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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. Wenjuan Tang 1# , Fang Xie 2# , Xiaoli Zeng 1# , Hong Sun 3# , Haibo Zhao 4* 1 Department of Maternal Health Care, Shiyan Maternal and Child Health Hospital, Shiyan, Hubei, PR China 2 Department of Gynaecology, Shiyan Maternal and Child Health Hospital, Shiyan, Hubei, PR China 3 Department of Geriatrics, WuHan hospital of Chinese traditional and western medicine, WuHan, Hubei, PR China 3 Department of Geriatrics, WuHan hospital of Chinese traditional and western medicine, WuHan, Hubei, PR China 4 Department of Paediatric Surgery, Shiyan Maternal and Child Health Hospital, Shiyan, Hubei, PR China # These authors contributed equally to this work Abstract 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. Keywords: CTLA-4, Polymorphism, HIV-1 infection, Viral Load, Immune response. Accepted on November 4, 2016 Introduction Human Immunodeficiency Virus (HIV) causes HIV infection and Acquired Immune Deficiency Syndrome (AIDS). Globally, statistics from the WHO and UNAIDS showed that approximately 2.3 million people became newly infected and 1.6 million died of AIDS-related causes at the end of 2012, meanwhile, there are up to more than 40 million people currently living with HIV infection worldwide [1]. In China in 2014, an estimated 0.448 million Chinese are living with HIV/ AIDS and 0.139 million deaths were registered [2]. HIV continues to be a major global public health issue, and there is no cure for HIV infection by far. Infection with HIV type 1 (HIV-1) typically occurs across mucosal surfaces or by direct inoculation. Once HIV-1 infects a cell, the virus integrates into host genetic material and either begins cycles of replication or ISSN 0970-938X www.biomedres.info Biomed Res- India 2017 Volume 28 Issue 6 2545 Biomedical Research 2017; 28 (6): 2545-2554

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