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The Association of Interleukin-27 and HIV Infection in Chinese

Posted on:2013-08-30Degree:Ph.DType:Dissertation
University:The Chinese University of Hong Kong (Hong Kong)Candidate:He, LaiFull Text:PDF
GTID:1454390008471874Subject:Health Sciences
Abstract/Summary:
Human Immunodeficiency Virus (HIV) is the causative agent of Acquired Immunodeficiency Syndrome (AIDS); HIV/AIDS caused 1.8 million deaths world-widely in 2010 and became a major global health challenge. HIV co-infections with Hepatitis B virus (HBV), Hepatitis C virus (HCV) are common and have emerged into new health problems with severe clinical consequences. Since the discovery of HIV, massive progress in understanding of the pathogen has been achieved. Due to the restriction of research model, how human immune system responds to HIV infection, particularly, to HBV or HCV co-infections is still worthy further elucidation.;A cohort study was first conducted in Shenzhen regarding the seroprevalence of HBV, HCV infections among HIV-infected population. Totally 914 HIV positive individuals were recruited in the study and tested for HBsAg and anti-HCV antibodies. The results showed a 10.9% (100/914) HIV/HBV co-infection rate, 14.6% (133/914) HIV/HCV co-infection prevalence and 3.7% (34/914) HIV/HBV/HCV triple-infection prevalence. Multivariate logistic regression revealed that HIV transmission risk behavior was significantly associated with HIV, HBV, HCV co-infections. Most HIV/HBV co-infection cases got HIV through sexual contact including heterosexual and homosexual behaviors (95/100, 95%); while most HIV/HCV co-infection subjects were injection drug users (IDUs) (89/133, 66.9%). In the case of HIV/HBV/HCV triple-infection, IDUs accounted for a large ratio (28/34, 82.4%). Among IDUs, most of them were male (108/122, 88.5%) and nearly half were aged 27 to 32 years old (56/122, 45.9%). Near half people who got HIV through blood and blood products were HIV/HCV co-infected (10/23, 43.5%). Gender has a significant correlation with HIV risk behavior and most IDUs were male.;Next, we applied ELISA to test HIV positive clinical samples and proved that plasma interleukin-27 (IL-27) level was significantly elevated in HIV mono-infected, HIV/HBV co-infected and HIV/HCV co-infected subjects when compared with healthy controls. Later, we further revealed that plasma IL-27 titer was not significantly varied among HIV, HBV and HCV co-infections except between HIV/HCV co-infections and HIV/HBV/HCV triple-infections. We also observed a significant positive correlation between CD4+ T cell counts and plasma IL-27 titer within HIV mono-infected group (r = 0.177, P = 0.034).;We further analyzed the impact HIV and HCV viral loads on plasma IL-27 titer. We found there was no significant correlation between HIV viral load and IL-27 titer among HIV mono-infected individuals (r = - 0.063, P = 0.679); while a significant positive correlation was observed between HIV viral load and IL-27 titer in HIV/HCV co-infected individuals (r = 0.362, P = 0.049). In the case of HIV/HCV co-infection, there was no significant linear correlation between HIV and HCV viral loads (r = - 0.072, P = 0.704) but exist obvious subdivision of samples in terms of HIV and HCV viral loads with significant IL-27 titer variance (P = 0.014). No correlation was observed between HCV viral load and IL-27 titer (r = - 0.119, P = 0.530).;IL-27 p28 polymorphisms were genotyped with TaqManRTM Allelic Discrimination Assay in Chinese men who have sex with men (MSM) population in Shenzhen and the results revealed that proportions of IL-27 p28 -964A/G and 4603G/A genotypes were not significantly different from the healthy controls; IL-27 p28 -964A/G and 4603G/A allele frequencies were similar between HIV positive MSM group and healthy control MSM group. Results also showed that for IL-27 p28 2905T/G polymorphism, TG genotype has a 2.77-fold decreased risk of HIV susceptibility and subjects with G allele has a 2.72-fold decreased risk of HIV susceptibility. Linkage disequilibrium (LD) coefficients were observed between IL-27 p28 -964A/G and 2905T/G (|D'| = 0.942), -964A/G and 4603G/A (|D'| = 0.930). Haplotype analyses revealed that haplotype GGG has a protective role against HIV infection in MSM population (OR = 0.313; P < 0.001).;In conclusion, the seroprevalences of HBV and HCV infection among HIV positive population in Shenzhen were surveyed and risk factors associated with co-infections were analyzed. Plasma IL-27 titer was significantly elevated in HIV mono-infected, HIV/HBV co-infected and HIV/HCV co-infected individuals. IL-27 level was correlated with CD4+ T cell counts within HIV mono-infected people. A significant positive correlation was found between HIV viral load and IL-27 titer in HIV/HCV co-infected individuals (r = 0.362, P = 0.049). IL-27 p28 2905T/G was associated with individual susceptibility to HIV infection and haplotype GGG showed a protective role in restricting HIV infection in MSM population.
Keywords/Search Tags:HIV, IL-27 titer, HCV viral loads, MSM, HBV, -964A/G and 4603G/A, Population
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