载脂蛋白M基因启动子区域的单核苷酸多态性C-724/del与2型糖尿病相关。

A single-nucleotide polymorphism C-724 /del in the proter region of the apolipoprotein M gene is associated with type 2 diabetes mellitus.

作者信息

Zhang Pu-Hong, Gao Jia-Lin, Pu Chun, Feng Gang, Wang Li-Zhuo, Huang Li-Zhu, Zhang Yao

机构信息

Anhui Province Key Laboratory of Biological Macro-molecules Research, Wannan Medical College, Wuhu, People's Republic of China.

Department of Endocrinology and Genetic Metabolism, Yijishan Hospital of Wannan Medical College, Wuhu, People's Republic of China.

出版信息

Lipids Health Dis. 2016 Aug 30;15(1):142. doi: 10.1186/s12944-016-0307-3.

DOI:10.1186/s12944-016-0307-3

PMID:27576735

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5006532/

Abstract

BACKGROUND

Apolipoprotein M (apoM) was the carrier of the biologically active lipid mediator sphingosine-1-phospate in high density lipoprotein cholesterol (HDL-C) and played a critical role in formation and maturation of prebeta-HDL-C particles. The plasma apoM levels were decreased obviously in patients with type 2 diabetes mellitus (T2DM). A new single-nucleotide polymorphism (SNP) C-724del in apoM promoter was associated with a higher risk for coronary artery diseases (CAD) and myocardial infarction, could reduce promoter activities and apoM expression in vitro. The primary aim of the present case-controls study was to investigate the effect of apoM SNP C-724del on apoM expression in vivo and its association with T2DM susceptibility in an eastern Han Chinese cohort.

METHODS

Two hundred and fifty-nine T2DM patients and seventy-six healthy controls were included in this study. Amplifying DNA of apoM proximal promoter region including SNP C-724del by Real-Time Polymerase Chain Reaction (RT-PCR) and amplicons sequencing. The plasma apoM concentrations were assayed by enzyme linked immunosorbentassay (ELISA).

RESULTS

Four polymorphic sites, rs805297 (C-1065A), rs9404941 (T-855C), rs805296 (T-778C), C-724del were confirmed. rs805297 (C-1065A) and rs9404941 (T-855C) showed no statistical difference in allele frequencies and genotype distributions between T2DM patients and healthy controls just as previous studies. It's worth noting that the difference of rs805296 (T-778C) between these two groups was not found in this study. In SNP C-724del, the frequency of del allele and mutant genotypes (del/del, C/del) were higher in T2DM patients compared with healthy controls (p = 0.035; P = 0.040, respectively), while the plasma apoM levels of C-724del mutant allele carriers compared with the wide-type homozygotes carriers were not statistically different in T2DM patients (18.20 ± 8.53 ng/uL vs 20.44 ± 10.21 ng/uL, P = 0.245).

CONCLUSION

The polymorphism C-724del in the promoter region of the apoM gene could confer the risk of T2DM among eastern Han Chinese. Unfortunately, the lowing of plasma apoM levels of C-724del mutant allele carriers compared with the wide-type homozygotes carriers in T2DM patients was not statistically different in present study, so further researchs were needed by enlarging the sample.

摘要

背景

载脂蛋白M（apoM）是高密度脂蛋白胆固醇（HDL-C）中生物活性脂质介质鞘氨醇-1-磷酸的载体，在前β-HDL-C颗粒的形成和成熟中起关键作用。2型糖尿病（T2DM）患者的血浆apoM水平明显降低。apoM启动子中的一种新的单核苷酸多态性（SNP）C-724del与冠状动脉疾病（CAD）和心肌梗死的较高风险相关，在体外可降低启动子活性和apoM表达。本病例对照研究的主要目的是在一个东汉中国人群队列中研究apoM SNP C-724del对体内apoM表达的影响及其与T2DM易感性的关系。

方法

本研究纳入了259例T2DM患者和76例健康对照。通过实时聚合酶链反应（RT-PCR）扩增包括SNP C-724del的apoM近端启动子区域的DNA并进行扩增子测序。采用酶联免疫吸附测定（ELISA）法检测血浆apoM浓度。

结果

确认了4个多态性位点，即rs805297（C-1065A）、rs9404941（T-855C）、rs805296（T-778C）、C-724del。rs805297（C-1065A）和rs9404941（T-855C）在T2DM患者和健康对照之间的等位基因频率和基因型分布无统计学差异，正如先前的研究。值得注意的是，本研究未发现这两组之间rs805296（T-778C）的差异。在SNP C-724del中，T2DM患者中缺失等位基因和突变基因型（del/del、C/del）的频率高于健康对照（分别为p = 0.035；P = 0.040），而在T2DM患者中，C-724del突变等位基因携带者与野生型纯合子携带者的血浆apoM水平无统计学差异（18.20±8.53 ng/uL对20.44±10.21 ng/uL，P = 0.245）。