The transcription factor 7-like 2 (TCF7L2) rs7903146 T allele was associated with type 2 diabetes (T2D) in most populations worldwide. In individuals of European descent, the association with T2D was recently found to be modulated by obesity status. However, further studies are necessary to clarify if whether interaction exists among subjects of non-European descent. In the present study, we analyzed the association of rs7903146 with T2D in 90 nonobese (Body Mass Index [BMI] <25kg/m(2)), 171 overweight (25≤BMI<30kg/m(2)) et 98 obese (BMI≥30kg/m(2)) individuals from Tunisia. The T allele was nominally associated with T2D in nonobese subjects (Odds Ratio [OR]=3.24 [1.10-9.53], P=0.021) whereas no effect was detected in overweight (P=0.3) and obese (P=0.22) individuals. Consequently, the same risk allele decreased susceptibility to obesity in T2D subjects (OR=0.47 [0.23-0.94], P=0.029) but not in normoglycemic controls (P=0.44). When analyzed all together, no allelic association was observed with T2D (P=0.20) whereas an artefactual association with decreased obesity (0.59 [0.38-0.90], P=0.013) was detected. As in Europeans, TCF7L2 is therefore not a risk factor for obesity in Tunisians, but its effect on T2D risk is modulated by obesity. In conclusion, the TCF7L2 rs7903146 T allele is nominally associated with T2D susceptibility in nonobese individuals from Tunisia.
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