Combined effect of FTO and MC4R gene polymorphisms on obesity in children and adolescents in Northwest China: a case-control study.

BACKGROUND AND OBJECTIVES: Fat mass and obesity-associated (FTO) and melanocortin 4 receptor (MC4R) genes associated with obesity have been identified through Genome-wide Association Studies. However, no multiple loci interaction studies have been conducted in the Chinese population. This study investigated whether the combined effects of FTO and MC4R increase the risk of obesity in children and adolescents living in Northwest China. METHODS AND STUDY DESIGN: A total of 370 subjects (170 overweight/obese and 200 normal BMI subjects according to the Working Group on Obesity in China criteria) were enrolled using the random sampling method. FTO rs9939609 and rs9935401 and MC4R rs12970134 and rs17782313 interactions were analysed through generalized multifactor dimensionality reduction, and logistic regression models were used to calculate the risk of the relationship between genotypes and obesity. RESULTS: Generalized multifactor dimensionality reduction analysis showed a significant gene-gene interaction among FTO rs9939609/MC4R rs12970134/MC4R rs17782313, with a score of 10/10 for the cross-validation consistency and 9 for the sign test (p=0.011). A 2.453-fold increased risk of obesity was observed in individuals carrying the genotypes of FTO rs9939609 TA/AA, MC4R rs12970134 GA/AA, and MC4R rs17782313 TC/CC (adjusted for age, sex, and ethnicity; 95% CI=1.12-5.37, p=0.025). CONCLUSIONS: Our results suggested that FTO rs9939609, MC4R rs12970134, and MC4R rs17782313 are strongly associated with obesity. The combined effects were highly significant on obesity in children and adolescents living in Northwest China.