Association of MC4R rs17782313 and multi-locus genetic variants with metabolic syndrome in Northern Vietnamese children aged 6–11 years: an exploratory study

Abstract Objectives Metabolic syndrome (MetS) is a multifactorial disorder associated with increased cardiometabolic risk. This exploratory study aimed to investigate the associations between five candidate single nucleotide polymorphisms (SNPs) and their haplotypes with MetS in children aged 6–11 years from Northern Vietnam. Methods A total of 547 children aged 6–11 years were included, comprising 39 children with MetS and 508 controls. MetS was defined using age-specific criteria based on modified International Diabetes Federation and National Cholesterol Education Program definitions. Genotyping of APOE -rs429358, APOE -rs7412, FTO -rs6499640, MC4R -rs17782313, and TMEM18 -rs6548238 was performed using polymerase chain reaction–restriction fragment length polymorphism analysis. Multivariable logistic regression adjusted for age, sex, and region was applied. Results MC4R -rs17782313 showed a significant associated with MetS. Under the recessive model, the C/C genotype was associated with increased MetS likelihood after adjustment (OR=2.28, p=0.005). A log-additive association was also observed (OR=2.03, p=0.014). No significant associations were detected for the other SNPs. Haplotype analysis suggested that three five-locus combinations were associated with higher MetS risk compared with the most common haplotype (T–C–G–T–C) (all p<0.05). Conclusions These findings suggest that MC4R rs17782313 may contribute to MetS susceptibility in this population. Given the limited number of MetS cases, results should be interpreted cautiously and require validation in larger pediatric cohorts and mechanistic studies.