INSIG1基因rs9769826和rs9769506多态性与2型糖尿病的关联研究
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摘要
目的：探讨胰岛素诱导基因1(INSIG1) rs9769826和rs9769506单核苷酸多态性(SNPs)与青岛地区汉族人群2型糖尿病(T2DM)的关系以及INSIG1rs9769826多态性与高胆固醇、腰臀比异常和高血压之间的交互作用对2型糖尿病发病的影响。方法：采用频数匹配的病例对照研究方法,选取125名T2DM病人和125名正常对照者,应用聚合酶链式反应-限制性片段长度多态性检测技术(PCR-RFLP),对INSIG1基因rs9769826和rs9769506多态性进行基因分型,比较两组间基因型频率和等位基因频率；同时对所有研究对象进行人体测量学及生化指标检测,计算体质指数(BMI)和腰臀比(WHR)。应用多因素非条件Logistic回归分析INSIG1基因rs9769826和rs9769506多态性与T2DM的关系。应用相加模型分析INSIG1基因多态性与高胆固醇、腰臀比异常以及高血压之间的交互作用对T2DM发病的影响。结果：1. INSIG1基因rs9769826位点AA、AG、GG基因型频率在T2DM组中分别为58.4%、37.6%和4.0%,对照组分别为76.8%、20.0%和3.2%,两组比较差异具有显著性(x2=9.964,P<0.01)；两组间G等位基因频率分别为22.8%,13.2%,病例组高于对照组(x2=7.805,P<0.01)。多因素非条件Logistic回归调整年龄、性别、BMI、 WHR、血压、血脂等混杂因素后,分析结果显示,携带突变位点G的基因型(AG+GG)与T2DM仍有关联关系(OR=3.220,95%CI=1.550-6.686).2. INSIG1基因rs9769506位点未检测到AA基因型,T2DM组CC和AC基因型频率分别为96.0%和4.0%,在对照组中分别为97.6%和2.4%,两组比较差异无统计学意义(x2=0.517,P>0.05)；T2DM组和对照组A等位基因频率分别为2.0%和1.2%,两组比较差异无显著性(x2=0.508,P>0.05)。多因素非条件Logistic回归分析结果显示,该变异与T2DM无关联关系(P>0.05)。3.经调整年龄、性别、体重指数、血脂等混杂因素后,INSIG1基因rs9769826变异与高胆固醇存在正交互作用,归因交互效应[I(AB)]、归因比(AP%)、纯交互作用归因比(AP*%)、交互作用指数(S)分别为3.346、30.96%、34.12%和1.52。INSIG1基因rs9769826变异与腰臀比异常亦有在正交互作用,其I(AB)、AP%、AP*%、S分别为2.901、45.17%、53.49%和2.125。INSIG1基因rs9769826变异与高血压亦存在正交互作用,其I (AB)、AP%、AP*%、S分别为5.233、58.96%、79.43%和4.86。结论：1.INSIGI基因rs9769826位点多态性与青岛地区汉族人群T2DM有关联关系,G等位基因是T2DM遗传风险因子。2.INSIG1基因rs9769506位点多态性与T2DM无关联关系。3.T2DM的发生是环境与遗传因子综合作用的结果,INSIG1基因rs9769826变异与高胆固醇、腰臀比异常以及高血压在T2DM发生中具有一定的交互作用。在携带INSIG1基因rs9769826G等位基因的人群中,控制胆固醇、腰臀比以及血压可明显降低居民患T2DM的危险。
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.
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.
引文
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