Individual genetic variations of eight SNPs associated with risk of obesity in preschool age children from STRONG Kids Program

Background. Childhood obesity is a severe public health problem in the United States. The STRONG Kids Program was designed to identify risk factors for excessive weight gain and obesity development in preschool-age children based on the ecological framework of the six Cs’ model. Increased food intake, which is one of the critical factors leading to the onset of obesity has been strongly associated with genetic predisposition. Variations in genes involved or potentially related to the leptin-melanocortin pathway (i.e. BDNF, FTO, LEP, LEPR, MC4R, PCSK1, POMC, TUB) have been associated with symptoms of poor appetite control and obesity-related phenotypes. Hypothesis. Individual genetic variations related to satiety and appetite control in the BDNF, FTO, LEP, LEPR, MC4R, PCSK1, POMC, and TUB genes are associated with the risk of obesity in preschool-age children. Objectives. The objectives of the current study are: (1) to investigate the association between obesity related phenotypes and genetic variations; (2) to investigate the association between genetic variations with satiety and appetite control; (3) to investigate the association between the obesity phenotypes and satiety and appetite control. Methods. Height and weight were measured in 128 Caucasian preschool children from the STRONG Kids Program (age 39.9 + 2.0 months, BMI 16.5 + 1.2 kg/m2). Genomic DNA was extracted from saliva samples and used for genotyping. Eight SNPs rs925946, rs1137101, rs8057044, rs6235, rs934778, rs2272382, rs7799039 and rs17782313 within or near the BDNF, LEPR, FTO, PCSK1, POMC, TUB, LEP, MC4R genes were genotyped by either FP-TDI assay or TaqMan SNP genotyping assay. Statistical analyses were performed with SAS 9.2 and p-link iii software to test the association between genotype and anthropometric data, and to calculate the genetic scores. Results. In this cohort, 25 children (19.5%) were overweight and 8 children (6.3%) were obese. There were significant associations between the height-for-age z-score and the rs2272382 SNP on TUB (P=0.0021) after adjusting for breastfeeding duration. The SNP rs17782313 in the MC4R gene also showed significant association with height-for-age z-score (P=0.038) before, but not after, adjusting for breastfeeding duration. As the number of risk allele increases, the risk of being obese or showing the first signs of being obese also increases. The responses to question seven in the survey (when this child gets fussy, is giving him/her something to eat or drink the first thing you do?) was significantly linked with rs925946 (P=0.0317). The responses of ‘Restriction for Weight Control’ (cluster 11) were significantly associated with BMI (P=0.049). The ‘Restriction for Health’ (cluster 10) showed a borderline significant association with CDC weight-for-age z-score (P=0.0567). Conclusion. Our observation suggest that genetic variants on TUB, MC4R, BDNF and LEP are related to the risk of obesity in our cohort; as the number of risk alleles increases, the risk of early-onset obesity increases. Preliminary data showed an association between genetic variations and satiety and appetite control, and an association between the obesity phenotypes and satiety and appetite control. Further modifications of the survey and questions are still needed