Original articleTCF7L2 is associated with type 2 diabetes in nonobese individuals from TunisiaTCF7L2 est associé au diabète de type 2 chez les non-obèses de Tunisie
Introduction
Type 2 diabetes (T2D) involves a complex interaction between genetic and environmental factors with obesity established as a primary risk factor [1]. Variations within intron 3 of the transcription factor 7-like 2 (TCF7L2) gene were initially associated with increased risk for T2D in populations of European descent [2]. Then, Helgason et al. reported that the rs7903146 T allele may be the etiological ancestral allele [3]. This Single Nucleotide Polymorphism (SNP) has therefore been the best proxy to evaluate the effect of this gene on T2D risk in additional ethnic groups. The rs7903146 T allele has then been consistently associated with T2D in most ethnicities [4] and has been the SNP the most associated with T2D in Genome Wide Association Studies (GWAS) of Caucasian populations [5], [6], [7], [8], [9]. However, in populations of European descent, the rs7903146 T allele was also associated with lower Body Mass Index (BMI) in T2D individuals and with a higher risk for T2D in nonobese subjects [3], [10], [11], [12]. In developing countries that have been adopting a western lifestyle involving decreased physical activity and overconsumption of cheap, energy-dense food, the rates of obesity have tripled [13]. In Tunisia, according to the National Nutrition Survey 1996/97, the prevalence of obesity reaches 22,7% in women and 6,4% in men. We previously showed that TCF7L2 is strongly associated with T2D in Moroccans [4] but we needed to see if one could confirm such association in another population from the Maghreb and clarify if similar interactions with BMI exists in non-Europeans. In the present study, we first analyzed the association of the rs7903146 T allele with T2D in 90 nonobese (BMI < 25 kg/m2), 171 overweight (25 ≤ BMI < 30 kg/m2) and 98 obese (BMI ≥ 30 kg/m2) individuals from Tunisia. Then, in the same individuals, the effects of TCF7L2 on obesity prevalence were assessed in control and T2D subjects.
Section snippets
Subjects
The study design included 359 subjects. Their phenotypic characteristics are summarized in Table 1. Participants originated from north of Tunisia were recruited in the Endocrinology service at Charles Nicolle's hospital in Tunis and among members working in the Tunisian society of electricity and gas at Tunis. All participants signed an informed consent and our protocol was approved by local ethic committees.
Measures
BMI is defined as the individual's body weight (kg) divided by the square of their
Discussion
In Europeans, it was recently suggested that genetic variants modulating insulin action may have an increased effect on T2D susceptibility in the presence of obesity, whereas genetic variants acting on insulin secretion may have a greater impact on T2D susceptibility in nonobese individuals [14]. An interaction between TCF7L2 and adiposity may be due to better β-cell compensation in obese individuals [15], [16].
In the present study, we found that TCF7L2 is nominally associated with T2D
References (16)
- et al.
Prevalence of obesity, diabetes, and obesity related health risk factors, 2001
Jama
(2003) - et al.
Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes
Nat Genet
(2006) - et al.
Refining the impact of TCF7L2 gene variants on type 2 diabetes and adaptive evolution
Nat Genet
(2007) - et al.
TCF7L2 is reproducibly associated with type 2 diabetes in various ethnic groups: a global meta-analysis
J Mol Med
(2007) - et al.
A Genome Wide Association Study identifies novel risk loci for type 2 diabetes
Nature
(2007) - et al.
A Genome Wide Association Study of type 2 diabetes in Finns detects multiple susceptibility variants
Science
(2007) - et al.
Genome wide association analysis identifies loci for type 2 diabetes and triglyceride levels
Science
(2007) - et al.
Replication of genome wide association signals in UK samples reveals risk loci for type 2 diabetes
Science
(2007)
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