SUMO4基因多态性与2型糖尿病的关系

doi:10.3724/SP.J.1005.2012.00315

遗传 ›› 2012, Vol. 34 ›› Issue (3): 315-325.doi: 10.3724/SP.J.1005.2012.00315

SUMO4基因多态性与2型糖尿病的关系

蒲连美¹, 南楠¹, 杨泽², 金泽宁¹

1. 首都医科大学附属安贞医院心内科, 北京100029 2. 卫生部北京医院/卫生部北京老年医学研究所, 卫生部老年医学重点实验室, 北京100730

收稿日期:2011-09-08 修回日期:2011-10-18 出版日期:2012-03-20 发布日期:2012-03-25
通讯作者: 金泽宁 E-mail:jinzening@hotmail.com

Association between SUMO4 polymorphisms and type 2 diabetes mellitus

PU Lian-Mei¹, NAN Nan¹, YANG Ze², JIN Ze-Ning¹

1. Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China 2. The Key Laboratory of Geriatrics, Beijing Hospital & Beijing Institute of Geriatrics, Ministry of Health, Beijing 100730, China

Received:2011-09-08 Revised:2011-10-18 Online:2012-03-20 Published:2012-03-25

摘要/Abstract

摘要： 为了探讨北京汉族人群小泛素样修饰蛋白4(Small ubiquitin-like modifier 4, SUMO4)基因多态性与2型糖尿病(Type 2 diabetes mellitus, T2DM)的关系, 文章采用病例对照设计, 选取404例T2DM患者(T2DM组)以及年龄、性别匹配的500例健康对照者(Control组)作为研究对象, 应用聚合酶链反应-高分辨熔解曲线(PCR-HRM)技术结合测序验证法, 检测SUMO4基因3个单核苷酸多态性位点(rs237025、rs237024及rs600739)的基因型与等位基因分布情况, 比较T2DM组糖化血红蛋白(Hemoglobin A_1c, HbA_1c)在各基因型间的分布, 并进行单倍型分析。结果显示：①rs237025的G等位基因在T2DM组出现的频率更高(0.334 vs. 0.282, P =0.017); GA基因型携带者患T2DM的风险是AA基因型携带者的1.563倍(P=0.001; OR, 1.563; 95% CI, 1.189-2.053); 在显性模型(GG+GA vs. AA)分析中, G等位基因携带者(GG+GA)患T2DM的风险是AA基因型携带者的1.525倍(P =0.002; OR, 1.525; 95% CI, 1.169-1.989)。而rs237024和rs600739多态性未发现与T2DM的易感性相关(P >0.05)。②在T2DM组, rs237025的G等位基因携带者、rs237024的TT基因型携带者及rs600739的GG基因携带者具有较高的HbA_1c水平, 但各基因型携带者之间HbA_1c水平并无统计学差异(P >0.05)。③单倍型AAC、AGC及GGT与T2DM的易感性正相关(OR>1); 而单倍型AAT、GAC与T2DM的易感性负相关(OR<1)。据此得出结论：rs237025多态性与北京汉族人群T2DM的易感性相关, rs237024和rs600739多态性可能与T2DM的易感性不相关。

关键词: SUMO4, 多态性, 2型糖尿病, 单体型, 关联

Abstract: This study investigated the association between small ubiquitin-like modifier 4 (SUMO4) gene polymorphisms and type 2 diabetes mellitus (T2DM) in Chinese Han of Beijing area. Using the case-control method, we included 404 T2DM patients in T2DM group and 500 age- and gender- matched healthy subjects in control group. We detected the distribution of alleles and genotypes of the three single nucleotide polymorphisms (SNPs, rs237025, rs237024 and rs600739) with the polymerase chain reaction-high resolution melting curve (PCR-HRM) combined with gene sequencing, analysed the differences of glycosylated hemoglobin A1c (HbA1c) among different genotypes carriers in T2DM group, and conducted a haplotype analysis. In this study, the results showed that the frequency of the G allele of rs237025 was significantly higher in T2DM group than that of control group (0.334 vs. 0.282, P = 0.017). Compared with control group, the GA genotype carriers of T2DM patients had 1.563 times more susceptibility to T2DM [P =0.001; odds ratio (OR), 1.563; 95% confidence interval (CI), 1.189-2.053]. Meanwhile, the G allele carriers (GG+GA) of T2DM patients had 1.525 times more susceptibility to T2DM in the dominant model (GG+GA vs. AA, P = 0.002; OR,1.525; 95% CI,1.169-1.989). However, as for rs237024 and rs600739, no significant differences were found in the distribution of the genotypes and alleles between two groups (P >0.05).Although our study didn't observe any statistically significant results, we found that T2DM patients with GG and GA genotypes of rs237025, TT genotype of rs237024 and GG genotype of rs600739 had a higher level of HbA1c than counterparts in control group. In addition, the AAC, AGC and GGT haplotypes might contribute to susceptibility to T2DM (OR>1) , while the AAT and GAC haplotypes might be considered as protective factors against T2DM (OR<1). The results suggested that rs237025 polymorphisms was associated with susceptibility to T2DM, but rs237024 and rs600739 were not.

Key words: SUMO4, polymorphisms, type 2 diabetes mellitus, haplotype, association

蒲连美，南楠，杨泽，金泽宁. SUMO4基因多态性与2型糖尿病的关系[J]. 遗传, 2012, 34(3): 315-325.

PU Lian-Mei, NAN Nan, YANG Ze, JIN Ze-Ning. Association between SUMO4 polymorphisms and type 2 diabetes mellitus[J]. HEREDITAS, 2012, 34(3): 315-325.

参考文献

[1] Maedler K, Sergeev P, Ris F, Oberholzer J, Joller-Jemelka HI, Spinas GA, Kaiser N, Halban PA, Donath MY. Glu-cose-induced β cell production of IL-1β contributes to glucotoxicity in human pancreatic islets. J Clin Invest, 2002, 110(6): 851-860.
[2] Cai DS, Yuan MS, Frantz DF, Melendez PA, Hansen L, Lee J, Shoelson SE. Local and systemic insulin resistance resulting from hepatic activation of IKK-β and NF-κB. Nat Med, 2005, 11(2): 183-190.
[3] Schmid H, Boucherot A, Yasuda Y, Henger A, Brunner B, Eichinger F, Nitsche A, Kiss E, Bleich M, Gröne HJ, Nelson PJ, Schlöndorff D, Cohen CD, Kretzler M. Modular activation of nuclear factor-κB transcriptional programs in human diabetic nephropathy. Diabetes, 2006, 55 (11): 2993-3003.
[4] Li HY, Lindholm E, Almgren P, Gustafsson Å, Forsblom C, Groop L, Tuomi T. Possible human leukocyte antigen-mediated genetic interaction between type 1 and type 2 Diabetes. J Clin Endocrinol Metab, 2001, 86(2): 574-582.
[5] Wang CY, She JX. SUMO4 and its role in type 1 diabetes pathogenesis. Diabetes Metab Res Rev, 2008, 24(2): 93-102.
[6] Ji ZZ, Dai Z, Huang Y, Martins HA, Xu YC. Association of SUMO4 Met55Val variation with increased insulin resistance in newly diagnosed type 2 diabetes in a Chinese population. J Huazhong Univ Sci Technolog Med Sci, 2011, 31(3): 306-311.
[7] Lin HY, Li SL, Yu ML, Hsiao PJ, Hsieh MC, Lin KD, Wang CL, Wang TN, Shin SJ. Small ubiquitin-like modifier-4 Met55Val polymorphism is associated with glycemic control of Type 2 diabetes mellitus in Taiwan. J Endocrinol Invest, 2010, 33(6): 401-405.
[8] Noso S, Fujisawa T, Kawabata Y, Asano K, Hiromine Y, Fukai A, Ogihara T, Ikegami H. Association of small ubiquitin-like modifier 4 (SUMO4) variant, located in IDDM5 locus, with type 2 diabetes in the Japanese population. J Clin Endocrinol Metab, 2007, 92(6): 2358-2362.
[9] 季振中, 代喆, 徐焱成. 类泛素样蛋白4 M55V基因多态性与2型糖尿病及其相关因素的关系. 中华糖尿病杂志, 2010, 02(5): 344-348.
[10] Gundry CN, Dobrowolski SF, Martin YR, Robbins TC, Nay LM, Boyd N, Coyne T, Wall MD, Wittwer CT, Teng DHF. Base-pair neutral homozygotes can be discriminated by calibrated high-resolution melting of small amplicons. Nucleic Acids Res, 2008, 36(10): 3401-3408.
[11] Gordon D, Levenstien MA, Finch SJ, Ott J. Errors and linkage disequilibrium interact multiplicatively when computing sample sizes for genetic case-control association studies. Pac Symp Biocomput, 2003: 490-501.
[12] Gordon D, Finch SJ, Nothnagel M, Ott J. Power and sam-ple size calculations for case-control genetic association tests when errors are present: application to single nucleo-tide polymorphisms. Hum Hered, 2002, 54(1): 22-33.
[13] Lin HY, Wang CL, Hsiao PJ, Lu YC, Chen SY, Lin KD, Hsin SC, Hsieh MC, Shin SJ. SUMO4 M55V variant is associated with diabetic nephropathy in type 2 diabetes. Diabetes, 2007, 56(4): 1177-1180.
[14] Shimada T, Furukawa Y, Furuta H, Yasuda K, Matsuno S, Kusuyama A, Doi A, Nishi M, Sasaki H, Sanke T, Nanjo K. SUMO4 Met55Val polymorphism is associated with coronary heart disease in Japanese type 2 diabetes individuals. Diabetes Res Clin Pract, 2009, 85(1): 85-89.
[15] Spitz AF, Kanani H. Change in HbA_1c as a measure of quality of diabetes care. Diabetes Care, 2006, 29(5): 1183-1184, 1184-1185.
[16] Stratton IM, Adler AI, Neil HAW, Matthews DR, Manley SE, Cull CA, Hadden D, Turner RC, Holman RR. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): pro-spective observational study. BMJ, 2000, 321(7258): 405-412.
[17] 李斌, 李会芳, 王玉明, 周晰溪, 张娴, 宋滇平. SUMO4基因163 A/G多态性与2型糖尿病及糖尿病视网膜病变的相关性研究. 昆明医学院学报, 2010, 31(6): 4-6, 52.
[18] Fallah S, Jafarzadeh M, Hedayati M. No association of the SUMO4 polymorphism M55V variant in type 2 dia

编辑推荐

Metrics

www.chinagene.cn
备案号：京ICP备09063187号-4
总访问:,今日访问:,当前在线:

SUMO4基因多态性与2型糖尿病的关系

Association between SUMO4 polymorphisms and type 2 diabetes mellitus

PDF (PC)

可视化

被引次数

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

[1]	王雪倩, 张庆珍, 程鹏, 董婷婷, 李卫国, 周喆, 王升启. 中国汉族人群66个InDel基因座的遗传多态性[J]. 遗传, 2022, 44(4): 335-345.
[2]	吕承安, 王若然, 孟卓贤. 2型糖尿病进程中胰岛β细胞功能变化的分子机制[J]. 遗传, 2022, 44(10): 840-852.
[3]	曾之扬, 陆佳微, 曹希雅, 王芯悦, 李大力. 一种GLP-1过表达肠类器官构建的方法[J]. 遗传, 2021, 43(7): 694-703.
[4]	周子文, 王雪, 丁向东. 基于高密度SNP标记估计群体间遗传关联[J]. 遗传, 2021, 43(4): 340-349.
[5]	李以格, 张丹丹. 后GWAS时代结直肠癌致病SNP功能机制的研究进展[J]. 遗传, 2021, 43(3): 203-214.
[6]	孙一丹, 田子钊, 周伟, 李沫, 怀聪, 贺林, 秦胜营. 中国人群肝功能检测指标全基因组关联分析研究[J]. 遗传, 2021, 43(3): 249-260.
[7]	单婷玉, 施雯, 王翌婷, 曹孜怡, 汪保华, 方辉. 玉米盐胁迫相关性状全基因组关联分析及候选基因预测[J]. 遗传, 2021, 43(12): 1159-1169.
[8]	王浩宇, 胡渝涵, 曹悦岩, 朱强, 黄雨果, 李茜, 张霁. 基于全基因组数据的AI-SNPs筛选及大陆次级区域内群体遗传结构差异研究[J]. 遗传, 2021, 43(10): 938-948.
[9]	钱国清. 慢性阻塞性肺疾病全基因组关联研究进展[J]. 遗传, 2020, 42(9): 832-846.
[10]	曹岚, 李志强, 师咏勇, 刘赟. 端粒长度与2型糖尿病：孟德尔随机化研究与多基因风险评分分析[J]. 遗传, 2020, 42(9): 882-888.
[11]	王玉琢, 张一鸣, 董晓莲, 王学才, 朱建福, 王娜, 江峰, 陈跃, 姜庆五, 付朝伟. 2型糖尿病易感基因SNP位点对生活方式干预降低血糖应答效果的修饰效应[J]. 遗传, 2020, 42(5): 483-492.
[12]	周晨希, 李沫, 怀聪, 贺林, 秦胜营. 中国人群中抗结核药物引发肝损伤的易感基因标记研究[J]. 遗传, 2020, 42(4): 374-379.
[13]	梅志超, 位竹君, 于佳慧, 冀凤丹, 解莉楠. 多组学关联分析揭示表观等位基因在拟南芥环境适应性进化中的作用及机制[J]. 遗传, 2020, 42(3): 321-331.
[14]	张秀泉,王建,熊符,吕伟标,周远青,杨少民,张玉婷,田小燕,连蔚,徐湘民. 染色体10q24.31片段重复导致先天性缺指/缺趾畸形的一个家系致病机理分析[J]. 遗传, 2019, 41(8): 716-724.
[15]	梁文权,侯豫,赵存友. 精神分裂症相关单核苷酸多态性调控microRNA功能研究进展[J]. 遗传, 2019, 41(8): 677-685.