Interleukin 4 and STAT6 gene polymorphisms are associated with systemic lupus erythematosus in Chinese patients
Journal
Lupus
Journal Volume
19
Journal Issue
10
Pages
1219-1228
Date Issued
2010
Author(s)
Abstract
An imbalance between T Helper 1 (TH1) and T Helper 2 (T H2) 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. ? The Author(s), 2010.
SDGs
Other Subjects
cytokine; interleukin 4; STAT6 protein; adult; article; Chinese; controlled study; disease association; female; gene frequency; gene interaction; genetic association; genotype; haplotype; human; logistic regression analysis; major clinical study; male; priority journal; single nucleotide polymorphism; systemic lupus erythematosus; Th1 cell; Th2 cell; Alleles; Asian Continental Ancestry Group; China; Female; Gene Frequency; Genetic Predisposition to Disease; Genotype; Humans; Interleukin-4; Logistic Models; Lupus Erythematosus, Systemic; Male; Polymorphism, Single Nucleotide; Risk; STAT6 Transcription Factor
Type
journal article