The rsl2255372(G/T) and rs7903146(C/T) polymorphisms of the TCF7L2 gene are associated with type 2 diabetes mellitus in Asian Indians

被引:97
作者
Bodhini, Dhanasekaran [1 ]
Radha, Venkatesan [1 ]
Dhar, Monalisa [1 ]
Narayani, Nagarajan [1 ]
Mohan, Viswanathan [1 ]
机构
[1] Madras Diabetes Res Fdn, Adv Ctr Genom Diabetes, ICMR, Dr Mohans Diabetes Specialities Ctr,Mol Genet Uni, Madras 600086, Tamil Nadu, India
来源
METABOLISM-CLINICAL AND EXPERIMENTAL | 2007年 / 56卷 / 09期
关键词
D O I
10.1016/j.metabol.2007.04.012
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
One thousand thirty-eight normal glucose-tolerant and 1031 type 2 diabetic subjects selected from the Chennai Urban Rural Epidemiology Study were genotyped using polymerase chain reaction-restriction fragment length polymorphism assay to investigate the association of rs12255372(G/T) and rs7903146(C/T) polymorphisms of the transcription factor 7-like 2 (TCF7L2) gene with type 2 diabetes mellitus in Asian Indians. The frequency of the "T" allele of both rs12255372(G/T) and rs7903146(C/T) polymorphisms was significantly higher in diabetic subjects (23% and 33%) compared to that in normal glucose-tolerant subjects (19% and 28%; P = .001 and P = .0001, respectively). Logistic regression analysis of the rs12255372(G/T) polymorphism showed that the odds ratio (adjusted for age, sex, and body mass index) was 1.56 (95% confidence interval [CI], 1.03-2.37; P = .034) for the TT genotype and 1.29 (95% CI, 1.06-1.58; P = .01 1) for the TG genotype when compared with the GG genotype. Adjusted odds ratios for the TT and TC genotypes of the rs7903146(C/T) polymorphism were found to be 1.50 (95% CI, 1.08-2.08; P = .013) and 1.44 (95% CI, 1.18-1.76; P = .0003), respectively, compared with the CC genotype. Normal glucose-tolerant subjects with the TT genotype of rs12255372(G/T) had significantly higher 2-hour plasma glucose levels (mean +/- SD, 6.1 +/- 1.4 mmol/L) than those with tile GG genotype (5.6 +/- 1.0 mmol/L, P = .011). Normal glucose-tolerant subjects with the TT genotype of rs7903146(C/T) polymorphism had significantly higher 2-hour plasma glucose levels (mean +/- SD, 6.0 +/- 1.3 mmol/L) than those with the CC genotype (5.6 +/- 1.0 mmol/L, P = .004). In conclusion, the T allele of the rs12255372(G/T) and rs7903146(C/T) polymorphisms of TCF7L2 gene confer susceptibility to type 2 diabetes mellitus in Asian Indians. (C) 2007 Elsevier Inc. All rights reserved.
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页码:1174 / 1178
页数:5
相关论文
共 25 条
[1]  
Alberti KGMM, 1998, DIABETIC MED, V15, P539, DOI 10.1002/(SICI)1096-9136(199807)15:7<539::AID-DIA668>3.0.CO
[2]  
2-S
[3]   The common PPARγ Pro12Ala polymorphism is associated with decreased risk of type 2 diabetes [J].
Altshuler, D ;
Hirschhorn, JN ;
Klannemark, M ;
Lindgren, CM ;
Vohl, MC ;
Nemesh, J ;
Lane, CR ;
Schaffner, SF ;
Bolk, S ;
Brewer, C ;
Tuomi, T ;
Gaudet, D ;
Hudson, TJ ;
Daly, M ;
Groop, L ;
Lander, ES .
NATURE GENETICS, 2000, 26 (01) :76-80
[4]   Transcription factor TCF7L2 genetic study in the French population -: Expression in human β-cells and adipose tissue and strong association with type 2 diabetes [J].
Cauchi, Stephane ;
Meyre, David ;
Dina, Christian ;
Choquet, Helene ;
Samson, Chantal ;
Gallina, Sophie ;
Balkau, Beverley ;
Charpentier, Guillaume ;
Pattou, Francois ;
Stetsyuk, Volodymyr ;
Scharfmann, Raphael ;
Staels, Bart ;
Fruhbeck, Gema ;
Froguel, Philippe .
DIABETES, 2006, 55 (10) :2903-2908
[5]   Common variants in the TCF7L2 gene are strongly associated with type 2 diabetes mellitus in the Indian population [J].
Chandak, G. R. ;
Janipalli, C. S. ;
Bhaskar, S. ;
Kulkarni, S. R. ;
Mohankrishna, P. ;
Hattersley, A. T. ;
Frayling, T. M. ;
Yajnik, C. S. .
DIABETOLOGIA, 2007, 50 (01) :63-67
[6]   Polymorphisms in the transcription factor 7-like 2 (TCF7L2) gene are associated with type 2 diabetes in the Amish -: Replication and evidence for a role in both insulin secretion and insulin resistance [J].
Damcott, Coleen M. ;
Pollin, Toni I. ;
Reinhart, Laurie J. ;
Ott, Sandra H. ;
Shen, Haiqing ;
Silver, Kristi D. ;
Mitchell, Braxton D. ;
Shuldiner, Alan R. .
DIABETES, 2006, 55 (09) :2654-2659
[7]   The inheritebasis odiabetes mellitus: Implications for the genetic analysis of complex traits [J].
Florez, JC ;
Hirschhorn, J ;
Altshuler, D .
ANNUAL REVIEW OF GENOMICS AND HUMAN GENETICS, 2003, 4 :257-291
[8]   TCF7L2 polymorphisms and progression to diabetes in the Diabetes Prevention Program [J].
Florez, Jose C. ;
Jablonski, Kathleen A. ;
Bayley, Nick ;
Pollin, Toni I. ;
de Bakker, Paul I. W. ;
Shuldiner, Alan R. ;
Knowler, William C. ;
Nathan, David M. ;
Altshuler, David .
NEW ENGLAND JOURNAL OF MEDICINE, 2006, 355 (03) :241-250
[9]  
FRIEDEWALD WT, 1972, CLIN CHEM, V18, P499
[10]   Large-scale association studies of variants in genes encoding the pancreatic β-cell KATP channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) confirm that the KCNJ11 E23K variant is associated with type 2 diabetes [J].
Gloyn, AL ;
Weedon, MN ;
Owen, KR ;
Turner, MJ ;
Knight, BA ;
Hitman, G ;
Walker, M ;
Levy, JC ;
Sampson, M ;
Halford, S ;
McCarthy, MI ;
Hattersley, AT ;
Frayling, TM .
DIABETES, 2003, 52 (02) :568-572