Abstract
Objective To explore the relationships between single nucleotide polymorphisms (SNP) in IL-6 gene promoter region and susceptibility to tuberculosis,and to investigate the influences of SNP on IL-6 production in various genotypes.Methods A case-control study was conducted on 495 patients with tuberculosis and 358 healthy controls.Sequenom MassARRAY system was used to detect genotypes of 6 SNPs (rs13306436,rs2069824,rs36215814,rs 1800797,rs1800796,and rs1800795) in IL-6 gene.Allelic frequency in cases and controls was compared using Chi-square test and odds ratio (OR) was calculated to clarify the association with risk for tuberculosis.CD14+ monocytes isolated from PBMCs of the subjects with MACS beads were stimulated with Mtb lysate and 19 × 103 lipoprotein.Then the concentrations ofIL-6 in supernatants of CD14+ monocytes with different genotypes were determined by ELISA.Results Genotype distribution of 6 SNPs in healthy controls was in accordance with Hardy-Weinberg equilibrium.G enotype frequencies of rs1800796 were 64.5% (CC),30.7% (CG),4.8% (GG) in TB group and 6.4%(CC),34.9% (CG),8.7% (GG) in control group,respectively.The allele frequency of G in TB group (21.3%) was lower than that in control group (26.1%) (P value =0.02),and allele C carriers were at higher risk for TB (OR 1.40,95% CI=1.11-1.75).There were no significant differences in allele frequencies for other SNPs.With 19×103 lipoprotein stimulation,the concentration of IL-6 in CD14+ monocytes isolated from individuals with rs1800796 GG genotype was significantly less than those with CC or CG genotype.However,there was no difference observed among different genotypes with Mycobacterium tuberculosis (Mtb)stimulation.Conclusion This is the first report showing that IL-6 gene rs1800796 polymorphism with C as the susceptible allele was associated with the susceptibility to tuberculosis in Han nationality.Moreover,as a functional SNP,rs1800796 polymorphism could affect IL-6 production. Key words: Interleukin-6; Single nucleotide polymorphism; Tuberculosis; Susceptibility; Protein expression
Published Version
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