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01.01.2007 | Short Communication

Common variants in the TCF7L2 gene are strongly associated with type 2 diabetes mellitus in the Indian population

verfasst von: G. R. Chandak, C. S. Janipalli, S. Bhaskar, S. R. Kulkarni, P. Mohankrishna, A. T. Hattersley, T. M. Frayling, C. S. Yajnik

Erschienen in: Diabetologia | Ausgabe 1/2007

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Abstract

Aims and hypothesis

India has the greatest number of diabetic subjects in any one country, but the genetic basis of type 2 diabetes mellitus in India is poorly understood. Common non-coding variants in the transcription factor 7-like 2 gene (TCF7L2) have recently been strongly associated with increased risk of type 2 diabetes in European populations. We investigated whether TCF7L2 variants are also associated with type 2 diabetes mellitus in the Indian population.

Materials and methods

We genotyped type 2 diabetes patients (n = 955) and ethnically matched control subjects (n = 399) by sequencing three single nucleotide polymorphisms (SNPs) (rs7903146, rs12255372 and rs4506565) in TCF7L2.

Results

We observed a strong association with all the polymorphisms, including rs12255372 (odds ratio [OR] 1.50 [95% CI = 1.24–1.82], p = 4.0 × 10⁻⁵), rs4506565 (OR 1.48 [95% CI = 1.24–1.77], p = 2.0 × 10⁻⁵) and rs7903146 (OR 1.46 [95% CI = 1.22–1.75], p = 3.0 × 10⁻⁵). All three variants showed increased relative risk when homozygous rather than heterozygous, with the strongest risk for rs12255372 (OR 2.28 [95% CI = 1.40–3.72] vs OR 1.43 [95% CI = 1.11–1.83]). We found no association of the TCF7L2 genotypes with age at diagnosis, BMI or WHR, but the risk genotype at rs12255372 was associated with higher fasting plasma glucose (p = 0.001), higher 2-h plasma glucose (p = 0.0002) and higher homeostasis model assessment of insulin resistance (HOMA-R; p = 0.012) in non-diabetic subjects.

Conclusions

Our study in Indian subjects replicates the strong association of TCF7L2 variants with type 2 diabetes in other populations. It also provides evidence that variations in TCF7L2 may play a crucial role in the pathogenesis of type 2 diabetes by influencing both insulin secretion and insulin resistance. TCF7L2 is an important gene for determining susceptibility to type 2 diabetes mellitus and it transgresses the boundaries of ethnicity.

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Titel: Common variants in the TCF7L2 gene are strongly associated with type 2 diabetes mellitus in the Indian population
verfasst von: G. R. Chandak
C. S. Janipalli
S. Bhaskar
S. R. Kulkarni
P. Mohankrishna
A. T. Hattersley
T. M. Frayling
C. S. Yajnik
Publikationsdatum: 01.01.2007
Verlag: Springer-Verlag
Erschienen in: Diabetologia / Ausgabe 1/2007
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-006-0502-2

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Common variants in the TCF7L2 gene are strongly associated with type 2 diabetes mellitus in the Indian population

Abstract

Aims and hypothesis

Materials and methods

Results

Conclusions

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Abstract

Aims and hypothesis

Materials and methods

Results

Conclusions

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