2型糖尿病家系脂联素基因多态性研究  

Polymorphism of adiponectin gene in pedigree of type 2 diabetes mellitus

作　　者：王吉影[1] 王艳波[2] 于永春[2] 李智[2] 滕小洪[2] 王红玲[2] 

机构地区：[1]同济大学附属第十人民医院内分泌科,上海200072 [2]同济大学附属第十人民医院中心实验室

出　　处：《第二军医大学学报》2007年第2期143-147,共5页Academic Journal of Second Military Medical University

基　　金：国家自然科学基金(30270632).~~

摘　　要：目的研究脂联素(adiponectin)APM1基因单核苷酸多态性(single nucleotide polymorphism,SNP)与2型糖尿病的关联性。方法应用聚合酶链反应-限制性内切酶片段长度多态性技术,选择3个APM1基因SPNs位点-11377C>G、+45T>G和+276G>T,对75个2型糖尿病家系(337例)进行基因分型,并以Genehunter软件分析单个SNP在家系中传递不平衡(transmission-disequilibrium,TDT)情况和多个SNPs所构成的单倍型传递情况,同时进行人体测量学、血糖、血脂等临床参数的检测。结果(1)经TDT分析,未发现APM1基因SNPs单个位点在2型糖尿病患病子代中优势传递;(2)所检测的3个SNPs所构成的单倍型在患病子代中未见优势传递;(3)对-11377C>G位点不同基因型生理、生化指标分析在糖代谢异常组,GG基因型体质量指数(BMI)、腰围(WC)明显高于CC基因型(P=0.032,P=0.030);G等位基因携带者HDL-C水平低于CC基因型(P=0.006),而空腹胰岛素(FINS)水平高于CC基因型(P=0.011);在家系正常对照组,G等位基因携带者FINS水平明显低于CC基因型(P=0.021);(4)对+45T>G多态性的分析在糖代谢异常组,GG基因型BMI明显高于TT基因型(P=0.036),而FINS水平明显低于TT基因型(P=0.014);(5)对+276G>T多态性的研究在家系正常组,T等位基因携带者的BMI明显低于GG基因型(P=0.043)。结论未发现APM1基因3个多态性位点与2型糖尿病存在相关性。但APM1基因对胰岛B细胞功能、肥胖可能有一定影响。Objective： To investigate the correlation between the single nucleotide polymorphism （SNP） of adiponectin （APM1） gene and type 2 diabetes mellitus. Methods： Three common binding sites （-11377C〉G, ＋45T〉G, and ＋276G〉 T） of SNP on the APM1 gene were genotyped by polymerase chain reaction-restriction fragment length polymorphism （PCRRFLP） assay in 75 pedigrees （337 individuals） of type 2 diabetes mellitus. Genehunt software was used to analyze the transmission-disequilibrium （TDT） and to calculate SNP combining haplotypes. Meanwhile, the physiological and biochemical parameters were also determined in the pedigrees of type 2 diabetes mellitus. Results： We found no preferential transmission in the tested binding sites or any haplotypes of SNP in the APM1 gene in the filial generation of type 2 diabetes mellitus. In type 2 diabetes mellitus group, GG genotype had higher body mass index （BMI）（P=0. 032） and waist circumference （WC）（P= 0. 030） compared to CC genotype in the patients with SNP-11377 binding site; patients with G allele had lower levels of highdensity lipoprotein cholesterol （HDL-C）（P= 0. 006）and higher levels of fasting plasma insulin （FINS） （P= 0. 011） as compared to CC genotype. However, FINS levels （P=0. 021） in subjects with CC genotype were significantly lower than those with G allele in healthy control group. For patients with SNP＋45 binding site, those with GG genotypes had higher BMI （P=0. 036） and lower levels of FINS （P=0. 014） than those with TT genotypes in both groups. For patients with SNP＋276 binding site, those with GG genotypes had higher BMI（P=0. 043） than those with T allele in the control group. Conclusion： The SNP of the APM1 gene is not associated with the pedigrees of type 2 diabetes mellitus, but APM1 gene has influence on the function of insulin B cells and the development of obesity.

关 键 词：脂联素基因 多态性 单核苷酸 糖尿病 2型 

分 类 号：R587.1[医药卫生—内分泌]