The-514c>T Polymorphism In Thelipcgene Modifies Type 2 Diabetes Risk Through Modulation Of Hdl-Cholesterol Levels In Mexicans

Purpose Both type 2 diabetes (T2D) and low levels of high-density lipoprotein cholesterol (HDL-C) are very prevalent conditions among Mexicans. Genetic variants in theLIPCgene have been associated with both conditions. This study aimed to evaluate the association of the -514C < T (rs1800588)LIPCgene polymorphism with different metabolic traits, particularly the effects of this polymorphism on HDL-C plasma levels and T2D risk. Methods Mediation analysis was used to assess the direct and indirect effects of the -514C>TLIPCgene variant on HDL-C levels, T2D risk, and body mass index (BMI), in 2105 Mexican mestizo participants. We also assessed the functional effect of the -514C>TLIPCvariant on the promoter activity of a reporter gene in the HepG2 cell line. Results Direct effects show that the -514C>TLIPCpolymorphism is significantly associated with increased HDL-C plasma levels (beta = 0.03;p < 0.001). The -514C>T variant resulted in an indirect protective effect on T2D risk through increasing HDL-C levels (beta = - 0.03;p < 0.001). Marginal direct association between -514C>T and T2D was found (beta = 0.08;p = 0.06). Variables directly influencing T2D status were European ethnicity (beta = - 7.20;p < 0.001), age (beta = 0.04;p < 0.001), gender (beta = - 0.15;p = 0.017) and HDL-C (beta = - 1.07;p < 0.001). In addition, we found that the -514C>T variant decreases the activity ofLIPCpromoter by 90% (p < 0.001). Conclusions The -514C>T polymorphism was not directly associated with T2D risk. HDL-C acts as a mediator between -514C>TLIPCgene variant and T2D risk in the Mexican population.