CCR5delta32 in systemic lupus erythematosus: implications for disease susceptibility and outcome in a Brazilian population

Abstract

The aim of this study was to analyze the allelic and genotypic frequencies of the CCR5delta32 polymorphism in systemic lupus erythematosus (SLE) patients and to investigate a possible association of this allele with SLE susceptibility and clinical outcome. A total of 367 SLE patients and 435 healthy controls were genotyped for the CCR5delta32 polymorphism. We observed that, in European-derived individuals, the frequency of the CCR5delta32 allele was smaller in patients than in controls (2.7% vs. 7.5%, OR 0.34, 95% CI 0.17-0.65, p Bonf=0.002), suggesting that this allele could be considered a protective factor for the disease. Regarding clinical manifestations, we observed that CCR5delta32 female African-derived carrier patients presented a higher predisposition to class IV nephritis when compared with absent nephritis/other class group (13.8% vs. 3.8%, OR 37.1, 95% CI 2.8-1854.7, p Bonf=0.030). A multivariate analysis including all female patients and controlling for the presence or absence of anti-dsDNA antibodies, ethnicity and age at diagnosis showed an increased relative risk of 3.9 times for patients carrying the CCR5delta32 allele to develop class IV nephritis as compared with noncarriers. Our data suggest that the CCR5delta32 allele is a protective factor for the disease in European-derived patients and a susceptibility factor to class IV nephritis in African-derived female patients.

CCR5Δ32 (rs333) polymorphism is associated with the susceptibility to systemic lupus erythematosus in female Brazilian patients

“…However, a limitation must be considered in this result considering that the ethnicity was self-reported [26]. The overall distribution of CCR5Δ32 genotypes and allele frequency was similar with previous studies carried out in Brazilians [22] and other ethnics SLE patients cohorts [23,24,30]. However, the results varied in these studies regarding the role of this mutation status on SLE susceptibility and severity.…”

“…These results demonstrated that ethnicity is a factor that exerts an effect on the anti-dsDNA serum levels of SLE patients and suggests inter-ethnic genetic contributions to the regulation of autoimmune responses and activity and severity in SLE. The demographic and clinical characteristics of these patients are consistent with previous studies, such as the occurrence of SLE in young females and low SLEDAI [22,23,28,30]. The low SLEDAI presented by the most of the SLE patients is probably a result of the treatment presented by them at the time of inclusion in the study.…”

“…However, the results varied in these studies regarding the role of this mutation status on SLE susceptibility and severity. The CCR5Δ32 allele was suggested to be a protective factor for SLE in Europeanderived patients from Southern Brazil, although patients with the CCR5Δ32 polymorphism had higher chances to develop lupus nephritis type IV [22]. A protective effect of the CCR5Δ32 polymorphism against SLE development was shown among Portuguese patients [30].…”

“…The CCR5Δ32 polymorphism has been evaluated in several autoimmune diseases with conflicting results, including rheumatoid arthritis [13-17, 49, 50], and SLE [16,[22][23][24]. Moreover, the actual role of the Δ32 mutation in CCR5 is confounded by patient's immunological status, other genetic polymorphisms, and epigenetic mechanisms.…”

“…While some studies showed an association with protective effect for disease susceptibility [22], others did not confirm this effect [16,23,24]. Therefore, the aim of this study was to determine the association between the CCR5Δ32 polymorphism with SLE susceptibility and activity in a female cohort of SLE patients from Southern Brazilian population.…”