Abstract

Vertical HIV transmission does not occur in all exposed infants. Many infants remain HIV uninfected even after exposure. This is partly attributed to the host genes involving cytokine production, which is rarely documented in vertical transmission. Here, an observational cohort study evaluated whether polymorphisms in cytokine, receptor and antagonist genes are associated with perinatal HIV transmission. Single nucleotide polymorphism (SNP) genotyping was performed via the polymerase chain reaction with sequence-specific primers method. Haplotype block structure was determined and statistical analysis was performed using appropriate software in each case. Twenty-two SNPs were analysed in 30 seropositive and 61 seronegative children. Confounding factors such as mother's viral load, treatment regimen, breast feeding options, etc., were documented. Analysis revealed the association of two SNPs: IL1R1 (rs2234650) and TNFA (rs1800629) with vertical HIV transmission. CT genotype at IL1R1 was observed at a higher frequency in positive children (76.66% versus 42.62%, p=0.002), whereas the CC genotype was significantly increased in exposed uninfected children (47.54% versus 16.66%, p=0.004). Similarly, the GG genotype of TNFA was significantly higher in uninfected children compared to infected ones (76.66% versus 46.66%, p=0.005), whereas the GA genotype frequency was higher among infected children (53.33% versus 21.66%, p=0.003). The frequency of the 'G' allele of TNFA and 'C' allele of IL1R1 was significant (p=0.018) in negative children. Haplotypes of SNPs belonging to IL1, TNFA and IL4 were also found to associate with transmission. The present study confirms the association of SNPs IL1R1 (rs2234650) and TNFA (rs1800629) with the risk of vertical transmission. These SNPs can be exploited as possible predictive markers of HIV transmission.

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