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MCF2L2、ADIPOQ 和 SOX2 基因多态性对 1 型糖尿病肾病发生的影响。

Effects of MCF2L2, ADIPOQ and SOX2 genetic polymorphisms on the development of nephropathy in type 1 Diabetes Mellitus.

机构信息

Rolf Luft Center for Diabetes Research, Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Solna, Stockholm, Sweden.

出版信息

BMC Med Genet. 2010 Jul 28;11:116. doi: 10.1186/1471-2350-11-116.

DOI:10.1186/1471-2350-11-116
PMID:20667095
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2919463/
Abstract

BACKGROUND: MCF2L2, ADIPOQ and SOX2 genes are located in chromosome 3q26-27, which is linked to diabetic nephropathy (DN). ADIPOQ and SOX2 genetic polymorphisms are found to be associated with DN. In the present study, we first investigated the association between MCF2L2 and DN, and then evaluated effects of these three genes on the development of DN. METHODS: A total of 1177 type 1 diabetes patients with and without DN from the GoKinD study were genotyped with TaqMan allelic discrimination. All subjects were of European descent. RESULTS: Leu359Ile T/G variant in the MCF2L2 gene was found to be associated with DN in female subjects (P = 0.017, OR = 0.701, 95%CI 0.524-0.938) but not in males. The GG genotype carriers among female patients with DN had tendency decreased creatinine and cystatin levels compared to the carriers with either TT or TG genotypes. This polymorphism MCF2L2-rs7639705 together with SNPs of ADIPOQ-rs266729 and SOX2-rs11915160 had combined effects on decreased risk of DN in females (P = 0.001). CONCLUSION: The present study provides evidence that MCF2L2, ADIPOQ and SOX2 genetic polymorphisms have effects on the resistance of DN in female T1D patients, and suggests that the linkage with DN in chromosome 3q may be explained by the cumulated genetic effects.

摘要

背景：MCF2L2、ADIPOQ 和 SOX2 基因位于染色体 3q26-27 上，该区域与糖尿病肾病（DN）相关。ADIPOQ 和 SOX2 基因的遗传多态性与 DN 相关。本研究首次探讨了 MCF2L2 与 DN 的关系，并评估了这三个基因对 DN 发生发展的影响。

方法：采用 TaqMan 等位基因鉴别法对来自 GoKinD 研究的 1177 例有或无 DN 的 1 型糖尿病患者进行 MCF2L2 基因分型。所有受试者均为欧洲血统。

结果：MCF2L2 基因的 Leu359Ile T/G 变体与女性 DN 相关（P = 0.017，OR = 0.701，95%CI 0.524-0.938），但与男性无关。DN 女性患者中 GG 基因型携带者的肌酐和胱抑素水平较 TT 或 TG 基因型携带者有下降趋势。MCF2L2-rs7639705 多态性与 ADIPOQ-rs266729 和 SOX2-rs11915160 单核苷酸多态性的联合作用降低了女性发生 DN 的风险（P = 0.001）。

结论：本研究提供了证据表明 MCF2L2、ADIPOQ 和 SOX2 基因多态性对女性 1 型糖尿病患者 DN 的抗性有影响，并提示 3q 染色体上与 DN 的连锁可能是由累积的遗传效应所解释。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e69/2919463/45eb32436322/1471-2350-11-116-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e69/2919463/45eb32436322/1471-2350-11-116-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e69/2919463/45eb32436322/1471-2350-11-116-1.jpg

相似文献

[1]
Effects of MCF2L2, ADIPOQ and SOX2 genetic polymorphisms on the development of nephropathy in type 1 Diabetes Mellitus.

BMC Med Genet. 2010-7-28

[2]
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[2]
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[3]
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[4]
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[5]
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Diabetes Metab Syndr Obes. 2019-11-5

[6]
Effects of Apolipoprotein E Isoforms in Diabetic Nephropathy of Chinese Type 2 Diabetic Patients.

J Diabetes Res. 2017

[7]
A Meta-Analysis of Randomized Controlled Trials of Yiqi Yangyin Huoxue Method in Treating Diabetic Nephropathy.

Evid Based Complement Alternat Med. 2016

[8]
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BMC Med Genet. 2014-10-4

[9]
Trees Assembling Mann-Whitney approach for detecting genome-wide joint association among low-marginal-effect loci.

Genet Epidemiol. 2012-11-7

[10]
Association of eGFR-Related Loci Identified by GWAS with Incident CKD and ESRD.

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本文引用的文献

[1]
SOX2 has gender-specific genetic effects on diabetic nephropathy in samples from patients with type 1 diabetes mellitus in the GoKinD study.

Gend Med. 2009-12

[2]
Association of genetic variants at 3q22 with nephropathy in patients with type 1 diabetes mellitus.

Am J Hum Genet. 2009-1

[3]
Induced pluripotent stem cells generated without viral integration.

Science. 2008-11-7

[4]
Genetic association analyses of non-synonymous single nucleotide polymorphisms in diabetic nephropathy.

Diabetologia. 2008-11

[5]
A single nucleotide polymorphism alters the sequence of SP1 binding site in the adiponectin promoter region and is associated with diabetic nephropathy among type 1 diabetic patients in the Genetics of Kidneys in Diabetes Study.

J Diabetes Complications. 2009

[6]
High-density single nucleotide polymorphism genome-wide linkage scan for susceptibility genes for diabetic nephropathy in type 1 diabetes: discordant sibpair approach.

Diabetes. 2008-9

[7]
Small GTP-binding proteins and their regulators in cardiac hypertrophy.

J Mol Cell Cardiol. 2008-4

[8]
Search for type 2 diabetes susceptibility genes on chromosomes 1q, 3q and 12q.

J Hum Genet. 2008

[9]
Rho exchange factors in the cardiovascular system.

Curr Opin Pharmacol. 2008-4

[10]
Induction of pluripotent stem cells from adult human fibroblasts by defined factors.

Cell. 2007-11-30

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