Exploring the Association between Genetic variant rs5925 in LDLR Gene and the Incidence of T2DM with CAD in Iraqi Population. A case-control Study

Abstract

Abstract Background The crucial function of the low-density lipoprotein receptor (LDLR) is to regulate cellular cholesterol levels. Changes in the LDLR gene can result in a notable rise in LDL cholesterol in the blood, potentially increasing the likelihood of T2DM with CAD, which involves atherosclerosis and coronary heart problems. Additionally, it impacts lipid levels in the bloodstream among Iraq's population. This study primarily aimed to explore the possible link between the LDLR rs5925 variation and cardiovascular disease (CVD) in individuals with type 2 diabetes in Iraqi population. Method The research involved a sample of 400 participants, categorized into two groups: 200 individuals with both Type 2 Diabetes Mellitus (T2DM) and coronary artery disease, and 200 healthy individuals without these medical conditions. The main objective of the investigation was to explore the potential link between a specific variation in the LDLR gene known as rs5925 and the susceptibility to these ailments. To achieve this, a logistic regression analysis was conducted to determine odds ratios (OR) and their corresponding 95% confidence intervals (CI). In this instance a case-control study employed the Allele Discrimination/SNP's Real-Time PCR TaqMan technique, utilizing the Mx3005P QPCR System to genotype the polymorphism. Result In the analysis of the frequencies of the LDLR gene polymorphism, rs5925 T/C, using the co-dominant model, it was observed that individuals affected by both Type 2 Diabetes (T2DM) and coronary artery disease (CAD) showed a notable increase in heterozygous genotype (TC) compared to the control group (adjusted odds ratio [OR] = 3.2, 95% confidence interval [CI] = 2.03–4.9, p < 0.0001). Additionally, it is worth noting that the homozygous recessive genotype (CC) also demonstrated a significant increase when compared to the control group (OR = 10.5, CI 95% = 2.6–6.1, p < 0.01). These findings suggest that individuals with the genotypes (TC) may be three times higher risk of developing Type 2 Diabetes (T2DM) along with coronary artery disease (CAD) compared to those with the wild type genotype (TT) as well as (CC) may be at nearly ten times. Conclusions This study is the inaugural instance of showing a link between the LDLR gene polymorphism and a heightened vulnerability to cardiovascular disease among patients with type 2 diabetes. The results of our study indicate an association between the variation in the LDLR gene rs5925 and the occurrence of both T2DM and CAD, also impacting lipid profiles.