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<p>This study is aimed to examine the association between three variants of the <i>FMO3</i> gene—rs2266782G/A (E158K), rs2266780A/G (E308G), and rs1736557G/A (V257M)—and susceptibility to type 2 diabetes mellitus (T2DM), given the role of flavin-containing dimethylaniline monooxygenases (FMOs) in catalyzing trimethylamine N-oxide (TMAO), a compound linked to T2DM. A total of 800 adults were genotyped using PCR–RFLP or ARMS-PCR techniques, and various metabolic parameters, including lipid profiles and fasting blood sugar levels, were recorded for each participant. The findings revealed a significant association between the rs1736557 variant and T2DM under multiple inheritance models. Notably, the A allele of rs1736557 and the G allele of rs2266780 were associated with a decreased risk of T2DM, with risk reductions of 38% and 25%, respectively. Some genotype combinations exhibited a negative correlation with T2DM susceptibility, while certain haplotypes correlated with an increased risk of the disease. Bioinformatics analyses indicated that these genetic variants did not alter the secondary structure of FMO3 mRNA. Ultimately, the study identified significant associations between specific <i>FMO3</i> variations and T2DM risk, emphasizing the need for further research with diverse populations to validate these findings.</p> Graphical Abstract <p></p>

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Decoding the Link: Exploring FMO3 Gene Variations as a Key to Understanding Type Two Diabetes Through Bioinformatics and Case–Control Analyses

  • 期刊论文

  • 发表日期：

    2025年1月27日

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  • Shahrzad Shokati,
  • Saman Sargazi,
  • Mahdi Majidpour,
  • Shekoufeh Mirinejad,
  • Zari Naderi Ghale-Noie,
  • Mansour Shahraki,
  • Sara Sargazi,
  • Maryam Piri

摘要

This study is aimed to examine the association between three variants of the FMO3 gene—rs2266782G/A (E158K), rs2266780A/G (E308G), and rs1736557G/A (V257M)—and susceptibility to type 2 diabetes mellitus (T2DM), given the role of flavin-containing dimethylaniline monooxygenases (FMOs) in catalyzing trimethylamine N-oxide (TMAO), a compound linked to T2DM. A total of 800 adults were genotyped using PCR–RFLP or ARMS-PCR techniques, and various metabolic parameters, including lipid profiles and fasting blood sugar levels, were recorded for each participant. The findings revealed a significant association between the rs1736557 variant and T2DM under multiple inheritance models. Notably, the A allele of rs1736557 and the G allele of rs2266780 were associated with a decreased risk of T2DM, with risk reductions of 38% and 25%, respectively. Some genotype combinations exhibited a negative correlation with T2DM susceptibility, while certain haplotypes correlated with an increased risk of the disease. Bioinformatics analyses indicated that these genetic variants did not alter the secondary structure of FMO3 mRNA. Ultimately, the study identified significant associations between specific FMO3 variations and T2DM risk, emphasizing the need for further research with diverse populations to validate these findings.

Graphical Abstract