The Association Study Of Resistin Gene +299G/A Polymorphisms With Type 2 Diabetes Mellitus And Macroangiopathy

Objective: To investigate the correlation of resistin gene +299G/Apolymorphisms with type 2 diabetes mellitus and macroangiopathy in Han Chinese in the north. The independent risk factors of type 2 diabetes mellitus and its macroangiopathy are found by Logistic regression.Methods: According to WHO 1999 diabetic criteria, 198 type 2 diabeticinpatients were selected ,male 105 cases,female 93 cases,age 59.33±10.92 years, from the medical ward of Endocrine and health care in provincial hospital affiliated to Shandong university during April to December in 2006. They were divided into two groups: group A were 123 cases without macroangiopathy,male 68 cases, female 55 cases, age 55.2±9.3 years;group B were 75 cases with macroangiopathy ,male 37 cases,female 38 cases,age 60.8±6.7 years.The control group was composed of healthy check-up outpatients ,male 57 cases,female 41 cases,age 55.7±9.1 years,without diabetes mellitus, cornary heart disease, hypertension, brain vascular disease, family history of diabetes mellitus or hypertension. The genotypes of +299G/A variant in resistin gene were determined with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay.Meanwhile body mass index (BMI), waist-to-hip ratio(WHR), systolic blood pressure(SBP) and diastolic blood pressure(DBP) were measured by the same one appointed. Serum total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), fasting blood glucose (FPG) and fibrinogen (Fib) were measured using an autoanalyzer. Fasting insulin (FINS) were measured by radionimmunoassay (RIA).Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated as (FINS×FPG)/22.5. All statistical tests were carried out using the SPSS 11.5-program.The differences in genotype frequencies between the cases and controls were tested usingχ²-test.The associations in cases between genotype and clinical features were tested using T test. Measurement date interclass was indicated with x±s.Correlations of many factors were analysed by Logistic regression.Results:1. The colony has representative by Hardy-Weinberg equilibrium to all genotypes of +299G/A at resistin gene (χ² (A group) =3.07, P>0.50;χ² (B group) =2.71, P>0.05;χ² (control group) =0.004, P>0.05). Compared with the control group, the frequencies of genotype and allele were significantly different in group B, also having different allele frequency from group A (P=0.038, 0.016, 0.024).2. Both age and gender of the experiment group matched the control.The number of SBP, DBP, FPG, HOMA-IR, Fib, WHR, HbA₁c in diabetic group were significantly higher than those in the control group (P<0.05).3. Compared with type 2 diabetic patients without macroangiopathy, the diabetic patients with macroangiopathy had much higher levels of age (60.84±6.68 vs 55.19±9.26 years), SBP (149.15±21.83 vs 136.46±20.68 mmHg), HbA₁c(10.8±2.79 vs 9.85±2.37 %), HOMA-IR(5.35±3.47 vs 3.84±2.53) ,TC(5.43±1.25 vs 5.05±1.12 mmol/L), LDL-C(3.23±0.95 vs 2.85±0.65 mmol/L), Fib(3.83±1.03 vs 3.46±0.95 mmol/L ), WHR(0.97±0.007 vs 0.04±0.007), duration of diabetes (11.57±6.33 vs 8.49±5.53 years), duration of hypertension (8.39±10.06 vs 3.3±7.23 years)(P<0.05).4. In diabetic group, there was association between resistin gene +299G/A polymorphisms and clinical characteristics, including WHR and FPG.The subgroup of G/A genotype had much lower WHR than G/G one (P<0.05), but having higher FPG than A/A one (P<0.05).There was no association between genotypes and other clinical characteristics (P>0.05).5. In control group, people with GG genotype had higher FPG than those with G/A or A/A (P=0.001, P=0.006), but had higher BMI than those only with G/A (P=0.042). Stepwise regression analysis showed that BMI, LDL-C, Fib were independent risk factors for FPG.6. In group A, there was no association between resistin gene +299G/A polymorphisms and clinical characteristics, such as BMI, SBP, DBP, FPG, FINS, HbA₁c, TC, TG, HDL-C, Fib and so on(P>0.05).7. In group B, people with G/A genotype had higher FPG than those with A/A (P <0.05).Stepwise regression analysis showed that HbA₁c and TG were independent risk factors for FPG.8. Logistic regression showed that HOMA-IR, FINS and SBP were major risk factors for diabetes and the major risk factors for macroangiopathy were SBP, DBP, LDL-C and diabetic family history.Conclusion: Resistin gene +299G/A polymorphisms are associated withT2DM in Han Chinese of the north.People with A allele have lower FPG and BMI ,perhaps A allele is a tiny protective factor. People with A/A genotype have lower FPG in group B. Logistic regression shows that HOMA-IR, FINS and SBP are major risk factors for diabetes and the major risk factors for macroangiopathy are SBP, DBP, LDL-C and diabetic family history.