研究报告

中国汉族人群ENPP1基因K121Q多态与2型糖尿病的关联及Meta分析

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  • 1. 华中师范大学生命科学学院, 遗传调控与整合生物学湖北省重点实验室, 武汉 430079; 2. 武汉医疗救治中心, 武汉 430022

收稿日期: 2009-11-24

  修回日期: 2009-12-22

  网络出版日期: 2010-07-23

基金资助

国家自然科学基金项目(编号:30340068)资助

Association and meta-analysis of ENPP1 K121Q with type 2 diabetes in Han Chinese

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  • 1. Hubei Key Lab of Genetic Regulation and Integrative Biology, College of Life Sciences, Central China Normal Univer-sity, Wuhan 430079, China; 2. Wuhan Center of Medical Therapeutics, Wuhan 430022, China

Received date: 2009-11-24

  Revised date: 2009-12-22

  Online published: 2010-07-23

摘要

多个欧洲白人的Meta分析表明核苷酸焦磷酸酶1(Ectonucleotide pyrophosphatase/phosphodiesterase 1, ENPP1)基因K121Q多态与2型糖尿病相关联, 但在日本人、韩国人和中国台湾人的研究中没有发现相关性, 而在中国大陆人群中二者的关联研究结果不尽一致。文章调查了湖北地区539例2型糖尿病患者和404名正常人ENPP1基因K121Q多态性。基因型及等位基因频率在病例组和对照组间没有显著差异(P>0.05), 但经性别、年龄和体重指数调整后的Logistic回归分析揭示XQ基因型与2型糖尿病显著相关(OR=1.5, 95%CI: 1.39~1.62, P<0.001)。对性别进行的亚组分析显示, 女性病例组Q等位基因和XQ基因型的频率显著高于对照组(Q: 12.4% vs. 6.1%, P=0.001; XQ: 23.7% vs. 11.7%, P=0.001)。结果表明ENPP1基因K121Q多态与湖北汉族人2型糖尿病的关联存在性别差异, 在女性中更明显。文章是对中国大陆人群进行的第一个Meta分析, 结果显示Q等位基因增加2型糖尿病的发病风险(OR=1.42, P=0.042)。

本文引用格式

王敏,彭婵,屈亚莉,黄青阳 . 中国汉族人群ENPP1基因K121Q多态与2型糖尿病的关联及Meta分析[J]. 遗传, 2010 , 32(8) : 808 -816 . DOI: 10.3724/SP.J.1005.2010.00808

Abstract

Multiple meta-analyses in Europeans showed that ENPP1 K121Q polymorphism was associated with type 2 diabetes. However, no association in Japanese, Korean, and Chinese in Taiwan, and inconsistent results in mainland Chinese were reported. In this study, the single nucleotide polymorphism K121Q of the ENPP1gene was genotyped in 539 type 2 diabetes patients and 404 healthy controls. No difference was observed in the genotypic and alle-lic frequencies of ENPP1 K121Q between the cases and the controls. Logistic regression analysis with adjustment of sex, age, and BMI suggested that the XQ genotype was significantly associated with the risk of type 2 diabetes (OR=1.5, 95%CI: 1.39–1.62, P<0.001). Sub-group analysis by gender revealed that the association between ENPP1 K121Q and type 2 diabetes was observed only in women (Q: 12.4% vs. 6.1%, P=0.001; XQ: 23.7% vs. 11.7%, P=0.001). Our results suggest that the association of ENPP1 K121Q with type 2 diabetes in Hubei Han Chinese population is more evident in women. The first meta-analysis of 10 Chinese studies indicated that the Q allele increased the risk of type 2 diabetes (OR=1.42, P=0.042).

参考文献

[1] 黄青阳, 程孟荣, 姬森林. 2型糖尿病易感基因的连锁和关联研究. 遗传学报, 2006, 33(7): 573–589. [2] Pizzuti A, Frittitta L, Argiolas A, Baratta R, Goldfine ID, Bozzali M, Ercolino T, Scarlato G, Iacoviello L, Vigneri R, Tassi V, Trischitta V. A polymorphism (K121Q) of the human glycoprotein PC-1 gene coding region is strongly associated with insulin resistance. Diabetes, 1999, 48(9): 1881–1884. [3] Costanzo BV, Trischitta V, Di Paola R, Spampinato D, Pizzuti A, Vigneri R, Frittitta L. The Q allele variant (GLN121) of membrane glycoprotein PC-1 interacts with the insulin receptor and inhibits insulin signaling more effectively than the common K allele variant (LYS121). Diabetes, 2001, 50(4): 831–836. [4] McAteer JB, Prudente S, Bacci S, Lyon HN, Hirschhorn JN, Trischitta V, Florez JC; ENPP1 Consortium. The ENPP1 K121Q polymorphism is associated with type 2 diabetes in European populations: evidence from an up-dated meta-analysis in 42,042 subjects. Diabetes, 2008, 57(4): 1125–1130. [5] Bacci S, Ludovico O, Prudente S, Zhang YY, Di Paola R, Mangiacotti D, Rauseo A, Nolan D, Duffy J, Fini G, Salvemini L, Amico C, Vigna C, Pellegrini F, Menzaghi C, Doria A, Trischitta V. The K121Q polymorphism of the ENPP1/PC-1 gene is associated with insulin resis-tance/atherogenic phenotypes, including earlier onset of type 2 diabetes and myocardial infarction. Diabetes, 2005, 54(10): 3021–3025. [6] Grarup N, Urhammer SA, Ek J, Albrechtsen A, Glümer C, Borch-Johnsen K, Jørgensen T, Hansen T, Pedersen O. Studies of the relationship between the ENPP1 K121Q polymorphism and type 2 diabetes, insulin resistance and obesity in 7,333 Danish white subjects. Diabetologia, 2006, 49(9): 2097–2104. [7] Weedon MN, Shields B, Hitman G, Walker M, McCarthy MI, Hattersley AT, Frayling TM. No evidence of associa-tion of ENPP1 variants with type 2 diabetes or obesity in a study of 8,089 U.K. Caucasians. Diabetes, 2006, 55(11): 3175–3179. [8] Keshavarz P, Inoue H, Sakamoto Y, Kunika K, Tanahashi T, Nakamura N, Yoshikawa T, Yasui N, Shiota H, Itakura M. No evidence for association of the ENPP1 (PC-1) K121Q variant with risk of type 2 diabetes in a Japanese population. J Hum Genet, 2006, 51(6): 559–566. [9] Seo HJ, Kim SG, Kwon OJ. The K121Q polymorphism in ENPP1 (PC-1) is not associated with type 2 diabetes or obesity in Korean male workers. J Korean Med Sci, 2008, 23(3): 459–464. [10] Chen MP, Chung FM, Chang DM, Tsai JC, Huang HF, Shin SJ, Lee YJ. ENPP1 K121Q polymorphism is not re-lated to type 2 diabetes mellitus, features of metabolic syndrome, and diabetic cardiovascular complications in a Chinese population. Rev Diabet Stud, 2006, 3(1): 21–30. [11] 徐梅, 王德全, 许玲, 唐宽晓, 司元国. 膜糖蛋白PC-1基因K121Q多态性与2型糖尿病相关性. 中华内分泌代谢杂志, 2003, 19(5): 390–391. [12] 刘茂玲. 2型糖尿病易感基因、环境危险因素及其交互作用研究[学位论文]. 华中科技大学, 2006, 1–118. [13] 芦鹭. PC-1基因K121Q多态性与2型糖尿病及肥胖相关性的研究[学位论文]. 大连医科大学, 2006, 1–37. [14] 李梅蕊, 吴于滨, 刘华, 王玉明, 冯霞, 宋滇平. PC-1基因多态性与2型糖尿病及糖尿病肾病的相关性研究. 昆明医学院学报, 2008, 1: 27–31. [15] 杜晓晖. 膜糖蛋白PC-1基因多态性与2型糖尿病及胰岛素抵抗关系的研究[学位论文]. 武汉大学, 2002, 1–41. [16] 任伟, 张素华, 吴静, 倪银星, 李全民. 2型糖尿病家系膜糖蛋白PC-1基因多态性的研究. 中华糖尿病杂志, 2004, 12(4): 246–249. [17] 于永春, 李智, 李晶华, 滕小洪, 汪纯, 赵敏. PC-1基因K121Q变异与2型糖尿病的关系. 检验医学, 2005, 20(4): 313–316. [18] 钟严伟, 高玲, 吴少庭, 耿艺介, 余英祥. PC-1基因K121Q多态性与2型糖尿病相关性研究. 中国热带医学, 2006, 6(12): 2113–2114. [19] 史晓红, 杨泽, 孙亮, 王沥, 金锋. 浆细胞膜糖蛋白基因K121Q变异与老年人2型糖尿病的关联研究. 中国老年保健医学, 2008, 6(5): 3–6. [20] 许曼音主编. 糖尿病学. 上海: 上海科学技术出版社. 2003, 17. [21] Hamaguchi K, Terao H, Kusuda Y, Yamashita T, Hazoury Bahles JA, Cruz LL M, Brugal V LI, Jongchong W B, Yoshimatsu H, Sakata T. The PC-1 Q121 allele is excep-tionally prevalent in the Dominican Republic and is asso-ciated with type 2 diabetes. J Clin Endocrinol Metab, 2004, 89(3): 1359–1364. [22] Abate N, Chandalia M, Satija P, Adams-Huet B, Grundy SM, Sand
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