Genetic variations in adiponectin levels and dietary patterns on metabolic health among children with normal weight versus obesity: the BCAMS study

Background/objectives Adiponectin represents an important link between adipose tissue dysfunction and cardiometabolic risk in obesity; however, there is a lack of data on the effects of adiponectin-related genetic variations and gene-diet interactions on metabolic disorders in children. We aimed to investigate possible interactions between adiponectin-related genetic variants and habitual dietary patterns on metabolic health among children with normal weight versus overweight/obesity, and whether these effects in childhood longitudinally contribute to metabolic risk at follow-up. Subjects/methods In total, 3,317 Chinese children aged 6–18 at baseline and 339 participants at 10-year follow-up from the Beijing Child and Adolescent Metabolic Syndrome study cohort were included. Baseline lifestyle factors, plasma adiponectin levels, and six adiponectin-related genetic variants resulting from GWAS in East Asians (loci in/near ADIPOQ, CDH13, WDR11FGF, CMIP , and PEPD ) were assessed for their associations with the metabolic disorders. Being metabolically unhealthy was defined by exhibiting any metabolic syndrome component. Results Among the six loci, ADIPOQ rs6773957 (OR 1.26, 95% CI:1.07–1.47, P = 0.004) and adiponectin receptor CDH13 rs4783244 (0.82, 0.69–0.96, P = 0.017) were correlated with metabolic risks independent of lifestyle factors in normal-weight children, but the associations were less obvious in those with overweight/obesity. A significant interaction between rs6773957 and diet ( P interaction = 0.004) for metabolic health was observed in normal-weight children. The adiponectin-decreasing allele of rs6773957 was associated with greater metabolic risks in individuals with unfavorable diet patterns ( P < 0.001), but not in those with healthy patterns ( P > 0.1). A similar interaction effect was observed using longitudinal data ( P interaction = 0.029). Conclusions These findings highlight a novel gene-diet interaction on the susceptibility to cardiometabolic disorders, which has a long-term impact from childhood onward, particularly in those with normal weight. Personalized dietary advice in these individuals may be recommended as an early possible therapeutic measure to improve metabolic health.