Analysis of IL-17 gene polymorphisms in Chinese patients with dilated cardiomyopathy

Department of Cardiology, West China Hospital of Sichuan University, Chengdu 610041, P.R. China.
Human immunology (Impact Factor: 2.14). 01/2013; 74(5). DOI: 10.1016/j.humimm.2013.01.019
Source: PubMed


Cardiomyopathy is one of the major causes of sudden death and/or progressive heart failure. Dilated cardiomyopathy (DCM), comprising 60% of the cases of identified cardiomyopathy, is the most common form of heart muscle disease. Interleukin 17 (IL-17) is a proinflammatory cytokine that has been implicated in the pathogenesis of various diseases. To evaluate the influence of IL-17A and IL-17F gene polymorphisms on the risk of DCM, a case-control study was conducted in a Chinese Han population. The TaqMan® SNP Genotyping Assay was used to genotype the SNP rs2275913 of IL-17A and SNP rs763780 of IL-17F in 288 DCM patients and 421 ethnicity-matched controls. No significant difference in genotypic and allelic frequencies between DCM patients and control subjects was observed. However, Results of stratified analysis revealed that rs763780 was associated with male DCM patients in a dominant genetic model (p = 0.031, OR = 1.83, 95% CI = 1.04 - 3.22). Our results suggest that the tested two IL-17 SNPs, rs2275913 and rs763780, are not found to be associated with DCM in the Chinese population studied.

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  • J Lin · Y Peng · B Zhou · Q Dou · Y Li · H Yang · L Zhang · L Rao ·
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    ABSTRACT: 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.
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    ABSTRACT: The interleukin 17A (IL-17A) which is located on chromosome 6p and has been linked to chronic inflammation, is an important candidate gene conferring coal workers' pneumoconiosis (CWP). The purpose of this study was to investigate the genetic association between single nucleotide polymorphisms (SNPs) of IL-17A and CWP in a Chinese population. We conducted a case-control study to investigate the role of four common SNPs in the IL-17A gene, and evaluated the relationship between these four SNPs and dust-exposure year, tobacco smoking and stages of CWP. A total of 1391 subjects was enrolled in this study, including 694 subjects in control group and 697 in case group. TaqMan based qRT-PCRs were taken to genotype rs2275913, rs3748067, rs4711998, and rs8193036 within the IL-17A gene. Luciferase assays were used to determine the effects of rs8193036 C > T alleles on the expression of IL-17A. Unconditional logistic regression analysis showed that the genotypes of rs3748067 AA (adjusted OR = 0.43, 95 % CI = 0.23-0.83) and rs8193036 TT (adjusted OR = 0.59, 95 % CI = 0.40-0.86) were associated with a decreased risk of CWP, particularly among subgroups of smokers (adjusted OR =0.34, 95 % CI = 0.13-0.86 for rs3748076; adjusted OR = 0.41, 95 % CI = 0.23-0.71 for 8193036) and CWP cases with stage I (adjusted OR = 0.45, 95 % CI = 0.21-0.98 for rs3748076; adjusted OR = 0.46, 95 % CI = 0.28-0.74 for 8193036). Furthermore, the polymorphism of rs3748067 significantly reduced the CWP risk among cases with over 27 years of dust exposure (adjusted OR = 0.42, 95 % CI = 0.18-0.97). The luciferase assays in two cell lines showed that the rs8193036 C > T substitution could reduce the expression of IL-17A, which was consistent with the findings of our association study. The rs3748067 G > A and rs8193036 C > T polymorphisms decrease CWP risk. These findings could be helpful in identifying individuals at decreased risk for CWP and further studies are warranted to validate them.
    BMC Pulmonary Medicine 07/2015; 15(1):79. DOI:10.1186/s12890-015-0076-1 · 2.40 Impact Factor
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