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CTLA-4 gene polymorphism A/G in exon 1 (+49) is associated with plasma viral load in HIV-1 infection patients

Objective: Cytotoxic T Lymphocyte Antigen 4 (CTLA-4) is a potent immunoregulatory molecule that suppresses antitumor response by down-regulating T cell activation and is believed to have a critical modulatory role in the immune response. The expression and function of CTLA-4 may be affected by gene polymorphisms. The present study examined the correlation of CTLA-4 gene +49 G/A polymorphism with HIV-1 infection, and evaluated the role of +49G/A polymorphism on plasma EFV level and treatment response in the form of change in HIV viral load, CD+4 T-cell counts and CD+4/CD +8 ratios in HIV-1 infected patients receiving Highly Active Antiretroviral Therapy (HAART).

Materials and Methods: The CTLA-4 exon 1 +49 A/G Single Nucleotide Polymorphism (SNPs) were genotyped in 45 adult patients with HIV-1 infection and 50 ethnically, age, gender matched healthy controls through polymerase chain reaction. Plasma EFV levels were detected using high-performance liquid chromatography, and viral load, CD+4 T-cell counts and CD+4/CD+8 ratios were measured at enrolment and every 2 months for 6 months.

Results: Frequencies of the CTLA-4 +49 AG and GG genotype and the +49 G allele were not significantly increased in patients with HIV-1 infection compared to healthy controls (AG andGG vs. AA: Odds Ratio (OR)=1.70, 95% confidence interval (CI): 0.74-3.89, P=0.21; G vs. A: OR=1.45, 95% CI: 0.74-2.82, P=0.28), meanwhile, were not significantly associated with high plasma EFV concentrations (P=0.0236), whereas the GG genotype was associated with higher plasma viral load (P=0.017) and lower CD+4 T-cell counts (P=0.009). The relationship between the reactivation of HIV viral load declines, increased CD+4 T-cell counts and increment ratio of CD+4/CD+8 in peripheral blood were observed.

Conclusions: This study provides the first evidence that CTLA-4 exon 1 +49A/G polymorphism does not represent a major susceptibility risk allele for HIV-1 infection, however, supporting the association with plasma HIV viral load level. Furthermore, the CTLA-4 (+99A/G) gene polymorphism is not associated with immune response to HAART. To validate our results, further studies on a larger cohort are needed.

Author(s): Wenjuan Tang, Fang Xie, Xiaoli Zeng, Hong Sun, Haibo Zhao