CCR5-Δ32 genetic polymorphism associated with benign clinical course and magnetic resonance imaging findings in Brazilian patients with multiple sclerosis

Abstract

Abstract. The CCR5 chemokine receptor has been implicated in the pathogenesis of multiple sclerosis (MS). This research was carried out to investigate the association between the CCR5-Δ32 deletion in 124 patients with MS from Southern Brazil. Ninety-eight (79.0%) patients presented with relapsingremitting MS (RR-MS), 17 (13.7%) secondary progressive MS (SP-MS), 8 (6.5%) primary progressive MS (PP-MS) and one (0.8%) clinically isolated syndrome (CIS). The control group consisted of 127 healthy blood donors from the same geographic region. The disease severity was assessed clinically using the Expanded Disability Status Scale (EDSS). Genomic DNA was extracted from peripheral blood cells and the genetic polymorphism was evaluated by polymerase chain reaction. Of the MS patients, 85 (68.5%) were females (p=0.0093). The CCR5-Δ32 frequency among the controls was 5.5%, and did not differ from that observed among the MS patients (4.8%) (p=0.7337). The mean (±SD) age at disease onset among the carriers and non-carriers of the CCR5-Δ32 allele was 31.7 (±11.1) and 36.6 (±12.0) years, respectively (p=0.1312). The duration (±SD) of the disease was 11.2 (±12.9) and 7.7 (± 5.6) years among the CCR5-Δ32 heterozygous, and CCR5 wild type, respectively (p=0.396). The mean (±SD) EDSS among the MS patients carriers and non-carriers of the CCR5-Δ32 allele was 2.4±1.2 and 2.67±2.2, respectively (p=0.9796). The MRI findings in MS patients with the CCR5-Δ32 genotype exhibited lower positive gadolinium enhancing-imaging (p=0.0013) and lower brain atrophy (p=0.1333) than MS patients with the CCR5 wild-type genotype. Despite that the differences were not significant, the results suggested that the disease onset and progression to disability may be prolonged in MS carriers of CCR5-Δ32, and CCR5-Δ32 could be considered a favorable prognostic biomarker of MS. Further studies comprising larger numbers of individuals carrying non-wild-type haplotypes are needed to determine CCR5-Δ32 involvement in the specific process of MS pathology and pathogenesis.

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

“…In juvenile idiopathic arthritis subtypes, the CCR5Δ32 does not have a protective effect, but instead it could be a factor associated with more inflammatory forms of the disease [18]. Conflicting results of the association between the CCR5Δ32 allele and multiple sclerosis were also reported [19][20][21].…”

“…CCR5 gene was amplified using polymerase chain reaction (PCR), and a fragment with 225 base pairs was obtained using the primers sense 5′-ACC AGA TCT CAA AAA GAA-3′ and antisense 5′-CAT GAT GGT GAA GAT AAG CTT CA-3′) (Invitrogen™, Life Technologies, Carlsbad, CA, USA) as previously reported [21]. PCR was performed in a thermocycler (Applied Biosystems Veriti™ 96-Well Thermal Cycler, Life Technologies, Foster City, CA, USA), as previously reported [21]. PCR products were analyzed by electrophoresis in 3 % agarose gel and visualized on an ultraviolet transilluminator, after staining with 1 % ethidium bromide.…”

CCR5 and p53 codon 72 gene polymorphisms: Implications in breast cancer development

“…The CCR5D32 variant results in a nonfunctional form of the chemokine receptor that is incapable of binding ß-chemokines (Rantes, MIP-1·, MIP-1ß). CCR5D32 causes significant defects in the chemotaxis mediated by these ligands and has been implicated in a variety of immune-mediated diseases (9)(10)(11).…”

Genetic polymorphisms associated with the development and clinical course of multiple sclerosis (Review)

“…The association between the CCR5-∆32 allele with the clinical course and mri was analyzed in 124 unrelated mS outpatients (evaluated by the edSS for the disease severity), and in 127 unrelated healthy blood donors from a similar geographical area, located in londrina, southern Brazil (15). The frequency of the CCR5 wild-type and CCR5-∆32 heterozygous genotypes was 90.4 and 9.6%, respectively, in mS patients.…”

“…the mS incidence is ~2 or 3-fold higher in women than men and in patients with late onset, the rate seems to equalize (1,(14)(15)(16)(17). epidemiological studies suggest that mS etiology is multifactorial with a complex interaction between environmental factors, such as infectious agents, and genetic factors (14).…”