The Association Between INSIG1Gene Rs9769826and Rs9769506Polymorphisms And Type2Diabetes Mellitus

Objective To explore the relationship between rs9769826and rs9769506single nucleotide polymorphisms of INSIG1gene and type2diabetes in Han population of Qingdao, and to analyze the interactions between rs9769826mutation in INSIG1Gene and High total cholesterol(TC),waist-to-Hip Ratio (WHR), hypertension in type2diabetes mellitus.Methods Selecting125patients with type2diabetes and125normal controls by using frequency matched case-control study design. The rs9769826polymorphism of INSIG1gene was genotyped by using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.The differences of genotypic and allelic frequencies were compared between patients with type2diabetes and normal controls. Anthropometries and biochemical indicators were measured for all subjects, and calculated body mass index (BMI) and waist-hip ratio (WHR). Multiple factors unconditional Logistic regression was used to analyze the risk factors of type2diabetes mellitus.Additive model was used to analyze the interactions between rs9769826mutation in INSIG1gene and High total cholesterol(TC),waist-to-Hip Ratio (WHR) hypertension in type2diabetes mellitus.Results The frequencies of AA, AG and GG genotypes were58.4%,37.6%and4.0%, respctively, in case group, and76.8%,20.0%and3.2%, respctively, in control group. There were significant differences in genotypes frequencies between patients with type2diabetes and normal controls.(χ2=9.964, P<0.01), G allele frequency was22.8%in case group, significantly higher than that of13.2%in control group,(%=7.805, P<0.01).after adjusting age, gender, BMI, WHR, blood pressure and blood fats by logistic regression, AG+GG genotype of carrying mutation G was associated with T2DM (OR=3.220,95%CI=1.550-6.686)Two genetypes of rs9769506were detected, i.e., CC and AC, but no AA was detected. The frequencies of CC and AC genotypes were96.0%and4.0%,in case group,97.6%and2.4%, in control group, there were no significant differences in genotypes frequencies between patients with type2diabetes and normal controls(χ2=0.517,P>0.05); The frequencies of A allele were2.0%and1.2%in case group and control group, respectively. No significant difference in the allelic frequencies existed between the two groups (χ2=0.508,P>0.05). Logistic regression analysis indicated that the rs9769506mutation was not associated with type2diabetes (P>0.05)After adjusting age, gender, body mass index (BMI) and blood fats by logistic regression, the rs9769826mutation of INSIG1gene and high total cholesterol show a positive interaction, attributable interaction was3.346, attributable interaction percentage was30.96%, pure attributable interaction percentage was34.12%, synergy index was1.52. The rs9769826mutation of INSIG1gene and abnormality of WHR also show a positive interaction, the indexes mentioned above were2.901,45.17%,53.49%and2.125, respectively.The rs9769826mutation of INSIG1gene and hypertension also show a positive interaction, the indexes mentioned above were5.233,68.96%,79.43%and4.86, respectively.Conclusion1.The rs9769826polymorphism of INSIG1gene was associated with type2diabetes in Qingdao Han population, G allele was a genetic risk factor of T2DM.2. The rs9769506polymorphism of INSIG1gene was not associated with type2diabetes.3. The study indicated that risk factors of T2DM, i.e, High total cholesterol(TC), abnormality of Waist-to-Hip Ratio (WHR), hypertension and the rs9769826mutation of INSIG1gene were associated with increased risks of T2DM, and the rs9769826mutation of INSIG1gene was interacted with high total cholesterol(TC), abnormality of Waist-to-Hip Ratio (WHR) and hypertension. To control TC, abnormality of WHR and hypertension in the population who had rs9769826G allele of INSIG1gene could significantly reduce the danger of residents suffering from type2diabetes.