CYP2D6 polymorphism rs1065852 significantly increases the risk of type 2 diabetes

Background Genetic variations within the cytochrome P450 (CYP) gene family are significant determinants of type 2 diabetes mellitus (T2DM) susceptibility. This study aimed to investigate the association between CYP2C8 and CYP2D6 gene variants and the risk of T2DM.Methods We conducted a case-control...

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Bibliographic Details
Main Authors: Huiyi Wei, Qingbin Zhao
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Annals of Medicine
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Online Access:https://www.tandfonline.com/doi/10.1080/07853890.2025.2470956
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Summary:Background Genetic variations within the cytochrome P450 (CYP) gene family are significant determinants of type 2 diabetes mellitus (T2DM) susceptibility. This study aimed to investigate the association between CYP2C8 and CYP2D6 gene variants and the risk of T2DM.Methods We conducted a case-control study involving 512 individuals with T2DM and 515 controls. Genotyping of CYP2C8 and CYP2D6 polymorphisms was performed using the Agena MassARRAY system. Logistic regression analysis was employed to estimate the odds ratios (ORs) and 95% confidence intervals (CIs), thereby assessing the relationship between these genetic variants and T2DM risk. Additionally, multifactor dimensionality reduction (MDR) was utilized to assess the potential interaction effects of SNPs on T2DM risk.Results The study found a strong correlation between rs1065852 and increased risk of T2DM in overall (A vs. G: OR = 1.22, 95% CI: 1.03–1.45, p = .024; AA vs. GG: OR = 1.46, 95% CI: 1.04–2.06, p = .031; AA–AG vs. GG: OR = 1.36, 95% CI: 1.04–1.79, p = .026; additive: OR = 1.21, 95% CI: 1.02–1.44, p = .027), males and age < 59 subgroups. However, there is no significant association between the CYP2C8 polymorphisms (rs1934953, rs1934951, rs2275620 and rs17110453) and T2DM risk. MDR analysis results showed that the best model was the one locus model (rs1065852, testing accuracy = 0.534; OR = 1.39; 95% CI: 1.05–1.85; p = .023; CVC = 10/10), indicating that rs1065852 is an independent risk factor for T2DM.Conclusions This study suggests that rs1065852 (CYP2D6) is an independent risk factor for T2DM. Further research is warranted to validate these results and explore their clinical implications.
ISSN:0785-3890
1365-2060