C5L2 Gene Polymorphisms and Their Interaction with Metabolic and Inflammatory Pathways in T2DM-Associated Coronary Heart Disease: Insights from an Integrative Genetic and Clinical Analysis

Abstract

This study investigates the role of C5L2 gene polymorphisms and their interaction with metabolic and inflammatory factors in the development of coronary heart disease (CHD) among individuals with type 2 diabetes mellitus (T2DM) in a Chinese population from Xinjiang. The C5L2 gene encodes a receptor involved in lipid metabolism, immune regulation, and inflammatory signaling. A total of 951 participants were recruited in a hospital-based case-control study, including 206 patients with comorbid T2DM and CHD and 745 age- and sex-matched healthy controls. Clinical and biochemical parameters were measured using standardized laboratory procedures. Two single-nucleotide polymorphisms (rs2972607 and rs8112962) in the C5L2 gene were genotyped using the improved multiplex ligation detection reaction method. Statistical analyses were conducted to evaluate associations between genotypes, clinical traits, and disease risk, and multifactor dimensionality reduction analysis was used to explore gene-environment interactions. Individuals in the case group showed significantly higher levels of glucose, triglyceride-glucose index, white blood cells, lactate dehydrogenase, and creatine kinase compared to controls. The rs2972607 variant was independently associated with increased risk of T2DM-associated CHD and was significantly correlated with HDL cholesterol, platelet indices, and liver function markers. Interaction analyses revealed complex gene-environment networks, with glucose and the TyG index emerging as central predictors. The rs2972607 polymorphism appeared to modulate the strength of these interactions, suggesting a mechanistic role in disease susceptibility. These findings highlight the value of integrative genetic and clinical analyses for improving risk stratification and support the potential utility of C5L2 genotyping in personalized prevention strategies for cardiometabolic disease.