High frequency of the CCR5delta32 variant among individuals from an admixed Brazilian population with sickle cell anemia

Abstract

Homozygous sickle cell disease (SCD) has a wide spectrum of clinical manifestations. In Brazil, the main cause of death of individuals with SCD is recurrent infection. The CCR5D32 allele, which confers relative resistance to macrophage-tropic HIV virus infection, probably has reached its frequency and world distribution due to other pathogens that target macrophage in European populations. In the present investigation a relatively higher prevalence (5.1%) of the CCR5D32 allele was identified, by PCR amplification using specific primers, in 79 SCD patients when compared to healthy controls (1.3%) with the same ethnic background (Afro-Brazilians). Based on a hypothesis that considers SCD as a chronic inflammatory condition, and since the CCR5 chemokine receptor is involved in directing a Th1-type immune response, we suggest that a Th1/Th2 balance can influence the morbidity of SCD. If the presence of the null CCR5D32 allele results in a reduction of the chronic inflammation state present in SCD patients, this could lead to differential survival of SCD individuals who are carriers of the CCR5D32 allele. This differential survival could be due to the development of less severe infections and consequently reduced or less severe vaso-occlusive crises. Correspondence

CCR5 genotypes and progression to HIV disease in perinatally infected children

“…The prevalence of the heterozygous allele in this group of children of different ethnic origins was 4%, comparable to the findings for various studies in Brazilian adults (5% in blood donors [18], and 5.1% in patients with falciform anemia [19]). Silva et al reported a 6.5% incidence of the heterozygous genotype among blood donors from São Paulo city, Brazil.…”

Chemokine receptor 5 (CCR5) delta 32 polymorphism in lupus nephritis: A large case-control study and meta-analysis

“…Characterization of CCR5 D32 genotypes was performed by polymerase chain reaction (PCR) with forward primer 5 0 -GGTCTTCATTACACCTGC-3 0 and reverse primer 5 0 -AGGATTCCCGAGTAGCAGATG-3 0 flanking the 32-nucleotide deletion in the CCR5 gene as previously described [28]. Briefly, samples were amplified in a volume of 25 ml, containing 1 Â Taq PCR MasterMix, and 0.2 mM forward and reverse primers.…”

Frequency of CCR5delta32 in Brazilian populations

“…Samples were submitted to 40 cycles of 1 min at 94ºC, 1 min at 55ºC, and 1 min at 72ºC. The set of specific primers used to amplify the CCR5 gene segment was described by Chies and Hutz (6). It yields a 137-bp fragment for the wild-type allele and a 105-bp fragment for the CCR5∆32 variant.…”