摘要
目的将维生素D受体基因作为糖尿病肾病候选基因,探讨维生素D受体基因FokⅠ酶切位点多态性与中国汉族人群糖尿病肾病之间的关系。方法①选择2003-06/2004-08在南京医科大学第二附属医院内分泌科及常州市第二人民医院内分泌科住院2型糖尿病患者94例为糖尿病组,男30例,女64例。②根据3次晨尿尿白蛋白与肌肝比值将2型糖尿病患者分为3组尿白蛋白与肌肝比值<30m g/g为正常白蛋白尿组(n=55),30m g/g≤尿白蛋白与肌肝比值<300m g/g者为微量白蛋白尿组(n=32),尿白蛋白与肌肝比值≥300m g/g为大量白蛋白尿组(n=7)。微量白蛋白尿组和大量白蛋白尿组合称为异常白蛋白尿组。病程≥5年未合并糖尿病肾病31例为迟发/未发糖尿病肾病组,病程≤1年伴有肾病患者20例为早发糖尿病肾病组。选择同期本院健康体检者77人为对照组,男35人,女42人。纳入对象均为汉族人,均对实验目的知情同意。③采用多聚酶链反应-限制性片段长度多态性方法检测维生素D受体基因多态性等位基因频率和基因型频率。④对数据先进行正态分布检验,若符合正态分布,两组间计量资料均数的比较,用t检验,多组间比较用F检验。计算维生素D受体基因多态性的基因型频率,确认符合H ardy-W einberg平衡,计算等位基因频率。等位基因频率和基因型频率分布比较采用χ2检验。基因型分布作H ardy-W einberg吻合度检验。相对风险率(RR)表示疾病与标志性状关联的强度。结果健康者77例和2型糖尿病患者94例均进入结果分析。①中国汉族人群维生素D受体基因FokⅠ酶切位点有2种等位基因F,f;存在3种基因型FF,Ff,ff。②对照组、正常白蛋白尿组、微量白蛋白尿组和大量白蛋白尿组间维生素D受体基因型频率分布具有显著性差异(χ2=21.137,P=0.002);等位基因频率分布差异具有显著性(χ2=366.924,P<0.001)。③正常白蛋白尿组和异常白蛋白尿组维生素D受体基因型频率分布差异有显著性(χ2=12.131,P=0.002),等位基因频率分布差异也有显著性(χ2=13.884,P=0.000)。④等位基因f与异常白蛋白尿的发生相关联(RR=3.57,P<0.005),具有显著性意义,表明具有等位基因f的2型糖尿病患者发生糖尿病肾病的可能性是没有等位基因f的糖尿病患者的3.57倍。等位基因F与异常白蛋白尿的发生呈负关联(RR=0.21,P<0.005)。结论维生素D受体基因多态性与糖尿病肾病易感性相关联,等位基因f是糖尿病肾病的易感基因,是早发糖尿病肾病的危险因素。
AIM： To take vitamin D receptor gene as the candidate gene for diabetic nephropathy, and investigate the correlation between vitamin D receptor gene Fok I restriction site polymorphism and the diabetic nephropathy within a Chinese population. METHODS： （1） Between June 2003 and August 2004, 94 inpatients （30 males and 64 females） with type 2 diabetes mellitus （diabetic group） were selected from the Department of Endocrinology of the Second Affiliated Hospital of Nanjing Medical University and that of Changzhou Second People＇s Hospital. （2） According to the ratio of morning urine albumin to ereatinine for 3 times, the type 2 diabetic patients were divided into 3 groups： normal alhuminuria group （n=55, ratio 〈 30 mg/g）, trace albuminuria goup （n=32, 30 mg/g ≤ ratio 〈 300 mg/g） and mass albuminuria group （n=7, ratio ≥ 300 mg/g）, and the latter two groups were taken as abnormal albuminuria group. 31 cases with disease course ≥ 5 years without diabetic nephropathy were taken as the delayed/none diabetic nephropathy group, and 20 cases with disease course ≤5 years accompanied by diabetic nephropathy were taken as the early diabetic nephropathy group. Meanwhile 77 healthy physical examinees （35 males and 42 females） in the same hospitals were taken as the control group. All the subjects were Han people, and participated in the study voluntarily. （3） The allele frequency and genotypie frequency of vitamin D receptor gene polymorphism were detected with polymerase chain reaction-restriction fragment length polymorphism analysis. （4） The data were firstly treated with normal distribution test. If accorded with the normal distribution, the mean of the measurement data between two groups were compared with the t test, and the F test was applied in the comparison among many groups. The genotypic frequency of vitamin D receptor gene polymorphism was calculated, and identified to he accorded with Hardy-Weinberg balance, and then the allele frequency was also calculated. The distribution of genotypie frequency and allele frequency were compared with the ehi- square test. The Hardy-Weinberg test of goodness of fit was applied to the genotypie distribution. The relative risk （RR） manifested the intensity of correlation between disease and mark character. RESULTS： All the 77 healthy subjects and 94 type 2 diabetic patients were involved in the analysis of results. （1） At the vitamin D receptor gene Fok I restriction site polymorphism in Chinese Han population, there were 2 alleles of F and f, and 3 genotypes of FF, Ff and ft. （2） The distribution of vitamin D receptor genotypie frequency was significantly different among the control group, normal albuminuria group, trace albuminuria group and mass albuminuria group （X^2=21.137, P=0.002）, and the distribution of allele frequency was also significantly different （X^2=366.924, P 〈 0.001）. （3） The distribution of vitamin D receptor genotypie frequency was significantly different between normal albuminuria group and abnormal albuminuria group （X^2=12.131,P=0.002）, and the distribution of allele frequency was also significantly different （X^2=13.884, P=0.000）. （4） The f allele was significantly correlated with the occurrence of abnormal albuminuria （RR=3.57,P 〈 0.005）, indicating that the probability of occurring diabetic nephropathy in the type 2 diabetic patients with f allele was 3.57 times of that in those without f allele. The F allele was had negative correlation with the occurrence of abnormal albuminuria （RR=0.21, P 〈 0.005）. CONCLUSION： Vitamin D receptor gene is associated with the susceptibility of diabetic nephropathy, f allele is the predisposing gene of diabetic nephropathy, and it is the risk factor of early diabetic nephropathy.
出处
《中国临床康复》
CSCD
北大核心
2005年第47期1-4,共4页
Chinese Journal of Clinical Rehabilitation
基金
江苏省卫生厅基金项目(H200128)~~
