Abstract

AimsTo investigate the association of several single nucleotide polymorphisms (SNPs) within Interleukin-6 (IL- 6) and vitamin D receptor (VDR) gene, and additional gene- gene and gene- smoking interaction with coronary heart disease (CHD) risk in a Chinese population.MethodsHardy-Weinberg equilibrium (HWE) examination was used by SNPstats (http://bioinfo.iconcologia.net/SNPstats). Generalized multifactor dimensionality reduction (GMDR) was used to screen the best interaction combination among SNPs and smoking. Stratified analysis for gene- smoking interaction was investigated by logistic regression.ResultsCHD risk was significantly higher in carriers with the C allele of rs1800796 within IL-6 gene than those with GG genotype (GC+ CC versus GG), adjusted OR (95%CI) =1.62 (1.19-2.23); CHD risk was also higher in carriers with the T allele of rs2228570 within VDR gene than those with CC genotype (CT+ TT versus CC), adjusted OR (95%CI) = 1.68 (1.26-2.17). However, we did not find any direct associations of the others SNPs in IL- 6 and VDR gene with CHD risk. We also found a significant interaction between rs1800796 and smoking, the cross-validation consistency of this two- locus model was 10/ 10, and the testing accuracy was 60.11%. Current smokers with rs1800796- GC or CC genotype have the highest CHD risk, compared to never- smokers with rs1800796- GG genotype within IL- 6 gene, OR (95%CI) = 2.57 (1.74 -3.46).ConclusionsWe found that the C allele of rs1800796 within IL-6 and T allele of rs2228570 within VDR gene, interaction between rs1800796 and smoking were all associated with increased CHD risk.

Highlights

  • Coronary heart disease (CHD) is a major cause of death and disability worldwide [1]

  • CHD risk was significantly higher in carriers with the C allele of rs1800796 within IL-6 gene than those with GG genotype (GC+ CC versus GG), adjusted OR (95%CI) =1.62 (1.19-2.23); CHD risk was higher in carriers with the T allele of rs2228570 within vitamin D receptor (VDR) gene than those with CC genotype (CT+ TT versus CC), adjusted OR (95%CI) = 1.68 (1.26-2.17)

  • We did not find any direct associations of the others single nucleotide polymorphisms (SNPs) in IL- 6 and VDR gene with CHD risk

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Summary

Introduction

Coronary heart disease (CHD) is a major cause of death and disability worldwide [1]. In China, the CHD death rate increased from 141 per 10,000,000 person-years in 2003 to 229 per 10,000,000 person-years in 2010 [2, 3]. CHD is associated with inflammation and considered as complex chronic diseases relating to multiple genes. Among these inflammatory cytokines, IL-6 is a circulating cytokine known as a regulation for inflammatory reaction, accelerates bone resorption [5] and plays a key role in atherogenesis and thrombosis [6, 7]. The IL-6 gene is mapped to chromosome 7 at p21 [8]

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