Oncotarget

Research Papers:

Interactions between vitamin D receptor VDR gene and Interleukin6 gene and environment factors on coronary heart disease risk in a Chinese Han population

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Oncotarget. 2017; 8:78419-78428. https://doi.org/10.18632/oncotarget.19472

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Ma Jun1, Guan Xue-Qiang1, Li Jia1, Xue Yang-Jing1, Zheng Cheng1 and Jin Ge1

1The Department of Cardiology, 2nd Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China

Correspondence to:

Jin Ge, email: [email protected]

Keywords: coronary heart disease, Interleukin-6, vitamin D receptor, single nucleotide polymorphisms, smoking

Received: March 09, 2017    Accepted: June 12, 2017    Published: July 22, 2017

ABSTRACT

Aims: To 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.

Methods: Hardy-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.

Results: 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 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).

Conclusions: We 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.