Common polymorphisms in MC4R and FTO genes are associated with BMI and metabolic indicators in Mexican children: Differences by sex and genetic ancestry

Jun 8, 2020Gene

Common MC4R and FTO gene variants linked to body weight and metabolism in Mexican children, varying by sex and ancestry

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Abstract

The prevalence of certain gene variants associated with obesity is significantly higher in Mexican children with European ancestry compared to those with Amerindian ancestry.

High triglycerides and low HDL cholesterol were the most common metabolic issues identified in the study participants.
Significant associations were found between specific variants in the FTO and MC4R genes and obesity in boys.
Children with the AA genotype of SNPs rs8050136 and rs9939609 exhibited higher triglyceride levels compared to those with native ancestral genotypes.
The findings suggest that genetic ancestry may influence the distribution of obesity-related genetic variants in Mexican children.

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BACKGROUND: Mexico is experiencing an epidemic of childhood obesity and overweight, the factors that determine type 2 diabetes and cardiovascular diseases. Even though variants in genes such as MC4R, LEP, LEPR, and FTO have been associated with the risk of obesity, in Mexico the level of miscegenation is heterogeneous, so this risk must be measured as genetic ancestry. This study aimed at evaluating the association between common SNPs in FTO and MC4R genes in Mexican children with Amerindian, mestizo and predominance European ancestry.

METHODS: Anthropometric data and fasting blood samples were collected from 718 unrelated Mexican school children aged 4-13 years old. Variants in the FTO, MC4R, LEP, LEPR genes and 15 ancestry informative markers (AIMs), were genotyped using allelic discrimination assays.

RESULTS: High triglycerides and low cholesterol HDL were the most frequent metabolic alterations. The prevalence of minor allele frequency of polymorphism rs8050136, rs9939609, and rs3751812 in the FTO gene; and rs17782313 of MC4R gene were found to be significantly higher among Mexican children with a predominance of European ancestry (EA) compared to native Mexican children (Amerindian predominance), Xtest, p < 0.05. The FTO (rs8050136, rs9939609) and MC4R (rs17782313) genotypes also were significantly associated with obesity (BMI > 2Z) in boys (OR=1.89, P=0.04, OR=3.3, P=0.006 OR=3.11, p=0.04, respectively). Children with AA genotype (minor) of rs8050136 and rs9939609 SNPs have higher triglycerides in relation to native ancestral genotypes. 2

CONCLUSION: Risk variants in the FTO and MC4R genes had a higher frequency in children with EA compared with Amerindian predominance children, showing that miscegenation is associated with the frequency of obesity-related genotypes.

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Common polymorphisms in MC4R and FTO genes are associated with BMI and metabolic indicators in Mexican children: Differences by sex and genetic ancestry

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