Diabetes Mellitus influence in Lipoprotein(a) gene expression and association to coronary artery disease

Abstract Introduction Lp(a) and type 2 diabetes mellitus are both known and established risk factors for the development of coronary artery disease (CAD). Lp(a) levels are 75% to 95% heritable and predominately determined by single-nucleotide variants at the LPA gene; rs3798220 is one of the most studied variants and accounts for a significant portion of Lp(a) levels. Whether diabetes could influence the LPA rs3798220 account for Lp(a) levels is unknown. Aim Evaluate whether there is a different association between polymorphism LPA rs3798220 T>C and Lp(a) levels and their association with CAD in diabetic and non-diabetic populations. Methods 3,209 subjects (mean age 59.3±8.9 years, 76.3% male were selected from the data set of the Research Center. The LPA rs3798220 T>C was genotyped with the TaqMan PCR assay (Applied Biosystems 7300 Real-Time). This genetic variant has a minor allele frequency (MAF) <2%; hence, the risk homozygous CC is a rare genotype, and we used the heterozygous CT in our analysis. Lp(a) biochemical levels were measured in all participants. From the 3,209 participants, 810 had diabetes, and 2399 were no diabetics. For each group, chi-squared tests were used to determine the association of CAD prevalence by genotype, and t-tests were used to evaluate differences in CAD prevalence by Lp(a) levels. Results In non-diabetic subjects, LPA TC was significantly associated with CAD in non-diabetic subjects compared with TT (p<0.0001). Similarly, Lp(a) was higher in the CAD population (37.2±39.7) compared to the healthy population (25.6±30.0) (p<0.0001). In diabetic group, Lp(a) was higher in the CAD population (38.5±41.4) compared to the population without CAD (23.9±29.2) (p<0.0001). Nevertheless, there was no difference in genotype between CAD and non-CAD patients (p=0.710). Conclusion The LPA rs3798220 T>C variant in non-diabetic group can explain high Lp(a) levels and their association with CAD. However, in patients with diabetes, Lp(a) is elevated in CAD patients besides the fact that no significant genotype differences were displayed. Non-genetic influences like behavioural factors or even epigenetic changes may probably explain high Lp(a) levels in this population.