Association of CYP8B1 rs3732860 polymorphism and gene expression with oxidative stress and biochemical markers in Type 2 diabetes mellitus

Abstract

Background

Type 2 diabetes mellitus (T2DM) is a multifactorial metabolic disorder characterized by chronic hyperglycemia, oxidative stress, and low-grade inflammation. The CYP8B1 gene, a key regulator of bile acid synthesis and hepatic metabolism, may be influenced by oxidative status and has emerged as a potential contributor to T2DM pathogenesis. This study examined the association between CYP8B1 rs3732860 polymorphism, gene expression levels, and various biochemical and oxidative stress markers in individuals with T2DM.

Methods

A total of 198 subjects (132 T2DM patients and 66 healthy controls) were genotyped for the CYP8B1 rs3732860 variant. Biochemical parameters including HbA1c, glutathione peroxidase (GPX), catalase, malondialdehyde (MDA), superoxide dismutase (SOD), interleukin-10 (IL-10), interferon-gamma (IFN-γ), and nitric oxide (NO) were measured. CYP8B1 expression was assessed using qPCR (ΔCt values). Statistical analyses included logistic regression, chi-square, ANOVA, and ROC curve analysis.

Results

The TC genotype was significantly associated with increased T2DM risk (OR = 4.51, 95 % CI: 1.85–11.01, p = 0.001), while the CC genotype showed a non-significant trend (OR = 2.25, p = 0.078). CYP8B1 expression differed significantly among genotypes (p < 0.001), with highest expression in CC carriers. MDA levels also varied by genotype (p = 0.001), suggesting a link between oxidative stress and gene regulation. ROC analysis identified catalase (AUC = 0.909) and SOD (AUC = 0.764) as strong predictors of T2DM.

Conclusion

The CYP8B1 rs3732860 polymorphism is associated with altered gene expression and oxidative stress in T2DM, highlighting its potential role as a metabolic regulator and biomarker of disease susceptibility.