Interleukin‐18‐promoter polymorphisms are not relevant in rheumatoid arthritis

Abstract

Interleukin-18 (IL-18), a member of the IL-1 family, is known to play a relevant role in rheumatoid arthritis (RA) physiopathology mainly by promoting the inflammatory response. The aim of this work was to investigate the possible implication of two single-nucleotide polymorphisms (SNPs) [-607 A/C (rs1946518) and -137 G/C (rs187238)] within the IL-18-promoter region in RA predisposition and clinical course. A total of 362 unrelated RA patients and 339 healthy controls were genotyped using a real-time polymerase chain reaction (PCR) method for the -607 A/C SNP and a sequence-specific PCR method (PCR-SSP) for the -137 G/C polymorphism. No statistically significant differences were observed for both -607 and -137 IL-18-promoter polymorphisms between RA patients and controls, considering either allelic or genotypic frequencies. In addition, no association was found with the haplotypes inferred by the two polymorphisms and RA susceptibility. This was also the case when RA patients were stratified according to sex, age at the onset of the disease, rheumatoid factor status, and extraarticular manifestations. Our data suggest that -607 A/C (rs1946518) and -137 G/C (rs187238) polymorphisms within the IL-18-promoter region do not play a major role in RA predisposition.

Genetic Polymorphism of Interleukin-18 Gene Promoter Region in Rheumatoid Arthritis Patients from Southern India

“…The allelic or genotypic frequencies seen at position -137 between subjects were also insignificant. Rueda et al, [23] and Pawlik et al, [24] reported that, IL-18-137 and -607 promoter polymorphisms were not significant with respect to RA courses and severities. Pan et al, [25] reported that IL-18 gene promoter -607 A/C polymorphism was not associated with development of autoimmune diseases.…”

Interleukin 18 gene promoter polymorphisms in Latvian patients with rheumatoid arthritis

“…Sivalingam et al (2003) found that controls had significantly higher frequency of the AA genotype at position -607 when compared to RA patients and concluded that the AA genotype at position -607 is associated with a protective effect against development of RA in Chinese individuals. Rueda et al (2005) observed no statistically significant differences between RA patients and controls in allelic and genotypic frequencies of -607C/A and -137C/G IL-18 promoter polymorphisms. In addition, no association was found with the haplotypes inferred by the two polymorphisms and RA susceptibility.…”

Association of IL-18 polymorphisms with rheumatoid arthritis: a meta-analysis

“…Thirteen studies were population-based and one was unclear. The genotype distributions in the controls for all studies were consistent with the Hardy-Weinberg equilibrium (Norton and Neel, 1965), except for three studies (Sivalingam et al, 2003;Rueda et al, 2005;Gurram et al, 2014). The characteristics of all included studies are summarized in Table 1.…”

“…The full texts of the remaining 19 records were carefully reviewed. Finally, 14 articles were included in the present meta-analysis (Sivalingam et al, 2003;Gracie et al, 2005;Rueda et al, 2005;Pawlik et al, 2006;Lee et al, 2007;Huang et al, 2007;Pawlik et al, 2009;Shi et al, 2011;Sugiura et al, 2011;Ying et al, 2011;Hashaad et al, 2012;Song et al, 2012;Farias et al, 2013;Gurram et al, 2014). All of the 14 articles were published between 2003 and 2014.…”