The Impact of Functional Promoter Variants in Interleukin-18 on Susceptibility to Rheumatoid Arthritis in Iranian Population.

Background: Interleukin-18 (IL-18) is recognized for its pro-inflammatory properties and plays a central role in the progression of rheumatoid arthritis (RA). The specific single-nucleotide polymorphisms (SNPs), rs1946518 (-607C>A) and rs187238 (-137G>C), that are found in the IL-18 promoter region can potentially impact the expression of the IL-18 gene. This study aimed to investigate the correlation between these two polymorphisms and RA in the Iranian population.

Materials and methods: In this study, we conducted a case-control analysis with a total of 275 subjects consisting of 135 patients with RA and 140 controls. The high-resolution melting (HRM) method, performed through real-time polymerase chain reaction, was utilized for genotyping these polymorphisms.

Results: Regarding the rs1946518 polymorphism, the frequency of AA and CA genotypes and allele A was significantly greater in the control group compared to the RA group (AA vs CC; OR: 0.42; 95%CI [0.198-0.872], CA vs CC; OR: 0.57; 95%CI [0.324-1.001], A vs C; OR: 0.58; 95%CI [0.401-0.836] (P < 0.05). There was no statistically significant difference in the frequency of genotypes and allele frequencies between the control and patient groups in terms of the rs187238 polymorphism (P > 0.05). The level of both the C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) was notably elevated in the patient group with CC genotype in rs1946518 (P < 0.05).

Conclusion: In the rs1946518 polymorphism, the AA and AC genotypes and the A allele demonstrated protective effects in RA. Besides, the CC genotype was associated with some laboratory characteristics in the RA group.