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

Abstract

The role of CCR5Δ32 (rs333) polymorphism in the pathogenesis of systemic lupus erythematosus (SLE) has been evaluated worldwide. The aim of this study was to determine the association between CCR5Δ32 polymorphism with the susceptibility to SLE and the activity of disease in female Southern Brazilian patients. The study enrolled 169 female SLE patients and 132 unrelated female healthy individuals. Baseline clinical, laboratorial characteristics, and the SLE activity (determined using the SLEDAI) were evaluated according to the CCR5Δ32 genotypes. The CCR5Δ32 polymorphism was determined from genomic DNA using a polymerase chain reaction. The frequencies of the genotypes CCR5/CCR5, CCR5/CCR5Δ32, and CCR5Δ32/CCR5Δ32 were 87.6, 11.8, and 0.6 %, respectively, among the patients and 96.2, 3.8, and 0.0 %, respectively, among the controls [CCR5/CCR5 vs. CCR5/CCR5Δ32 + CCR5Δ32/CCR5Δ32: p = 0.0081, odds ratio 3.604 (95 % confidence interval 1.321-9.4836)]. The frequencies of the CCR5 and the CCR5Δ32 alleles were 93.2 and 6.8 % among the patients, and 98.1 and 1.9 % among the controls, respectively (p = 0.0047, OR 3.758, 95 % CI 1.409-10.80). Patients carrying the genotypes with the CCR5Δ32 allele presented earlier age of onset of disease (p = 0.0293) and higher levels of anti-dsDNA (p = 0.0255) than those carrying the wild-type genotype. When the analysis was adjusted for ethnicity, only the age at onset of disease remained significant (p > 0.05). The results suggest that the CCR5Δ32 polymorphism might be associated with SLE genetic predisposition among female Brazilian patients and the age at onset of the disease; however, this genetic variant was not associated with the activity of SLE in this population.

Metabolomics as an Approach to Characterise the Contrasting Roles of CCR5 in the Presence and Absence of Disease

“…In addition, the authors showed that CCR5∆32 genotypes are associated with development of class IV lupus nephritis [123]. Similar results were obtained by Baltus and co-workers [124] in a female Brazilian cohort. The authors investigated the association of CCR5∆32 genotypes with SLE disease susceptibility and disease activity.…”

“…When the authors adjusted the results for the ethnicity of the patients, the authors showed that ethnicity influenced autoimmune responses. However, CCR5∆32 was not associated with disease activity [124]. Lupus nephritis (LN) refers to kidney inflammation and is often a result of SLE.…”

The Role of MECP2 and CCR5 Polymorphisms on the Development and Course of Systemic Lupus Erythematosus

“…The same conclusion was made by Carvalho et al [11] in Portuguese patients. In contrast, Baltus et al [14] claim that CCR5∆32 polymorphism can be considered as a risk factor in female Brazilian patients, and it is linked to the age of SLE onset. Furthermore, Mamtani et al [3] showed that CCR5 haplotype HHG*2, which contains CCR5∆32 polymorphism is connected with an elevated risk of developing systemic lupus erythematosus.…”

“…However, research on the prevalence of CCR5 polymorphisms in SLE patients are ambiguous. The noticeable divergences in role of CCR5 polymorphisms in SLE patients can be explained by different methodology and methods used for testing [14].…”

“…Polymorphisms within the CCR5 and MECP2 genes are associated with the risk of SLE disease onset and they may be also a prognostic factors of SLE severity [7,8,14]. Research in these subjects can improve the diagnosis and prognosis of SLE, which could result in faster and more effective treatment of SLE patients.…”