Single nucleotide polymorphisms in the proximal promoter region of apolipoprotein M gene (apoM) confer the susceptibility to development of type 2 diabetes in Han Chinese
Single nucleotide polymorphisms in the proximal promoter region of apolipoprotein M gene (apoM) confer the susceptibility to development of type 2 diabetes in Han Chinese
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DOI：
10.1002/dmrr.641
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发表时间：
2007-01-01
影响因子：
8
通讯作者：
Liu, Ying
中科院分区：
文献类型：
--
作者：
Niu, Nifang;Zhu, Xilin;Liu, Ying
目的与胰岛素抵抗相关的血脂异常是2型糖尿病（T2 D）的重要特征之一。最近的研究表明，载脂蛋白M（apoM）是重要的前β-高密度β-脂蛋白（HDL）和胆固醇（CHO）的形成在巨噬细胞的HDL流出。方法采用单核苷酸多态性（SNPs）分析方法，对中国汉族人群apoM基因近端启动子区C-1065 A、T-855 C和T-778 C多态性进行分析，探讨apoM基因多态性与2型糖尿病的关系。采用聚合酶链反应-限制性片段长度多态性技术对170例2型糖尿病患者和156例非糖尿病对照者进行基因分型结果T2 D患者T-778 C单标记分析显示，与非糖尿病对照组相比，T2 D患者C等位基因频率增加（10.6%vs5.8%，P = 0.026，OR = 1.934）。在非糖尿病对照组中，CT和CC基因型携带者的血浆CHO（221.7 vs 204.2 mg/dL，P = 0.033）和空腹血糖（FPG）（92.6 vs 89.7 mg/dL，P = 0.041）水平高于TT基因型受试者。校正年龄、BMI、SBP、DBP、CHO和TG的进一步分析表明，该SNP与T2 D强烈相关（P = 0.013，OR = 2.287）。然而，对这三个SNP的单倍型分析，结论apoM基因近端启动子区T-778 C单核苷酸多态性与血浆CHO和FPG水平相关，并可能是T2 D的危险因素。在汉族人中。版权所有（c）2006约翰威利父子有限公司。
Objective Dyslipidemia correlating to insulin resistance is one of the key features in type 2 diabetes (T2D). Recent studies have demonstrated that apolipoprotein M (apoM) is important for the formation of pre beta-high-density p lipoprotein (HDL) and cholesterol (CHO) efflux in macrophages to HDL. In the present study, we investigated the potential association of apoM genetic variation with the development of T2D.Methods Single nucleotide polymorphisms (SNPs) C-1065A, T-855C and T-778C in the proximal promoter region of apoM gene were validated to represent in Han Chinese. Further genotyping experiments in 170 T2D patients and 156 non-diabetic control subjects were performed with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).Results Single marker analysis for SNP T-778C indicated that T2D) patients had increased frequency of C allele in comparison with non-diabetic controls (10.6% versus 5.8%, P = 0.026, OR = 1.934). In non-diabetic controls the, carriers with CT and CC genotypes had higher plasma CHO (221.7 versus 204.2 mg/dL, P = 0.033) and fasting plasma glucose (FPG) (92.6 versus 89.7 mg/dL, P = 0.041) levels than the subjects with TT genotype. Further analysis with adjustment for age, BMI, SBP, DBP, CHO and TG demonstrated that this SNP was strongly associated with T2D) (P = 0.013, OR = 2.287). Haplotype analysis for those three SNPs, however, indicated that the common haplotypes were less informative than studying the role of the T-778C variant independently of the haplotype context.Conclusion The present study provided the first evidence that SNP T-778C in the proximal promoter region of apoM gene was associated with the levels of plasma CHO and FPG and also conferred the risk in the development of T2D) among Han Chinese. Copyright (c) 2006 John Wiley & Sons, Ltd.