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.
Highlights
Coronary artery disease (CAD) is the leading cause of mortality and morbidity in many countries including China [1,2]
There are no significant difference for sex and mean body mass index (BMI), family history of CAD, previous smoker, hypertension, hyperlipidemia, diabetes mellitus, mean ejection fraction, circumflex branch of left coronary artery system, right coronary artery system, off-pump coronary artery bypass grafting (OPCAB) or conventional coronary artery bypass grafting for Left main coronary artery disease (LMCAD) patients and more peripheral coronary artery disease (MPCAD) patients (Table 1)
When the IL-6R rs7529229 TT homozygote genotype was used as the reference group, the CC genotype was associated with the increased risk for LMCAD (CC vs. TT, adjusted odds ratios (ORs) = 1.46, 95% confidence intervals (CIs) = 1.02–2.11, p = 0.042)
Summary
Coronary artery disease (CAD) is the leading cause of mortality and morbidity in many countries including China [1,2]. Left main coronary artery disease (LMCAD) is a particular severe phenotype of CAD because it is associated with higher risk of fatal cardiovascular events [3]. More investigations are needed in detecting association between genetic variants and CAD phenotype. Interleukin (IL) plays a key role in the inflammatory response, immune regulation and development of CAD. Of the biological and pathologic significance of IL, we performed a genetic association study on the SNPs of IL-1A, IL-1B, IL-6, IL-6R, IL-8 and IL-10. The objective of this investigation was to evaluate the association between IL SNPs and LMCAD susceptibility compare with MPCAD in a hospital-based case-only study.
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