Systemic lupus erythematosus and genetic variation in the interleukin 1 gene cluster: a population based study in the southeastern United States

Abstract

Background: Interleukin (IL)1a and IL1b, and their endogenous receptor antagonist (IL1Ra), have been related to the pathology of systemic lupus erythematosus (SLE), but the role of IL1 polymorphisms in the aetiology of SLE is unknown. Objective: To examine polymorphisms at IL1a 2889(CRT), IL1a +4845(CRT), IL1b 2511(CRT), IL1b +3953(GRT), and IL1Ra (86 bp VNTR) in a population based study of SLE in North Carolina and South Carolina. Methods: Genotypes from 230 cases who met ACR classification criteria, and from 275 controls matched for age, sex, and state, were analysed separately for African Americans and whites. Odds ratios (ORs) were estimated by logistic regression models for each locus alone and also after adjusting for polymorphisms at adjacent loci. Results: An increased risk of SLE for the IL1a 2889C/C genotype compared with carriage of the 2889T allele was found in both African Americans (OR = 3.1, p = 0.001) and whites (OR = 2.9, p = 0.005). In African Americans, carriage of the IL1b 2511T allele was associated with a higher risk of SLE than carriage of the 2511C/C genotype (OR = 2.4, p = 0.017), independent of variation at IL1a 2889. Conclusions: The observed associations support the hypothesis that genetic variation in IL1 is involved in the aetiology of SLE and merit further investigation.

Genetic Polymorphisms of the Interleukin-1 beta (IL-1.BETA.) -511 and +3954 Single Nucleotide Polymorphisms (SNPs) in Malaysian Systemic Lupus Erythematosus (SLE) Patients

“…31) Contradictory, there were two previous studies based on two different populations in Taiwan and Columbia reporting that there was no significant association. 28,29) In conclusion, our present study, it was observed that the IL-1β −511 and +3954 polymorphisms were significantly associated with the Malaysian SLE patients. The C and E1 alleles for the IL-1β −511 and +3954 polymorphisms, respectively, possessed a higher disease penetration to SLE.…”

“…It was also reported that the combined presence of IL-1α −889 C/C and IL-1β −511 T/T genotypes contributed to an increased risk of getting SLE among the African-Americans, but not in the Whites. 28) In Taiwan, Huang and his group had reported that there was no association between the IL-1β −511 polymorphisms and the susceptibility of SLE. 29) However, our present study of Malaysian SLE patients demonstrated that the C allele was significantly associated to this disease.…”

Interleukin-1β polymorphisms in Colombian patients with autoimmune rheumatic diseases

“…On the contrary, the IL-1b À511 CT genotype and À511T allele were shown to be associated with SLE in African Americans but not in Whites from the Southeastern US. 29 IL-1b þ 3953 polymorphism was not associated with pSS in Finnish patients. 30 In Japanese, genotypes À511 CC and À31 TT were significantly less frequent in pSS patients than in healthy controls and SLE patients.…”

Pathogenic implications for autoantibodies against C-reactive protein and other acute phase proteins

“…In SLE, however, IL-6 levels do not correlate with circulating CRP levels, as is the case in RA [103]. Genetic polymorphisms of CRP-inducing cytokines and their concomitant receptors have been found in association with SLE and might predispose to distinct clinical and immunological features [104][105][106][107].…”