972Arg polymorphism in IRS-1 was not associated with T2DM (OR = 0.385, 95%CI 0.106 to 1.394, P = 0.146) . The results also showed that the subjects with the Gly972Arg mutation in IRS-1 compared with non-carriers have higher fasting plasma insulin level ( 20.73±6.18 vs. 17.32±9.74 in T2DM pedigree group; 18.35±13.79 vs. 12.22±4.95 in normal control group) and lower insulin sensitivity (Homa-IR: 5.81±1.95 vs. 5.25±5.21 in case subjects; 4.38±3.70 vs. 2.64±1.21 in normal control subjects). Logistic regression analysis adjusted by sex and age indicated that the Gly972Arg polymorphism in IRS-1 was not associated with obesity (OR=0.59, 95%CI 0.145-2.351, P =0.448). CONCLUSIONS: These results suggest that the Gly972Arg polymorphism in IRS-1 may be not related to type 2 diabetes mellitus in Chinese people.