Analyses of non-synonymous obesity risk alleles in SH2B1 (rs7498665) and APOB48R (rs180743) in obese children and adolescents undergoing a 1-year lifestyle intervention.

Association of obesity risk alleles of single nucleotide polymorphisms (SNPs) near or in the SH2B adaptor protein 1 gene (SH2B1) and increased body mass index (BMI) has been often described. A gene in close proximity, apolipoprotein B48 receptor gene (APOB48R), is tagged by the same SNP(s).We analyzed 454 overweight and obese children and adolescents (10.8±2.6 years, BMI-SDS 2.4±0.5; 55% girls) who completed a 1-year lifestyle intervention ('Obeldicks' program). Carriers of obesity risk alleles of non-synonymous SNPs in SH2B1 (rs7498665, Thr484Ala) or APOB48R (rs180743, Pro419Ala), as genotyped by TaqMan, were analysed for changes in anthropometrics (body-mass index (BMI), and standardized BMI (BMI-SDS)), blood pressure (systolic and diastolic) and plasma parameters (total cholesterol, LDL-cholesterol, HDL-cholesterol, triacylglycerides, glucose, insulin, and HOMA).We observed no evidence for an association of the obesity risk alleles to alterations in any of the analyzed phenotypes. Both mean BMI and BMI-SDS improved during the intervention independent of genotype. The mean systolic blood pressure was lowered and concentrations of HDL-cholesterol increased significantly.The obesity risk alleles of non-synonymous SNPs at SH2B1 and APOB48R have no strong effect on weight loss-related phenotypes in overweight children after a 1-year lifestyle intervention.

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