Evaluation of the role of FTO (rs9939609) and MC4R (rs17782313) gene polymorphisms in type 1 diabetes and their relation to obesity

Jan 10, 2024Journal of pediatric endocrinology & metabolism : JPEM

How common gene variations in FTO and MC4R relate to type 1 diabetes and obesity

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Abstract

A significant association with type 1 diabetes (T1D) development was found for the genotype and allele of the melanocortin 4 receptor (MC4R) (rs17782313).

The genotype and allele of the MC4R (rs17782313) may be linked to an increased risk of developing T1D.
The fat mass obesity-associated (FTO) (rs9939609) genotype and allele could also pose a risk for T1D development.
Certain genotypes of the MC4R (rs17782313) may offer protection against obesity.
The FTO (rs9939609) genotype and allele may also provide a protective effect against obesity.
In obese individuals, diabetic subjects showed significantly higher frequencies of the FTO (rs9939609) genotypes and the A allele compared to non-diabetics.

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OBJECTIVES: This study aims to explore the effects of fat mass obesity-associated (FTO) (rs9939609) and melanocortin 4 receptor (MC4R) (rs17782313) gene polymorphisms in children with type 1 diabetes (T1D) and their relation to obesity.

METHODS: Fat mass obesity-associated (FTO) (rs9939609) and melanocortin 4 receptor (MC4R) (rs17782313) gene polymorphisms were evaluated in 164 patients and 100 controls, and genotypes, alleles, and haplotype frequencies were compared between cases and controls.

RESULTS: A significant association with T1D development was found with the, andgenotypes and theallele ofrs17782313. In addition,andgenotypes and theallele ofrs9939609 may also be risky for T1D development. While theandgenotypes of rs17782313 may be protective against obesity development, thegenotype andallele ofrs9939609 may also be protective against obesity development. Regarding obese subjects, comparing diabetics vs. non-diabetic studied subjects,rs9939609,, andgenotypes and the A allele had significantly higher frequencies in T1D with a higher risk of developing T1D. However, conducting multivariable analysis using significant covariates in univariable analysis revealed that only earlier age of T1D onset, lower C-peptide, and thedominant model were considered independent predictors of obesity within T1D. TC, CC TC+CC C MC4R TA, AA, TA+AA A FTO TC TC+CC MC4R AA A FTO FTO TA, AA TA+AA MC4R

CONCLUSIONS: The role of both genes' polymorphisms on the pathogenesis and the outcome of T1D and obesity can help in understanding the pathogenesis of both diseases and their associations with each other's and may be used as novel therapeutic targets for both diseases.

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Evaluation of the role of FTO (rs9939609) and MC4R (rs17782313) gene polymorphisms in type 1 diabetes and their relation to obesity

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