Abstract
This study evaluated four polymorphisms located in the DC-SIGN (CD209) gene promoter region (positions −336, −332 −201 and −139) in DNA samples from four Brazilian ethnic groups (Caucasians, Afro-Brazilian, Asians and Amerindians) to establish the population distribution of these single-nucleotide polymorphisms (SNPs) and correlated DC-SIGN polymorphisms and infection in samples from human T-cell lymphotropic virus type 1 (HTLV-1)-infected individuals. To identify CD209 SNPs, 452 bp of the CD209 promoter region were sequenced and the genotype and allelic frequencies were evaluated. This is the first study to show genetic polymorphism in the CD209 gene in distinct Brazilian ethnic groups with the distribution of allelic and genotypic frequency. The results showed that −336A and −139A SNPs were quite common in Asians and that the −201T allele was not observed in Caucasians, Asians or Amerindians. No significant differences were observed between individuals with HTLV-1 disease and asymptomatic patients. However, the −336A variant was more frequent in HTLV-1-infected patients [HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), 80 %; healthy asymptomatic HTLV-1 carriers, 90 %] than in the control group (70 %) [P=0.0197, odds ratio (OR)=2.511, 95 % confidence interval (CI)=1.218–5.179). In addition, the −139A allele was found to be associated with protection against HTLV-1 infection (P=0.0037, OR=0.3758, 95 % CI=0.1954–0.7229) when the HTLV-1-infected patients as a whole were compared with the healthy-control group. These observations suggest that the −139A allele may be associated with HTLV-1 infection, although no significant association was observed among asymptomatic and HAM/TSP patients. In conclusion, the variation observed in SNPs −336 and −139 indicates that this lectin may be of crucial importance in the susceptibility/transmission of HTLV-1 infections.
Highlights
Dendritic cells (DCs) are professional antigen-processing cells that act against invading pathogens (Banchereau & Steinman, 1998), being important as initiators and modulators of the immune response
DCSIGN [DC-specific intercellular adhesion molecule 3 (ICAM-3)-grabbing non-integrin], encoded by a member of the CD209 gene family, is a receptor on DCs that binds to ICAM-3, which is expressed on T cells to facilitate the initial interaction between DCs and T cells (Soilleux et al, 2002)
We investigated four polymorphisms located in the CD209 promoter region at positions 2336, 2332, 2201 and 2139 that are known to be associated with susceptibility/ resistance to pathogens
Summary
Dendritic cells (DCs) are professional antigen-processing cells that act against invading pathogens (Banchereau & Steinman, 1998), being important as initiators and modulators of the immune response. DCs are efficient stimulators of T and B cells. DCs are produced in bone marrow and migrate to the tissues, where they capture and process the antigens. Ceccaldi et al (2006) demonstrated that DC-SIGN is an important co-factor that facilitates the fusion between HTLV-1-infected cells and DCs through ICAM-dependent mechanisms.
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