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Background <p>Type 2 diabetes mellitus (T2DM) is a significant global health burden due to rising incidence, cardiovascular complications, and multifactorial etiology involving genetic and environmental factors. One of the most common SNPs (single-nucleotide polymorphisms) is rs12255372 within the <i>TCF7L2</i> gene, which has been shown to have a substantial impact on the risk of developing T2D.&#xa0;&#xa0;</p> Objective <p>The purpose of this study was to investigate the relationship between the polymorphism rs12255372 of the <i>TCF7L2</i> gene and T2DM in the Middle Euphrates region of Iraq.</p> Methods <p>The study consisted of 300 individuals, comprising 150 T2DM patients and 150 healthy age and sex matched controls. Biochemical parameters (FBS, HbA1c, lipid profile, insulin) and genetic data were obtained from blood samples. Genotyping for the rs12255372 polymorphism was performed using the PCR-TETRA ARM method. Statistical analysis conducted included Hardy–Weinberg Equilibrium, logistic regression, multivariate analysis of covariance (MANCOVA), and Bayesian statistics, which were applied to validate genotype-metabolic trait associations and support the robustness of observed findings.</p> Results <p>A considerable association was noted between rs12255372 and T2DM under all of the tested genetic models: codominant, dominant, recessive, and additive. Carriers of the T allele (both GT and TT genotypes) had a significantly greater risk of acquiring T2DM (adjusted OR for GT: 2.67, TT: 6.34; <i>p</i> &lt; 0.0001). T allele prevalence was markedly higher among diabetics, thus confirming its status as a potential genetic risk factor. The polymorphism was also associated with worsening glycemic control, exacerbated dyslipidemia, and higher insulin resistance. MANCOVA confirmed that rs12255372 genotypes significantly influenced metabolic trait variation.</p> Conclusion <p>The polymorphism rs12255372 within the <i>TCF7L2</i> gene is strongly associated with T2DM predisposition and adverse metabolic traits among Middle Euphrates residents. This SNP may serve as a genetic risk marker for T2DM and contribute to risk stratification efforts. Its identification could support early intervention strategies when integrated with other genetic and lifestyle factors.</p>

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The TCF7L2 rs12255372 variant as a predictor of type 2 diabetes susceptibility in the Iraqi Middle Euphrates region

  • 期刊论文

  • 发表日期：

    2025年9月4日

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  • Hind Abdul Hussain,
  • Ahmed Naseer Kaftan

摘要

Background

Type 2 diabetes mellitus (T2DM) is a significant global health burden due to rising incidence, cardiovascular complications, and multifactorial etiology involving genetic and environmental factors. One of the most common SNPs (single-nucleotide polymorphisms) is rs12255372 within the TCF7L2 gene, which has been shown to have a substantial impact on the risk of developing T2D.  

Objective

The purpose of this study was to investigate the relationship between the polymorphism rs12255372 of the TCF7L2 gene and T2DM in the Middle Euphrates region of Iraq.

Methods

The study consisted of 300 individuals, comprising 150 T2DM patients and 150 healthy age and sex matched controls. Biochemical parameters (FBS, HbA1c, lipid profile, insulin) and genetic data were obtained from blood samples. Genotyping for the rs12255372 polymorphism was performed using the PCR-TETRA ARM method. Statistical analysis conducted included Hardy–Weinberg Equilibrium, logistic regression, multivariate analysis of covariance (MANCOVA), and Bayesian statistics, which were applied to validate genotype-metabolic trait associations and support the robustness of observed findings.

Results

A considerable association was noted between rs12255372 and T2DM under all of the tested genetic models: codominant, dominant, recessive, and additive. Carriers of the T allele (both GT and TT genotypes) had a significantly greater risk of acquiring T2DM (adjusted OR for GT: 2.67, TT: 6.34; p < 0.0001). T allele prevalence was markedly higher among diabetics, thus confirming its status as a potential genetic risk factor. The polymorphism was also associated with worsening glycemic control, exacerbated dyslipidemia, and higher insulin resistance. MANCOVA confirmed that rs12255372 genotypes significantly influenced metabolic trait variation.

Conclusion

The polymorphism rs12255372 within the TCF7L2 gene is strongly associated with T2DM predisposition and adverse metabolic traits among Middle Euphrates residents. This SNP may serve as a genetic risk marker for T2DM and contribute to risk stratification efforts. Its identification could support early intervention strategies when integrated with other genetic and lifestyle factors.