The rs12255372(G/T) and rs7903146(C/T) polymorphisms of the TCF7L2 gene are associated with type 2 diabetes mellitus in Asian Indians
Introduction
Although type 2 diabetes mellitus has a strong genetic basis, until recently, most candidate genes for type 2 diabetes mellitus have shown only modest effects and the associations have been inconsistent [1], [2]. Reproducible associations have been documented for the Pro12Ala polymorphism in the peroxisome proliferator–activated receptor (PPARG) gene and the E23K polymorphism in the KCNJ11 gene [3], [4]. Recently, Grant et al [5] reported that the transcription factor 7–like 2 (TCF7L2) gene was strongly associated with type 2 diabetes mellitus in Icelandic subjects. TCF7L2 encodes a transcription factor that plays a role in the Wnt signaling pathway, a key cell developmental and growth regulatory mechanism. Florez et al [6] reported that polymorphisms rs12255372 and rs7903146 in the TCF7L2 gene were associated with an increased risk of developing type 2 diabetes mellitus. Subsequent studies confirmed association of these polymorphisms with type 2 diabetes mellitus in British [7], US [8], Finnish [9], Amish [10], Scandinavian, Polish [11], French [12], Dutch Breda [13], European whites, migrant Asian Indian, Afro-Caribbean [14], northern Swedish [15], and German [16] populations. The rs7903146 polymorphism alone was found to be associated with type 2 diabetes mellitus in Japanese population [17]. India has the largest number of people with diabetes mellitus in the world [18]. Although the association of variants of the TCF7L2 gene and type 2 diabetes mellitus has been investigated in several studies among white populations, there is only one study from the western part of India [19]. Hence, we examined the association of the 2 most strongly associated single nucleotide polymorphisms (SNPs) of the TCF7L2 gene in almost all populations reported so far, the rs12255372 and rs7903146 polymorphisms, with type 2 diabetes mellitus in an Asian Indian population in southern India.
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Study subjects
A total of 2069 subjects, 1031 type 2 diabetic subjects and 1038 normal glucose tolerant (NGT) subjects, were selected from phase 2 and phase 3 of the Chennai Urban Rural Epidemiology Study (CURES), respectively. The methodology of the study has been published elsewhere [20]. Briefly, 26 001 adult subjects (>20 years of age) were recruited in phase 1 of the CURES using a systematic random sampling method covering the whole Chennai city. This included 1529 “self-reported” diabetic subjects. In
Clinical and biochemical characteristics of the study subjects
Table 1 shows the clinical and biochemical characteristics of the study subjects. The diabetic subjects were older compared with the NGT subjects (49 ± 10 and 41 ± 11 years, respectively; P < .0001). A comparison between diabetic subjects and NGT subjects showed that the age- and sex-adjusted mean ± SD of BMI (P < .0001), waist circumference (P < .0001), total cholesterol (P < .0001), serum triglycerides (P < .0001), and low-density lipoprotein cholesterol (P = .001) were significantly higher
Discussion
The important finding of this study is that the rs12255372 and rs7903146 SNPs are associated with type 2 diabetes mellitus in this Asian Indian population studied in southern India. The SNPs rs12255372 and rs7903146 showed the strongest association with type 2 diabetes mellitus in an Icelandic sample, and this association was confirmed in white samples from Denmark and the United States in the study by Grant et al [5]. All subsequent studies conducted on various other populations [7], [8], [9],
Acknowledgments
The study was supported by a grant from the Department of Biotechnology, New Delhi, India.
We express our gratitude to the Indian Council for Medical Research for nominating MDRF as an ICMR-Advanced Centre for Genomics of type 2 diabetes mellitus. We thank the Chennai Wellingdon Corporate Foundation for their support for the CURES field studies (CURES-42).
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