Interleukin 7 receptor (IL7R) is vital in the adaptive immune response against human immunodeficiency viruses (HIV). We assessed IL7RA polymorphisms (SNPs) in antiretroviral therapy (ART)-naïve HIV patients for their association with spontaneous HIV infection control. We conducted a retrospective cohort study involving 667 ART-naïve patients categorized by HIV progression (ordinal variable): 150 rapid progressors, 334 moderate/typical progressors, 86 long-term nonprogressors elite controllers (LTNPs-EC), and 97 LTNPs-non-EC. We genotyped three IL7RA SNPs using Agena Bioscience's MassARRAY platform. The association between IL7RA SNPs and spontaneous HIV infection control was evaluated using ordinal logistic regression. Individuals carrying the rs10491434 G allele have a higher likelihood of spontaneous HIV infection control (adjusted odds ratio [aOR] = 1.33; p = 0.023). Moreover, the IL7RA GCT haplotype, consisting of three specific SNPs (rs6897932, rs987106, and rs10491434), demonstrated an association with the control of untreated HIV infection (aOR = 1.34; p = 0.050). Remarkably, the rs10491434 SNP and the IL7RA GCT haplotype exhibited similar aOR values, suggesting that rs10491434 may be primarily responsible for the observed effect of the haplotype. IL7RA rs10491434 G allele is associated with a higher likelihood of spontaneous HIV infection control, indicating its significant role in the pathogenesis of HIV, possibly influencing infection course and viral replication control.
HIV Infections , Interleukin-7 Receptor alpha Subunit , Humans , Disease Progression , HIV Infections/genetics , HIV Infections/therapy , Infection Control , Polymorphism, Single Nucleotide , Retrospective Studies , Interleukin-7 Receptor alpha Subunit/genetics
IRF5-TNPO3 polymorphisms have previously been related to immune response, and TNPO3 plays a role in human immunodeficiency virus (HIV)-1 infection after nuclear import. Therefore, we analyzed the genetic association between IRF5-TNPO3 polymorphisms and the HIV elite control in long-term nonprogressors (LTNPs). We performed a retrospective cohort study on 183 LTNPs, who were antiretroviral therapy-naïve with CD4+ ≥ 500 cells/mm3 , viral load ≤10 000 copies/mL, and asymptomatic over 10 years after HIV seroconversion. The primary outcome variable was HIV elite control (undetectable viral load in at least 90% of the measurements for at least 1 year). Seven IRF5-TNPO3 polymorphisms were genotyped using Agena Bioscience's MassARRAY platform. We found a significant association between specific IRF5-TNPO3 genotypes and HIV elite control: rs2004640 TT (aOR = 2.05; p = 0.041), rs10954213 AA (aOR = 1.95; p = 0.035), rs2280714 TT (aOR = 2.02; p = 0.031), and rs10279821 CC (aOR = 2.12; p = 0.017). We also found a significant association between IRF5-TNPO3 haplotype TATC composed of the favorable significant polymorphisms (rs2004640, rs10954213, rs2280714, and rs10279821) and the HIV elite control (aOR = 1.59; p = 0.048). IRF5-TNPO3 rs2004640, rs10954213, rs2280714, and rs10279821 polymorphisms were related to HIV elite control in LTNPs. Our data provide new knowledge about the impact of IRF5-TNPO3 polymorphisms on HIV pathogenesis to understand the phenomenon of natural HIV control.
HIV Infections , Humans , Retrospective Studies , Polymorphism, Single Nucleotide , Interferon Regulatory Factors/genetics , Genotype , Genetic Predisposition to Disease , beta Karyopherins/genetics
BACKGROUND: Our aim was to determine whether α-chain of the IL-7 receptor (IL7RA) polymorphisms (rs10491434, rs6897932 and rs987106) are associated with the clinical pattern of AIDS progression in ART-naïve HIV-infected patients. MATERIALS AND METHODS: We carried out a cross-sectional study in 673 HIV-infected patients who were classified into three groups according to the clinical pattern of AIDS progression (188 long-term nonprogressors (LTNPs), 334 moderate progressors (MPs) and 151 rapid progressors (RPs)). Additionally, 134 healthy blood donors participated as a Control-group. We selected three IL7RA polymorphisms located at three regulatory regions [rs6897932 (exon 6), rs987106 (intronic region) and rs10491434 (3'UTR)]. DNA genotyping was performed using Sequenom's MassARRAY platform. RESULTS: The Control-group and all HIV-infected patients had similar age and percentage of males. LTNP-group was older at HIV diagnosis and at the inclusion in the study and had higher percentage of intravenous drug users (IDU) (P < 0·001). Besides, LTNP-group had lower proportion of male patients and homosexual HIV transmission than MP and RP groups (P < 0·001). Moreover, similar values of allelic, genotypic and haplotype frequencies for IL7RA polymorphisms were found between healthy controls and HIV-infected patients (P > 0·05), and among different subgroups of HIV patients according to AIDS progression (LTNPs, MPs and RPs) (P > 0·05). The adjusted logistic regression did not show any significant association between IL7RA polymorphisms and AIDS progression. CONCLUSIONS: IL7RA polymorphisms (rs6897932, rs987106 and rs10491434) were not associated with AIDS progression in Spanish population. Therefore, IL7RA polymorphisms do not seem to help us to understand HIV pathogenesis in untreated HIV-infected patients with different clinical evolution.
Gene Expression Regulation , HIV Infections/genetics , HIV Infections/mortality , Interleukin-7 Receptor alpha Subunit/genetics , Polymorphism, Single Nucleotide , Acquired Immunodeficiency Syndrome/diagnosis , Acquired Immunodeficiency Syndrome/genetics , Acquired Immunodeficiency Syndrome/mortality , Adult , Age Factors , Cross-Sectional Studies , Disease Progression , Female , HIV Infections/diagnosis , Humans , Logistic Models , Male , Middle Aged , Prognosis , Reference Values , Risk Assessment , Sensitivity and Specificity , Sex Factors , Spain , Survival Analysis
