【作者】 王桂凤；

【导师】 张东峰；

【作者基本信息】 青岛大学 ， 临床检验诊断学， 2011， 硕士

【摘要】 目的探讨KCNJ11基因与青岛地区汉族人群2型糖尿病和肥胖的相关性以及WFS1基因单核苷酸多态性与2型糖尿病的关系。方法运用病例-对照研究,采用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)技术,对青岛地区188例2型糖尿病病人和170例对照者的KCNJ11基因E23K和rs2285676位点多态性进行基因型分析,并对160例肥胖和117例对照者的KCNJ11基因E23K位点多态性进行基因型分析；应用PCR-RFLP技术分析209例2型糖尿病病人和211例对照者的WFS1基因R456H位点的多态性。结果T2DM组KCNJ11基因E23K位点EE、EK、KK3种基因型频率分别是38.8%、44.7%和16.5%,对照组分别为34.1%、51.8%和14.1%；两组基因型频率分布比较,差异无显著性(x2=1.801,P>0.05)；K等位基因频率在病例组和对照组中分别为38.8%和40%,两组比较差异亦无显著性(x2=0.102,P>0.05)。T2DM组KCNJ11基因rs2285676位点CC、CT、TT3种基因型频率分别是22.3%、54.3%和23.4%,对照组分别为21.8%、48.2%和30%；T2DM组与对照组基因型频率分布比较,差异无显著性(x2=2.106,P>0.05)；T2DM组和对照组T等位基因频率分别为50.5%和54.1%,两组等位基因频率比较,差异无显著性(x2=0.920,P>0.05)。调整性别、年龄、WHR、BMI、TC和血压等因素,Logistic回归分析未发现KCNJ11基因与青岛地区汉族人2型糖尿病相关。单因素非条件Logistic回归分析结果显示,与EE基因型比较,EK和KK基因型与肥胖均无相关性。调整年龄、性别、血糖和血脂等因素进行多因素非条件Logistic回归分析表明,与EE基因型比较,EK基因型与肥胖无关联,而KK基因型与肥胖存在相关性(OR=2.843,P<0.05)。T2DM组WFS1基因多态性R456H位点GG、GA、AA3种基因型频率分别是74.6%、20.1%和5.3%,对照组分别为82%、15.2%和2.8%,两组基因型频率分布比较,差异无显著性(x2=3.691,P>0.05)；T2DM组G、A等位基因频率分别为84.7%和15.3%,对照组分别为89.6%和10.4%,两组G、A等位基因频率比较,差异有显著性(x2=4.472,P<0.05)。无论经单因素还是多因素非条件Logistic回归分析,均未发现R456H位点基因型与青岛地区汉族人2型糖尿病相关,而A等位基因与2型糖尿病具有相关性(OR=1.564,P<0.05)。结论KCNJ11基因E23K位点KK基因型可能是青岛地区汉族人肥胖的危险因素。WFS1基因R456H位点A等位基因可能是青岛地区汉族人2型糖尿病的遗传危险因子。更多还原

【Abstract】 Objective To explore the correlation of KCNJ11 gene polymorphisms with type 2 diabetes mellitus and obesity and to analyze the relationship between WFS1 gene polymorphism and type 2 diabetes mellitus in Han ethnic population in Qingdao area.Methods Case-control designs was used and two single nucleotide polymorphisms (SNPs) E23K and rs2285676 in the KCNJ11 gene were genotyped in 188 type 2 diabetic patients and 170 control subjects and the E23K polymorphism in the KCNJ11 gene were genotyped in 160 obesity patients and 170 control subjects by a polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP); the WFS1 gene R456H polymorphism was analyzed using PCR-RFLP in 209 type 2 diabetic patients and 211 control subjects.Results The frequencies of EE, EK and KK genotype were 38.8%,44.7% and 16.5%, respectively, in T2DM group, and 34.1%,51.8% and 14.1%, respectively, in control group. Frequency of KK genotype in T2DM group was higher than that for controls. The frequencies of K allele were 38.8% and 40% in T2DM group and control group, respectively. No significant difference in the distribution rate of genotype was found between T2DM group and control group (χ2=1.801, P>0.05), and no significant difference in the allelic frequencies existed between the two groups(χ2=0.102,P>0.05). The frequencies of CC, CT and TT genotype were 22.3%,54.3% and 23.4%, respectively, in T2DM group, and 21.8%,48.2% and 30%, respectively, in control group. The frequencies of T allele were 50.5% and 54.1% in T2DM group and control group, respectively. No significant differences in the distribution rate of genotype and allelic frequencies existed between the two groups (χ2= 2.106, P>0.05 vsχ2=0.920, P>0.05). After adjusting sex, age, WHR, BMI, TC and hypertension, multiple factors, unconditional Logistic regression analysis showed there was no relationship between type 2 diabetes and KCNJ11 gene.After single factors unconditional Logistic regression analysis, no association was found between obesity and EK and KK genotype, compaired with EE genotype respectively. Compaired with EE genotype, EK genotype was not associated with obesity, but KK genotype was associated with obesity, after multiple factors unconditional Logistic regression analysis (OR=2.843, P<0.05) The frequencies of GG, GA and AA genotype were 74.6%,20.1%and 5.3%, respectively, in T2DM group, and 82%,15.2% and 2.8%, respectively, in control group. Frequency of AA genotype in T2DM group was higher than that for controls. But there was no significant difference in the distribution rate of genotype between T2DM group and control group (χ2= 3.691, P>0.05). The frequencies of A allele were 15.3% and 10.4% in T2DM group and control group, respectively. The allelic frequencies showed significant difference between the two groups (χ2=4.472, P<0.05). Logistic regression analysis indicated that the WFS1 R456H genotype was not associated with type 2 diabetes. But there was a relationship between A allele and type 2 diabetes (OR= 1.564, P<0.05)Conclusion The KK genotype of E23K in KCNJ11 is a risk factor of obesity in Han ethnic population in Qingdao area. The A allele of WFS1 R456H serves as a genetic risk factor of T2DM in Han ethnic population in Qingdao area.更多还原