RETN、LEPR和ADIPOQ基因多态性与中国汉族人群2型糖尿病风险及血脂代谢的关系

doi:10.3969/j.issn.2095-9400.2019.11.005

摘要
图/表
参考文献
相关文章 (15)

全文: PDF (1237 KB) HTML (1 KB)
输出: BibTeX | EndNote (RIS)

摘要目的：探讨中国汉族人群中编码脂肪因子的抵抗素（RETN）、瘦素受体（LEPR）和脂联素（ADIPOQ）基因多态性与2型糖尿病（T2DM）的相关性及其对血脂代谢的影响。方法：入组526例T2DM患者和344例无糖尿病对照者，采用竞争性等位基因特异性PCR（KASP）技术检测RETN（rs1862513、rs3745367），LEPR（rs1137101、rs13306519、rs1805096）和ADIPOQ（rs1501299、rs2241766）的单核苷酸多态性（SNP）；并对RETN、LEPR和ADIPOQ基因多态性与T2DM发病风险间的关系以及各SNP基因型与血脂代谢间的关系进行统计学分析。结果：T2DM组中RETN rs1862513 GG基因型和G变异等位基因的频率均高于对照组，差异有统计学意义（42.0% vs. 30.0%，P=0.003；65.0% vs. 57.1%，P=0.001，OR=1.397，95%CI=1.140～1.712）；进一步将总研究人群按不同BMI分析发现，在BMI＜25 kg/m2中，T2DM组中RETN rs1862513 GG基因型频率明显高于对照组（42.8% vs. 31.0%，P=0.015）；进一步分析各基因型与血脂的关系发现，RETN rs3745367在BMI＜25 kg/m2时GG或AG基因型具有更低的高密度脂蛋白胆固醇（HDL）水平（P=0.018）；LEPR rs13306519在BMI≥25 kg/m2时CC或CG基因型具有更低的HDL水平（P=0.016）；ADIPOQ rs1501299在总研究人群中CC或AC基因型的甘油三酯（TG）水平显著高于AA基因型（P=0.044）。结论：RETN rs1862513 G等位基因可能与中国汉族人群T2DM的发病风险相关；ADIPOQ rs1501299 CC或AC基因型可能与高TG水平有关，RETN rs3745367 GG或AG基因型在非肥胖人群，LEPR rs13306519 CC或CG基因型在肥胖人群中可能与低HDL水平相关。

	服务
	把本文推荐给朋友
	加入我的书架
	加入引用管理器
	E-mail Alert
	RSS
	作者相关文章
	郑文文
	张杭
	周心禾
	洪莹
	庄飞
	吴宸炜
	陈霞
	何航辉
	苏悦
	郑超

关键词 ：抵抗素, 瘦素受体, 脂联素, 2型糖尿病, 基因多态性, 血脂代谢

Abstract：Objective: To investigate the association of resistin gene (RETN), leptin receptor gene (LEPR) and adiponectin gene (ADIPOQ) polymorphisms encoding adipokines with the risk of type 2 diabetes mellitus (T2DM) and the effect on lipid metabolism in Chinese Han population. Methods: A total of 526 T2DM patients and 344 nondiabetic controls were enrolled in our study. The single-nucleotide polymorphisms (SNPs) of RETN (rs1862513, rs3745367), LEPR (rs1137101, rs13306519, rs1805096) and ADIPOQ (rs1501299, rs2241766) were determined by the kompetitive allele specific PCR (KASP) technique. The association of RETN, LEPR and ADIPOQ polymorphisms with the risk of T2DM and the relationship between various SNP genotypes and lipid metabolism were applied by statistical methods. Results: The frequency of GG genotype and G variant allele of RETN rs1862513 in the T2DM group was higher than the control group, and the difference was statistically significant (42.0% vs. 30.0%, P=0.003; 65.0% vs. 57.1%, P=0.001, OR=1.397, 95%CI=1.140-1.712); Further analysis of the overall study population found that the frequency of RETN rs1862513 GG genotype in the T2DM group was visibly higher than the control group in the BMI<25 kg/m2 group after grouped by BMI (42.8% vs. 31.0%, P=0.015). Further analysis of the relationship between each genotype and lipid, RETN rs3745367 GG or AG genotype had lower high density lipoprotein cholesterol (HDL) level at BMI<25 kg/m2 (P=0.018); LEPR rs13306519 CC or CG genotype had lower HDL level at BMI≥25 kg/m2 (P=0.016). In the overall study population, ADIPOQ rs1501299 CC or AC genotype had higher triglyceride (TG) level than AA genotypes (P=0.044). Conclusion: RETN rs1862513 G allele may be associated with the risk of T2DM in Chinese Han population; ADIPOQ rs1501299 CC or AC genotype may be associated with high TG level, RETN rs3745367 GG or AG genotype in non-obesity and LEPR rs13306519 CC or CG genotype in obese people may be associated with low HDL level.

Key words： resistin leptin receptor adiponectin type 2 diabetes mellitus gene polymorphism lipid metabolism

收稿日期: 2018-10-14

通讯作者: 郑超，教授，主任医师，硕士生导师，Email：wallbb_1022@163.com。

作者简介: 郑文文（1992-），女，浙江温州人，硕士生。

链接本文:

https://xb.wmu.edu.cn/CN/10.3969/j.issn.2095-9400.2019.11.005 或 https://xb.wmu.edu.cn/CN/Y2019/V49/I11/807

[1] KOLEVA D I, ORBETZOVA M M, ATANASSOVA P K. Adipose tissue hormones and appetite and body weight regulators in insulin resistance[J]. Folia Med (Plovdiv), 2013, 55(1): 25-32.
[2] BILIR B E, GULDIKEN S, TUNCBILEK N, et al. The effects of fat distribution and some adipokines on insulin re-sistance[J]. Endokrynol Pol, 2016, 67(3): 277-282.
[3] STEPPAN C M, BAILEY S T, BHAT S, et al. The hormone resistin links obesity to diabetes[J]. Nature, 2001, 409 (6818): 307-312.
[4] SMITH S R, BAI F, CHARBONNEAU C, et al. A promoter genotype and oxidative stress potentially link resistin to human insulin resistance[J]. Diabetes, 2003, 52(7): 1611-1618.
[5] KUNNARI A, UKKOLA O, KESANIEMI Y A. Resistin polymorphisms are associated with cerebrovascular disease in Finnish Type 2 diabetic patients[J]. Diabet Med, 2005, 22(5): 583-589.
[6] OSAWA H, ONUMA H, MURAKAMI A, et al. Systematic search for single nucleotide polymorphisms in the resistin gene: the absence of evidence for the association of three identified single nucleotide polymorphisms with Japanese type 2 diabetes[J]. Diabetes, 2002, 51(3): 863-866.
[7] SENTINELLI F, ROMEO S, ARCA M, et al. Human resistin gene, obesity, and type 2 diabetes: mutation analysis and population study[J]. Diabetes, 2002, 51(3): 860-862.
[8] HOLCOMB I N, KABAKOFF R C, CHAN B, et al. FIZZ1, a novel cysteine-rich secreted protein associated with pulmonary inflammation, defines a new gene family[J]. EMBO J, 2000, 19(15): 4046-4055.
[9] CAMMISOTTO P G, BENDAYAN M. Leptin secretion by white adipose tissue and gastric mucosa[J]. Histol Histopathol, 2007, 22(2): 199-210.
[10] FLIER J S. Hormone resistance in diabetes and obesity: insulin, leptin, and FGF21[J]. Yale J Biol Med, 2012, 85(3): 405-414.
[11] STEFAN N, VOZAROVA B, DELP A, et al. The Gln223Arg polymorphism of the leptin receptor in Pima Indians: influence on energy expenditure, physical activity and lipid metabolism[J]. Int J Obes Relat Metab Disord, 2002, 26(12): 1629-1632.
[12] ZHANG F, CHEN Y, HEIMAN M, et al. Leptin: structure, function and biology[J]. Vitam Horm, 2005, 71: 345-372.
[13] HEID I M, WAGNER S A, GOHLKE H, et al. Genetic architecture of the APM1 gene and its influence on adiponectin plasma levels and parameters of the metabolic syndrome in 1,727 healthy Caucasians[J]. Diabetes, 2006, 55(2): 375-384.
[14] ZIEMKE F, MANTZOROS C S. Adiponectin in insulin resistance: lessons from translational research[J]. Am J Clin Nutr, 2010, 91(1): 258S-261S.
[15] HIVERT M F, MANNING A K, MCATEER J B, et al. Association of variants in RETN with plasma resistin levels and diabetes-related traits in the Framingham Offspring Study [J]. Diabetes, 2009, 58(3): 750-756.
[16] HAN H R, RYU H J, CHA H S, et al. Genetic variations in the leptin and leptin receptor genes are associated with type 2 diabetes mellitus and metabolic traits in the Korean female population[J]. Clin Genet, 2008, 74(2): 105-115.
[17] WAUTERS M, CONSIDINE R V, CHAGNON M, et al. Leptin levels, leptin receptor gene polymorphisms, and energy metabolism in women[J]. Obes Res, 2002, 10(5): 394-400.
[18] VASSEUR F, MEYRE D, FROGUEL P. Adiponectin, type 2 diabetes and the metabolic syndrome: lessons from human genetic studies[J]. Expert Rev Mol Med, 2006, 8(27): 1-12.
[19] BOUCHARD L,WEISNAGEI S J, ENGERT J C, et al. Human resistin gene polymorphism is associated with visceral obesity and fasting and oral glucose stimulated C-peptide in the Quebec Family Study[J]. J Endocrinol Invest, 2004, 27(11): 1003-1009.
[20] MA X, WARRAM J H, TRISCHITTA V, et al. Genetic variants at the resistin locus and risk of type 2 diabetes in Cau-casians[J]. J Clin Endocrinol Metab, 2002, 87(9): 4407-4410.
[21] OSAWA H, YAMADA K, ONUMA H, et al. The G/G genotype of a resistin single-nucleotide polymorphism at-420 increases type 2 diabetes mellitus susceptibility by inducing promoter activity through specific binding of Sp1/3[J]. Am J Hum Genet, 2004, 75(4): 678-686.
[22] OCHI M, OSAWA H, HIROTA Y, et al. Frequency of the G/G genotype of resistin single nucleotide polymorphism at-420 appears to be increased in younger-onset type 2 diabetes [J]. Diabetes, 2007, 56(11): 2834-2838.
[23] 宁冬平, 朱惠娟, 阳洪波, 等. 脂肪因子与肥胖及代谢综合征的相关研究进展[J]. 医学综述, 2018, 24(18): 3653-3657.
[24] ZHOU Q, CHEN B, JI T, et al. Association of genetic variants in RETN, NAMPT and ADIPOQ gene with glycemic, metabolic traits and diabetes risk in a Chinese popula-tion[J]. Gene, 2018, 642: 439-446.
[25] BECER E, MEHMETCIK G, BAREKE H, et al. Association of leptin receptor gene Q223R polymorphism on lipid profiles in comparison study between obese and non-obese subjects[J]. Gene, 2013, 529(1): 16-20.
[26] TURECK L V, LEITE N, SOUZA R L, et al. ADIPOQ single nucleotide polymorphism: Association with adiponectin and lipoproteins levels restricted to men[J]. Meta Gene, 2015, 5: 98-104.