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Abstract <p>An ethnically homogeneous sample of 3320 people (1656 patients with type 2 diabetes mellitus (T2D) and 1664 relatively healthy volunteers) was used to analyze the associations of six polymorphic variants rs3219493, rs3219489, rs3219487, rs3219484, rs3219472, and rs3219463 of the gene encoding the enzyme for repair of oxidative DNA damage of <i>MUTYH</i> with T2D. DNA samples were genotyped by real-time PCR using allele-specific fluorescent probes. The analysis of associations of <i>MUTYH</i> genotypes and haplotypes with T2D was performed using the PLINK and SNPStats programs, respectively. T2D was associated with SNP rs3219484 (OR = 1.34, 95% CI = 1.086–1.660, <i>P</i> = 0.0059) and haplotype <i>H3</i> rs3219493C-rs3219489C-rs3219487C-rs3219484T-rs3219472C-rs3219463C of the <i>MUTYH</i> gene (OR = 1.32, 95% CI = 1.08–1.62, <i>P</i> = 0.0071). Stratified analysis for sex and body mass index revealed that associations of rs3219484 and haplotype <i>H3</i> with an increased risk of T2D were found exclusively in males and individuals who were overweight and obese. In females, the rs3219493 and rs3219487 variants determined the age of disease manifestation: T2D in carriers of the rs3219493-G/G and rs3219487-T/T genotypes developed 9 years earlier compared to carriers of the rs3219493-C/C and rs3219487-C/C genotypes. The data obtained indicate for the first time the presence of sexual dimorphism in the association of the MutY-homologous DNA glycosylase of the <i>MUTYH</i> gene with the disease status and early onset of T2D.</p>

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Single Nucleotide Variant rs3219484 MUTYH as a Genetic Predictor of Type 2 Diabetes Mellitus

  • 期刊论文

  • 发表日期：

    2026年1月1日

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  • E. V. Semikina,
  • I. E. Azarova,
  • E. Yu. Alferova,
  • A. V. Polonikov

摘要

Abstract

An ethnically homogeneous sample of 3320 people (1656 patients with type 2 diabetes mellitus (T2D) and 1664 relatively healthy volunteers) was used to analyze the associations of six polymorphic variants rs3219493, rs3219489, rs3219487, rs3219484, rs3219472, and rs3219463 of the gene encoding the enzyme for repair of oxidative DNA damage of MUTYH with T2D. DNA samples were genotyped by real-time PCR using allele-specific fluorescent probes. The analysis of associations of MUTYH genotypes and haplotypes with T2D was performed using the PLINK and SNPStats programs, respectively. T2D was associated with SNP rs3219484 (OR = 1.34, 95% CI = 1.086–1.660, P = 0.0059) and haplotype H3 rs3219493C-rs3219489C-rs3219487C-rs3219484T-rs3219472C-rs3219463C of the MUTYH gene (OR = 1.32, 95% CI = 1.08–1.62, P = 0.0071). Stratified analysis for sex and body mass index revealed that associations of rs3219484 and haplotype H3 with an increased risk of T2D were found exclusively in males and individuals who were overweight and obese. In females, the rs3219493 and rs3219487 variants determined the age of disease manifestation: T2D in carriers of the rs3219493-G/G and rs3219487-T/T genotypes developed 9 years earlier compared to carriers of the rs3219493-C/C and rs3219487-C/C genotypes. The data obtained indicate for the first time the presence of sexual dimorphism in the association of the MutY-homologous DNA glycosylase of the MUTYH gene with the disease status and early onset of T2D.