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 DCt 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 ÀDDCt 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.

Serum level and single-nucleotide polymorphisms of toll-like receptor-7 among urinary bladder cancer Iraqi patients

“…The isolated DNA was subjected to PCR amplification using designed forward (5′-GGTGAGAAAC CCTGCTATAAA-3′) and reverse (5′-CAAACATCTG CTCCTCCTC-3′) primers, which were employed to amplify intron 2 region of human chromosome X containing rs179018, rs179019, rs179020, and rs179021 SNPs (chrX:12866832+12867830). The PCR protocol and conditions were as previously described [12]. The amplified PCR fragments were subjected to Sanger's sequencing using ABI3730XL automated DNA sequencer (Macrogen Corporation-Korea).…”

Relevance of Interleukins 6 and 8 Single Nucleotide Polymorphisms in Prostate Cancer: A Multicenter Study

“…IL-6 and IL-8 were reported to be incriminated in the initiation and progression of prostate tumorigenesis, as IL-6 induces C-reactive protein (CRP) production [12]; promotes PCa cell survival, proliferation, invasion; enhances the progression of PCa to the castration-resistant state; and ® : reference group, OR: odds ratio, CI: confidence interval, UL: upper limit, LL: lower limit. OR 1 , p 1 : odds ratio and p value for comparing between cancer and control.…”

“…Different studies have examined the effect of IL-6 SNP and/or IL-8 SNP on diseases' risk, activity, and progression. Results showed marked ethnicity-associated disparities and diverse findings [12,[16][17][18][19][20][21][22][23]. For instance, a meta-analysis of European and Asian studies on IL-6 SNP and rheumatoid arthritis (RA) risk showed that IL-6 SNP was significantly associated with RA in Asian patients but not in the Caucasian population [20].…”

“…IL-6 and IL-8 were reported to be incriminated in the initiation and progression of prostate tumorigenesis, as IL-6 induces C-reactive protein (CRP) production [ 12 ]; promotes PCa cell survival, proliferation, invasion; enhances the progression of PCa to the castration-resistant state; and inhibits apoptosis [ 16 , 17 ]. At the same time, IL-8 was found to enhance androgen independence, tumor growth, angiogenesis, and chemoresistance [ 13 ].…”

“…Some cytokines were found to be involved in the etiopathogenesis of PCa by inducing growth, proliferation, and metastasis that occur during the course of the disease. Interleukin-6 (IL-6) is a pleiotropic cytokine that has multiple roles as induction and maintenance of inflammation, stimulation of adaptive immunity, and some autoimmune processes [ 11 , 12 ]. IL-8 is known to have a role in immune surveillance, recruitment, and degranulation of neutrophils, inflammation, and angiogenesis [ 13 ].…”