2型糖尿病家系脂联素基因多态性研究
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国家自然科学基金(30270632).


Polymorphism of adiponectin gene in pedigree of type 2 diabetes mellitus
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    摘要:

    目的:研究脂联素(adiponectin)APMl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:应用聚合酶链反应一限制性内切酶片段长度多态性技术,选择3个APMl基因SPNs位点:一11377C〉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)对一11377C〉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。

    Abstract:

    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.

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