TCF7L2 rs7903146 variant does not associate with smallness for gestational age in the French population

Background: In adults, the TCF7L2 rs7903146 T allele, commonly associated with type 2 diabetes ( T2D), has been also associated with a lower body mass index ( BMI) in T2D individuals and with a smaller waist circumference in subjects with impaired glucose tolerance. Methods: The present association study aimed at analyzing the contribution of the rs7903146 SNP to smallness for gestational age ( SGA) and metabolic profiles in subjects with SGA or appropriate for gestational age birth weight ( AGA). Two groups of French Caucasian subjects were selected on birth data: SGA ( birth weight < 10(th) percentile; n = 764), and AGA ( 25(th) < birth weight < 75(th) percentile; n = 627). Family- based association tests were also performed in 3,012 subjects from 628 SGA and AGA pedigrees. Results: The rs7903146 genotypic distributions between AGA ( 30.7%) and SGA ( 29.0%) were not statistically different ( allelic OR = 0.92 [ 0.78 - 1.09], p = 0.34). Family association- based studies did not show a distortion of T allele transmission in SGA subjects ( p = 0.52). No significant effect of the T allele was detected on any of the metabolic parameters in the SGA group. However, in the AGA group, trends towards a lower insulin secretion ( p = 0.03) and a higher fasting glycaemia ( p = 0.002) were detected in carriers of the T allele. Conclusion: The TCF7L2 rs7903146 variant neither increases the risk for SGA nor modulates birth weight and young adulthood glucose homeostasis in French Caucasian subjects born with SGA.