Association of interleukin-1 family cytokines single nucleotide polymorphisms with susceptibility to systemic sclerosis: an independent case–control study and a meta-analysis

Abstract

The aim of our study was to investigate the association of five single nucleotide polymorphisms in interleukin-1 (IL-1) gene with susceptibility to systemic sclerosis (SSc) in a Chinese population. A total of 58 SSc patients and 113 healthy controls were enrolled. TaqMan allele discrimination assay was performed to detect the genotyping of IL-1A -889C/T (rs1800587), IL-1B -511C/T (rs16944), IL-18 -607C/A (rs1946518), IL-18 -137G/C (rs187238) and IL-33 rs7044343. The association between these SNPs and SSc risk was analyzed. Furthermore, a meta-analysis of relevant studies on the association of IL-1A -889C/T (rs1800587) and IL-1B -511C/T (rs16944) with the susceptibility to SSc was performed. Through the genotyping, significant associations for SSc were found for: IL-1A -889C/T genotype frequencies (P = 0.000), dominant model (P = 0.000), recessive model (P = 0.001) and allele T frequency (P = 0.000). Among SSc patients, dyspnea was significantly associated with IL-18 -607C/A genotype frequency and IL-33 rs7044343 allele frequency (P = 0.037, P = 0.042, respectively). In addition, elevated erythrocyte sedimentation rate was significantly associated with IL-18 -137G/C (rs187238) genotype and allele frequency (P = 0.019, P = 0.006, respectively). While meta-analysis showed there was no significant association between IL-1A -889C/T polymorphism and SSc, for IL-1B -511C/T (rs16944), significant associations were found in the comparison of allele C versus T (OR 1.267, 95 % CI 1.016-1.580) by combined different outcomes. Results showed that IL-1A -889C/T (rs1800587) was associated with SSc susceptibility in the Chinese population. However, this association was not supported by a meta-analysis of all relevant studies. Further investigations are required to verify our findings.

The Roles of IL-1 Family Cytokines in the Pathogenesis of Systemic Sclerosis

“…The human IL-1α (IL-1A) gene contains common SNPs including rs1800587 and rs17561, which have been reported to be linked to several autoimmune diseases in some populations. IL-1A rs1800587 was reported to be associated with SSc susceptibility in the Slovak Caucasian, Japanese, and Chinese populations (13–15). However, this association was not supported by other relevant studies (16).…”

“…Results showed that IL-18 rs187238 and IL-18 rs1946518 polymorphism were not correlated with SSc susceptibility. However, ESR and dyspnea were associated with IL-18 rs187238 and IL-18 rs1946518 polymorphism, respectively (13).…”

Role of Alarmins in the Pathogenesis of Systemic Sclerosis

“…Genome-wide association studies have revealed associations between genes encoding IL-1 family cytokines and SSc. The human IL-1α (IL-1A) gene contains the sodium nitroprusside (SNP) rs1800587, which has been reported to be associated with SSc susceptibility in the Slovak Caucasian, Japanese, and Chinese populations [ 127 ]. However, in a very recent meta-analysis, IL-1A rs1800587 polymorphism seems not to be statistically linked to the risk of SSc [ 128 ].…”

Interleukin-33 in Systemic Sclerosis: Expression and Pathogenesis

“…Genetic polymorphisms in the IL-33 gene may be useful for the prediction of the risk of various diseases. The IL-33 rs7044343 CC genotype was suggested to be associated with an increased risk of developing SSc and a decreased risk of developing RA; the T allele may be a susceptibility marker for premature coronary artery disease and central obesity and possibly involved in the regulation of IL-33 production ( 53 , 75 – 77 ). The first monoclonal anti-ST2 antibody, CNTO-7160, was recently designed as a new IL-33 inhibitor; this antibody is being evaluated in phase I clinical trials for the treatment of severe asthma and atopic dermatitis, but no data have been published to date ( 78 ).…”