Interleukin 4 and STAT6 gene polymorphisms are associated with systemic lupus erythematosus in Chinese patients
| Autor: | Wei J. Chen, Yao-Hsu Yang, Lin Yc, Pi-Hua Liu, Hsin-Hui Yu, Li-Chieh Wang, Jyh-Hong Lee, Bor-Luen Chiang |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Male
Risk China Genotype Single-nucleotide polymorphism Polymorphism Single Nucleotide Asian People Gene Frequency Rheumatology immune system diseases Humans Lupus Erythematosus Systemic Medicine Genetic Predisposition to Disease skin and connective tissue diseases Alleles Interleukin 4 STAT6 business.industry Haplotype Odds ratio Interleukin 10 Logistic Models Immunology Female Interleukin 18 Interleukin-4 Gene polymorphism STAT6 Transcription Factor business |
| Zdroj: | Lupus. 19:1219-1228 |
| ISSN: | 1477-0962 0961-2033 |
| Popis: | An imbalance between T Helper 1 (TH1) and T Helper 2 (TH2) cytokine production is important for the pathogenesis of systemic lupus erythematosus (SLE). We aimed to investigate gene—gene associations of TH1 and TH2 cytokines genes in Chinese patients with SLE. Twenty single nucleotide polymorphisms (SNPs) in eight cytokines genes were genotyped in 110 SLE patients and 138 healthy controls in a case—control association study. The minor allelic frequencies of interleukin4(IL4) -590 T/C, -33 T/C, 9241C/G, and IL10 -592 A/C were significantly increased in SLE patients compared with those in controls (p < 0.05). None of the separate 20 SNPs showed significant association with SLE after Bonferroni correction. An IL4 haplotype -590C/-33C/9241G/14965C was significantly associated with SLE (odds ratio 3.7, 95% confidence interval [CI] 1.5—8.9, p = 0.004, Bonferroni-corrected p = 0.024). A borderline significant three-locus gene—gene interaction among IL4 9241 C/G, IL4 -33 T/C, signal transducer and activator of transcription 6, IL4-induced (STAT6) 2892 C/T was detected by a multifactor dimensionality reduction test (p = 0.051). However, the presence of two at-risk genotypes lead to increased risk of SLE for two-locus interaction using logistic regression method. The risk of SLE increased significantly when a subject has two at-risk genotypes for IL4 -590C and STAT6 2892C (odds ratio, 3.24, 95% CI 1.5—7.0, p = 0.003, Bonferroni-corrected p = 0.009), IL4 -33C and STAT6 2892C (odds ratio 3.06, 95% CI 1.4— 6.7, p = 0.005, Bonferroni-corrected p = 0.015), as well as IL4 9241G and STAT6 2892C (odds ratio 3.34, 95% CI 1.6—7.1, p = 0.002, Bonferroni-corrected p = 0.006). Further, plasma IL-4 concentrations were significantly lower in SLE patients than in healthy controls (1.59 + 3.53 versus 5.67 + 11.28 pg/ml, p = 0.042). These results indicated that IL4 and STAT6 genes might be involved in the etiology of SLE and potentially increased SLE risk through their interaction effect in Chinese patients. |
| Databáze: | OpenAIRE |
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