Abstract
Cytomegalovirus retinochoroiditis (CMV-R) is the primary cause of blindness among AIDS patients. Since HLA-G is associated with the modulation of the immune response, we hypothesized that variability at the 3′ untraslated region (3′UTR) of the gene could be implicated on the predisposition to CMV-R. We evaluated whether HLA-G 3′UTR influences CMV-R development in Brazilian AIDS patients. Peripheral blood DNA was obtained from two groups of patients: (1) AIDS exhibiting CMV-R (n = 40) and (2) AIDS without CMV-R (n = 147). HLA-G 3′UTR typing was performed using sequencing analysis. Allele, genotype and haplotype frequencies were evaluated using Fisher’s exact test accompanied by the calculation of the odds ratio and its 95% confidence interval (95% CI). The etiologic (EF) and preventive fractions were also estimated. Compared to AIDS patients without CMV-R, AIDS patients with CMV-R showed increased frequencies of the: (1) + 3001T allele, (2) the + 3001C/T genotype and (3) the UTR-17 (InsTTCCGTGACG) haplotype (EFs = 0.02–0.04). The UTR-3 (DelTCCGCGACG) haplotype was associated with protection against CMV-R development. Although the risk for developing CMR-V at the population level was relatively low (EF), the identification of HLA-G 3′UTR variation sites may help to further evaluate the role of post-transcriptional factors that may contribute to the existent immunosuppresion caused by HIV per se.
Highlights
Cytomegalovirus retinochoroiditis (CMV-R) is the primary cause of blindness among AIDS patients
The + 3001T allele was overrepresented in CMV-R AIDS patients compared to AIDS without CMV-R (P = 0.046), conferring an Odds Ratio (OR) 18.631 and an Etiologic Fraction = 0.024
The + 3001CC was underrepresented in CMV-R AIDS patients when compared to patients with AIDS without CMV-R (P = 0.045, OR 0.053, 95% confidence interval (95% CI) 0.002–1.117) conferring a Preventive Fraction = 0.945, whereas the + 3001CT was overrepresented in same comparison (P = 0.045, OR 19.026, 95% CI 0.895–404.579, conferring an Etiologic Fraction = 0.047)
Summary
Cytomegalovirus retinochoroiditis (CMV-R) is the primary cause of blindness among AIDS patients. We evaluated whether HLA-G 3′UTR influences CMV-R development in Brazilian AIDS patients. The risk for developing CMR-V at the population level was relatively low (EF), the identification of HLA-G 3′UTR variation sites may help to further evaluate the role of post-transcriptional factors that may contribute to the existent immunosuppresion caused by HIV per se. Cytomegalovirus retinochoroiditis (CMV-R) primarily affects patients with AIDS exhibiting CD4 cell counts < 50 cells/mm[3]. Variation sites at the HLA-G promoter or 3′ untranslated region (3′UTR) may affect transcriptional and post-transcriptional gene control by modifying target sites for transcription factors and microRNAs, respectively[4]. Nucleotide polymorphisms (SNP) at the p romoter[5] and at least 16 variation sites at 3′UTR have been described for the HLA-G gene[6]
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