Association of the intronic polymorphism rs12540874 A>G of the GRB10 gene with high birth weight

•The SNP r12540874 of GRB10 gene is associated with HBW in newborns at term.•The SNP rs12540874 impairs the insulin pathway.•The SNP rs12540874 is associated with prenatal hyperinsulinemia.•Although intronic, the SNP rs12540874 A>G alters the expression of the GRB10 gene.

BackgroundHigh birth weight (HBW) is considered a key predictor of the development of chronic diseases, such as Type 2 Diabetes (T2D). Foetal growth depends on many factors, among which placental function is critical. Some genes with expression in the placenta, such as GRB10, are known to be involved in the regulation of insulin receptor pathways and the size of mouse littermates.AimTo evaluate whether the intronic polymorphism rs12540874 A>G of the GRB10 gene is associated with HBW in term newborns.Study designA total of 51 healthy term newborns were enrolled in a nested case–control study. The case group was defined by the presence of HBW (n = 17) and the control group by newborns with normal birth weight (NBW n = 34). Maternal and foetal factors influencing HBW were considered as exclusion criteria. The polymorphism was determined through real-time PCR using TaqMan technology. Categorical variables were evaluated with descriptive statistics, and multivariate logistic regression analysis was used to evaluate the association between polymorphism and HBW.ResultsThe newborns in the case group had a longer gestation period (39.7 ± 1.0 and 38.8 ± 1.8 weeks) and higher insulin levels at birth (9.5 ± 4.0 and 5.7 ± 3.4 μU/mL) than the newborns in the control group. The multivariate regression analysis, adjusted for weeks of gestation, showed a significant association between the SNP rs12540874 A>G of the GRB10 gene with HBW (OR 4.9; CI95% 1.10–22.10 p = 0.02).ConclusionsOur results suggest that the SNP rs12540874 A>G, an intronic SNP of the gene GRB10, is associated with HBW.