الملخص الإنجليزي
Genetic variation in the components of innate immunity has an important impact on host-pathogen defense mechanism. Toll-like receptors (TLRs) are essential components of the innate immune response to various infectious diseases, including the human immunodeficiency virus-1 (HIV-1). A number of recent studies have demonstrated that single-nucleotide polymorphisms (SNPs) in TLRs influence CD4 T cell count, viral load and disease progression during HIV infection. Indeed, SNPs in the TLR4 gene (1063 A/G and 1363C/T) were found to be correlated with high viral load. Moreover, a SNP in TLR7 gene (Gln11Leu) has been associated with high viral load and increased disease progression. However, the relation between TLR9 (1635A/G) and CD4 T cells count in AIDS patients is controversial. In this study we investigated: (1) The association of these SNPs with the viral load and CD4 T cells counts in Omani AIDS patients 12 months before reaching VL< 50 copies/ml. (2) Association of these SNPs with immunological outcome of highly active antiretroviral therapy (HAART). (3) The frequency of these SNPs in the Omani healthy individuals in comparison to Omani AIDS patients.
A total of 68 ADS patients and 100 healthy individuals were enrolled in the study. The SNPs were analyzed by sequencing regions, which contain the SNPs, amplified by polymerase chain reaction (PCR). The results showed that the proportion of individuals with the TLR4 1063GG genotype was significantly higher in AIDS group as compared to the control group. However, TLR4 (1063A/G and 1363C/T) SNPs were not associated with the viral load or CD4 T cells count in AIDS patients. In contrast, a significant association between the TLR7 'Leu' allele (TT genotype) in AIDS patients and a higher viral load was observed. Moreover, the presence of TLR7 'Gin' allele (AA genotype) was significantly associated with higher CD4 T cells count during 12 months before reaching VL< 50 copies/ml in normal CD4 T cells count group patients.
Furthermore, the TLRI 1635AG genotype was associated with a higher CD4 T cells count during 12 months before reaching VL< 50 copies/ml in the AIDS cohort, Additionally, the combination of TLR7 GIn (AA) and TLR9 1635 (AG) genotypes was significantly associated with higher CD4 T cells count during 12 months before reaching VL< 50 copies/ml as compared to other genotypes.
These results demonstrate a significant association between SNPs in TLR7 and 9 and CD4 T cells count during viremia period and between TLR7 and the viral load and CD4 T cells count after controlling the viremia because of HAART. Therefore, information on these SNPs among Omani AIDS patients might help optimizing the treatment.
