Lin J, Peng Y, Zhou B, Dou Q, Li Y, Yang H, Zhang L, Rao L
Department of Cardiology, West China Hospital, Sichuan University, 610041, Chengdu, P.R. China.
Herz. 2015 May;40(3):534-41. doi: 10.1007/s00059-013-4039-0. Epub 2014 Jan 22.
Autoimmune abnormalities appear to be major predisposing factors for dilated cardiomyopathy (DCM). Interleukin-21 (IL-21) gene polymorphisms have been previously found to be associated with autoimmune diseases. This study aimed to assess the role of IL-21 in DCM in a Han Chinese population.
A total of 364 independent DCM patients and 384 unrelated healthy controls were recruited for this case-control association study. rs2055979 and rs12508721 were genotyped by PCR-RFLP. IL-21 plasma levels in samples from DCM and control individuals were evaluated by ELISA. The association between the SNPs and overall survival (OS) was evaluated by Kaplan-Meier analysis. Hazard ratios and 95 % confidence intervals (CIs) were assessed in a Cox regression analysis with adjustment for sex and age.
The T allele frequencies of both SNPs were higher in DCM patients than in controls (p < 0.001). The genotypic frequencies of rs2055979 G > T and rs12508721 C > T were associated with DCM in the codominant, dominant, and recessive models (p < 0.05). IL-21 plasma levels in patients were higher than those of the control subjects (p = 0.009). The TT genotypes of both SNPs were associated with significantly higher plasma levels (prs2055979 = 0.03, prs12508721 < 0.001). Kaplan-Meier analysis showed that the genotypic frequencies of both SNPs were associated with OS in the dominant and the recessive models (p < 0.001). The TT genotypes of both SNPs were associated with the worst OS (p < 0.001).
Our findings suggest that theIL-21 gene plays an important role in susceptibility to DCM as well as in the clinical outcome of this ailment in the Han Chinese population.
自身免疫异常似乎是扩张型心肌病（DCM）的主要易感因素。白细胞介素-21（IL-21）基因多态性先前已被发现与自身免疫性疾病有关。本研究旨在评估IL-21在中国汉族人群DCM中的作用。
本病例对照关联研究共纳入364例独立的DCM患者和384例无关的健康对照。通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）对rs2055979和rs12508721进行基因分型。采用酶联免疫吸附测定（ELISA）评估DCM患者和对照个体样本中IL-21的血浆水平。通过Kaplan-Meier分析评估单核苷酸多态性（SNP）与总生存期（OS）之间的关联。在对性别和年龄进行调整的Cox回归分析中评估风险比和95%置信区间（CI）。
两个SNP的T等位基因频率在DCM患者中均高于对照组（p < 0.001）。rs2055979 G > T和rs12508721 C > T的基因型频率在共显性、显性和隐性模型中均与DCM相关（p < 0.05）。患者的IL-21血浆水平高于对照受试者（p = 0.009）。两个SNP的TT基因型均与显著更高的血浆水平相关（prs2055979 = 0.03，prs12508721 < 0.001）。Kaplan-Meier分析表明，两个SNP的基因型频率在显性和隐性模型中均与OS相关（p < 0.001）。两个SNP的TT基因型均与最差的OS相关（p < 0.001）。
我们的研究结果表明，IL-21基因在中国汉族人群中对DCM的易感性以及该疾病的临床结局均起重要作用。
