白细胞介素-35 基因多态性与中国汉族人群冠心病易感性相关因素的交互作用分析。
Analysis for interaction between interleukin-35 genes polymorphisms and risk factors on susceptibility to coronary heart disease in the Chinese Han population.
机构信息
Deputy Chief Physician, Director of Cardiovascular Department of the First Naval Hospital of Southern Theater Command, PLA, Haibin Avenue 10, Zhanjiang, 524005, Guangdong Province, People's Republic of China.
Out Patient Department of the First Naval Hospital of Southern Theater Command, PLA, Zhanjiang, 524005, People's Republic of China.
出版信息
BMC Cardiovasc Disord. 2021 Jan 6;21(1):6. doi: 10.1186/s12872-020-01811-8.
BACKGROUND
The relationship between IL-35 genes polymorphism and susceptibility to coronary heart disease has not been tested in the largest Han population in China. The aim of this study was to explore the effect of single nucleotide polymorphisms (SNPs) of interleukin-35 (IL-35) genes and its relationship with environment on the risk of coronary heart disease (CHD).
METHODS
We performed Hardy-Weinberg equilibrium test on the control group. The relationship between the four SNPs of IL-35 genes and the risk of coronary heart disease was studied by multivariate logistic regression. The best interaction was identified with generalized multifactor dimensionality reduction (GMDR). Logistic regression was used for investigation on association between four SNPs and CHD risk.
RESULTS
Logistic regression analysis showed that the C allele of rs428253 and the G allele of rs2243115 were independently correlated with increased risk of CHD, and adjusted ORs (95% CI) were 1.91 (1.28-2.64) and 1.80 (1.30-2.23), respectively. However, there was no significant association between CHD and rs4740 or rs568408. GMDR model indicated a best model for CHD risk consisted of rs428253 and current smoking, which scored 10/10 for both the sign test and cross-validation consistency (p = 0.010). Therefore, this overall multi-dimensional model had the highest cross-validation consistency, regardless of how the data were divided. This provided an evidence of gene-environment interaction effects. We also found that current smokers with rs428253-GC/CC genotype have the highest CHD risk, compared to never smokers with rs428253-GG genotype, OR (95% CI) = 3.04 (1.71-4.41), after adjustment for age, gender, hypertension, T2DM and alcohol consumption status.
CONCLUSIONS
In this study, the C allele of rs428253 and the G allele of rs2243115, and the interaction rs428253 and current smoking were correlated with increased risk of CHD.
背景
白细胞介素-35（IL-35）基因多态性与冠心病易感性的关系尚未在我国最大的汉族人群中进行测试。本研究旨在探讨白细胞介素-35（IL-35）基因单核苷酸多态性（SNP）及其与环境的相互作用对冠心病（CHD）发病风险的影响。
方法
我们对对照组进行了 Hardy-Weinberg 平衡检验。采用多元 logistic 回归分析 IL-35 基因四个 SNP 与冠心病发病风险的关系。采用广义多因子降维法（GMDR）确定最佳相互作用。采用 logistic 回归分析四个 SNP 与 CHD 发病风险的关联。
结果
Logistic 回归分析显示，rs428253 的 C 等位基因和 rs2243115 的 G 等位基因与 CHD 发病风险增加独立相关，调整后的 OR（95%CI）分别为 1.91（1.28-2.64）和 1.80（1.30-2.23）。然而，rs4740 或 rs568408 与 CHD 无显著相关性。GMDR 模型显示，一个最佳的 CHD 风险模型由 rs428253 和当前吸烟组成，其符号检验和交叉验证一致性得分为 10/10（p=0.010）。因此，无论数据如何划分，这个整体多维模型的交叉验证一致性最高，提供了基因-环境相互作用效应的证据。我们还发现，与从不吸烟者 rs428253-GG 基因型相比，携带 rs428253-GC/CC 基因型且当前吸烟的吸烟者患 CHD 的风险最高，调整年龄、性别、高血压、T2DM 和饮酒状态后，OR（95%CI）为 3.04（1.71-4.41）。
结论
在这项研究中，rs428253 的 C 等位基因和 rs2243115 的 G 等位基因以及 rs428253 与当前吸烟的相互作用与 CHD 发病风险增加相关。
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