Interaction between SELP genetic polymorphisms with inflammatory cytokine interleukin-6 (IL-6) gene variants on cardiovascular disease in Chinese Han population

The aim of the study is to investigate the impact of SELP and IL-6 genetic single-nucleotide polymorphisms (SNPs) and its gene-gene interaction on cardiovascular disease (CVD) risk based on Chinese population. A total of 1082 subjects (519 males, 563 females), with a mean age of 53.9 +/- 13.1 years, were selected, including 540 CVD patients and 542 normal control participants. Logistic regression model was used to examine the association between six SNPs and CVD risk. Odds ratio (OR) and 95% confident interval (95% CI) were calculated. Generalized multifactor dimensionality reduction (GMDR) was employed to analyze the gene-gene interaction. CVD risk was significantly higher in carriers with rs1800805-A allele than those with GG genotype (GA + AA vs. GG), adjusted OR (95% CI) = 1.69 (1.31-2.16), and CVD risk was also higher in carriers with rs6136-AC or CC genotype than those with AA genotype (AC + CC vs. AA), adjusted OR (95% CI) = 1.78 (1.28-2.26), and higher in carriers with rs1800796-GC or CC genotype than those with GG genotype (CC + GC vs. GG), adjusted OR (95% CI) = 1.67 (1.25-2.14). GMDR analysis suggested a significant two-locus model (p = 0.0010) involving rs1800805 and rs1800796. Overall, the cross-validation consistency of this model was 10/10, and the testing accuracy was 62.17%, and participants with rs1800805-GA or AA and rs1800796-GC or CC genotype have the highest CVD risk, compared to participants with rs1800805-GG and rs1800796-GG genotypes, and OR (95% CI) was 2.52 (1.81-2.66). Our results support an important association of rs1800805, rs6136 minor allele of SELP gene, rs1800796 within IL-6 gene, and additional interaction between rs1800805 and rs1800796 with increased risk of CVD.