Association of obesity and menarche SNPs and interaction with environmental factors on precocious puberty

Pediatr Res. 2024 Sep;96(4):1076-1083. doi: 10.1038/s41390-024-03168-6. Epub 2024 Apr 22.

Abstract

Background: Obesity is an important cause for the precocious or early puberty. However, the association between obesity-related loci and the risk of precocious puberty as well as the effect of gene-environment interaction are unclear, especially in the Chinese children population.

Methods: This was a case-control study using baseline data from two cohorts and hospital cases in China. 15 SNPs loci and several environmental factors were included in the analysis of 1201 participants. Chi-square test and logistic regression were used to analyze the association between SNPs and precocious puberty. Additionally, exploratory factor analysis was conducted on 13 environmental variables, and then to explore their interaction with genes on precocious puberty.

Results: The effect allele C of rs571312, and G of rs12970134 MC4R were associated with precocious puberty in girls with obesity. Regarding the gene-environment interaction, we found that when girls were in the high socioeconomic status, the rs571312 (OR: 3.996; 95% CI: 1.694-9.423) and rs12970134 (OR: 3.529; 95% CI: 1.452-8.573) risk genotypes had a greater effect on precocious puberty.

Conclusions: The obesity risk gene polymorphisms MC4R rs571312 and rs12970134 were associated with precocious puberty in Chinese girls with obesity, and girls with risk genotypes and high socioeconomic status should be given extra attention.

Impact: This is the first study that identified the association between rs571312 and rs12970134 of MC4R gene and precocious puberty in Chinese children. We found that when girls were in the high socioeconomic status, the risk genotypes of rs571312 and rs12970134 had a greater effect on precocious puberty. The results of this study have great public health implications. It is recommended that girls who are in high socioeconomic status and have a high genetic risk for early sexual maturity should closely monitor their pubertal development and consider early intervention strategies.

MeSH terms

  • Alleles
  • Case-Control Studies
  • Child
  • China
  • East Asian People / genetics
  • Female
  • Gene-Environment Interaction*
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Menarche* / genetics
  • Obesity / genetics
  • Pediatric Obesity / genetics
  • Polymorphism, Single Nucleotide*
  • Puberty, Precocious* / genetics
  • Receptor, Melanocortin, Type 4* / genetics
  • Risk Factors

Substances

  • MC4R protein, human
  • Receptor, Melanocortin, Type 4