Interleukin-6 Receptor rs7529229 T/C Polymorphism Is Associated with Left Main Coronary Artery Disease Phenotype in a Chinese Population

Abstract

Left main coronary artery disease (LMCAD) is a particular severe phenotype of coronary artery disease (CAD) and heritability. Interleukin (IL) may play important roles in the pathogenesis of CAD. Although several single nucleotide polymorphisms (SNPs) identified in IL related genes have been evaluated for their roles in inflammatory diseases and CAD predisposition, the investigations between genetic variants and CAD phenotype are limited. We hypothesized that some of these gene SNPs may contribute to LMCAD phenotype susceptibility compared with more peripheral coronary artery disease (MPCAD). In a hospital-based case-only study, we studied IL-1A rs1800587 C/T, IL-1B rs16944 G/A, IL-6 rs1800796 C/G, IL-6R rs7529229 T/C, IL-8 rs4073 T/A, IL-10 rs1800872 A/C, and IL-10 rs1800896 A/G SNPs in 402 LMCAD patients and 804 MPCAD patients in a Chinese population. Genotyping was done using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and ligation detection reaction (LDR) method. When the IL-6R rs7529229 TT homozygote genotype was used as the reference group, the CC or TC/CC genotypes were associated with the increased risk for LMCAD (CC vs. TT, adjusted odds ratio(OR) = 1.46, 95% confidence interval (CI) = 1.02–2.11, p = 0.042; CC + TC vs. TT, adjusted OR = 1.31, 95% CI = 1.02–1.69, p = 0.037). None of the other six SNPs achieved any significant differences between LMCAD and MPCAD. The present study suggests that IL-6R rs7529229 T/C functional SNP may contribute to the risk of LMCAD in a Chinese population. However, our results were limited. Validation by a larger study from a more diverse ethnic population is needed.

Association of interleukin gene polymorphisms with the risk of coronary artery disease

“…Yu et al (2012) conducted a study in a Korean population, and reported that the IL-10 -592C/A and -819C/T gene polymorphisms might be associated with ischemic heart disease. However, in one study in a Chinese population, it was reported that IL-10 gene polymorphism was not correlated with the risk of CAD (He et al, 2014). In contrast, in a recent meta-analysis of 14 case-control studies with a total of 5006 patients and 3968 controls, it was reported that the IL-10 -1082 gene polymorphism might be associated with an increased overall risk of CAD, especially in Caucasians (Wang et al, 2012).…”

“…Several previous studies have reported the association between IL-10 gene polymorphisms and CAD risk, but these results have also been controversial Jin et al, 2013;Elsaid et al, 2014;He et al, 2014). Elsaid et al (2014) conducted a case-control study in an Indian population, and reported that the C allele of IL-6 -174G/C (rs1800795) and the G allele of IL-10 -1082A/G (rs1800896) were associated with an increased risk of CAD.…”

IL-6-174G/C and IL-6-572C/G polymorphisms are associated with increased risk of coronary artery disease

“…One animal experimental study has shown that several cytokines play a key role in the development of CAD (Kleemann et al, 2008). Several previous epidemiology studies have shown that polymorphisms in several cytokines, including interleukin-6 (IL-6), , are involved in the pathogenesis of CAD (Zhang et al, 2011;Huang et al, 2013;Opstad et al, 2011Opstad et al, , 2013Galimudi et al, 2014;He et al, 2014;Zhang et al, 2014). However, the results of these studies are inconsistent.…”

“…Many epidemiologic studies have observed that polymorphisms in the genes encoding interleukin-1 receptor antagonist, such as , are associated with the development of CAD (Zhang et al, 2011;Huang et al, 2013;Opstad et al, 2011Opstad et al, , 2013Galimudi et al, 2014;He et al, 2014;Zhang et al, 2014).…”

IL-8 -251A/T polymorphism contributes to coronary artery disease susceptibility in a Chinese population

“…Previous studies have demonstrated that sequence variations in this gene are associated with CAD, but their results have been inconsistent (Vogiatzi et al, 2008;He et al, 2014;Ren and She, 2015;Yang et al, 2015). Vogiatzi et al (2008) conducted an investigation into the influence of common IL-8 polymorphisms on CAD risk, showing a combination of the -251A/ T and -781C/T variants to be associated with susceptibility to this disease.…”