Gene expression and six single nucleotide polymorphisms of interleukin-6 in rheumatoid arthritis: A case-control study in Iraqi patients

Abstract

Background: Interleukin-6 (IL-6) plays a significant role in pathogenesis of rheumatoid arthritis (RA), but its single nucleotide polymorphisms (SNPs), as well as therapy may modulate such role.

Objectives: It was aimed to determine gene expression and six SNPs (rs1800796 C/G, rs7802307 A/C/T, rs7802308 A/T, rs36215814 A/G, rs184229712 A/G and rs867254801 C/G) of IL6 in etanercept-treated Iraqi Arab RA patients.

Materials and methods: Fifty-one RA patients and 45 controls were enrolled, and the determinations were carried out by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Sanger’s DNA sequencing. Disease activity and laboratory markers were considered in these evaluations, which were the first presentation in Iraqi patients.

Results: The △Ct mean of IL6 mRNA showed a significant increase in RA patients compared to control (9.084 ± 0.964 vs. 6.780 ± 2.240; p = 0.0001). In terms of a relative expression, the 2^-△△Ct means showed no significant variations between subgroups of patients distributed by clinical and laboratory findings, with the exception of C-reactive protein (CRP). CRP-positive patients showed a lower mean compared to CRP-negative patients (0.201 ± 0.109 vs. 0.312 ± 0.131; p = 0.001). Distributing patients by gender and duration of disease also revealed significant variations between male and female patients. With respect to SNPs, allele and genotype frequencies of four SNPs (rs1800796, rs7802307, rs184229712 and rs867254801) showed variations between patients and controls, while no differences were reported for rs7802308 and rs36215814 SNPs. In addition, IL6 gene expression was significantly influenced by two SNP genotypes (rs36215814 GA and rs184229712 AG) compared to the corresponding GG genotypes.

Conclusion: Gene expression of IL6 was down-regulated in RA patients, especially CRP-negative patients. Moreover, four SNPs of such cytokine may have a role in RA risk.

Keywords: Rheumatoid arthritis, Interleukin-6, Single nucleotide polymorphism, Gene expression, Etanercept