HIVSNP · Host determinants of susceptibility to HIV-1 infection
6РП — Действия „Мария Кюри“
- Период
- 2005-11-01 → 2007-10-31
- Финансиране от ЕС
- 80 000 €
- Участници
- 1
- Схема
- IRG
Линиите свързват координатора с партньорите. За проекти отпреди 2014 г. CORDIS не винаги дава точни координати. Тези точки са на ниво град или държава.
Накратко на български
Генетичните вариации при хората, като например конкретни единични нуклеотидни полиморфизми (SNP), определят защо някои хора са по-устойчиви на ХИВ или развиват болестта по различен начин. Това помага за по-точна диагностика, прогнозиране на развитието на инфекцията и търсене на нови мишени за лекарства.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Final Activity Report Summary - HIVSNP (Host determinants of susceptibility to HIV-1 infection)
The natural course of HIV-1 infection is widely variable with extremes of disease progression within two years or continuous asymptomatic infection for more than 15 years. Moreover, certain people are relatively resistant to HIV-1 infection despite high levels of sexual risk behaviour. To identify host factors that influence this variability in outcome, we designed a genome-wide association study in the Amsterdam cohort studies on HIV infection and AIDS (ACS). We tested approximately 300 000 single nucleotide polymorphisms (SNPs) in 335 HIV-1 infected homosexual men, 120 HIV-1 infected intravenous drug users and 50 HRSN. One SNP, rs1570023 in the C20orf151/Cables2 gene region, was significantly associated with HIV-1 disease course. Further in depth analysis of this large data set is likely to reveal additional associations. Apart from the identification of novel host factors, we also used this data set to confirm the reported association between SNPs in HLA-C and HCP5 gene regions with viral load at set point. Moreover, we found these SNPs to be correlated with HIV-1 disease course. The exact mechanism by which these SNPs, or the gene region they tag, influence disease progression remains to be established. These results emphasise the importance of studying human genetic variations as a tool to find new host genetic factors in infectious diseases. GWA studies may reveal genes that can be considered new targets for drug development. In addition, SNPs strongly associated with HIV-1 disease progression, may be applied in routine diagnostics to predict the disease course and to determine for instance if antiviral therapy should be initiated early in infection. Indeed, screening for polymorphisms in the human genome that influence the course of infection may allow better fine-tuning of patient management.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
The natural course of HIV-1 infection is widely variable with extremes of disease progression within 2 years or continuous asymptomatic infection for more than 15 years. Moreover, certain people are relatively resistant to HIV-1 infection despite high levels of sexual risk behaviour (high risk seronegatives, HRSN). In the majority of cases, the underlying mechanism responsible for the variable outcome of exposure to HIV-1 infection is not known. We hypothesize that host factors that either restrict or enable HIV-1 replication will be additional targets for therapeutic intervention. In the present study we will focus on the role of host factors in determining HIV-1 susceptibility using genome-wide single nucleotide polymorphism (SNP) analysis.Participants of the Amsterdam Cohort Studies (ACS) have accurately documented levels of risk behaviour, moment of seroconversion for HIV antibodies and detailed follow up information on virological, immunological and clinical parameters, treatment history and disease course. Initially, we will perform SNP analyses on HRSN and the relevant control group, low risk seropositives (LRSP). In addition, CD4+ T cells from several of our HRSN participants have shown reduced susceptibility to HIV-1 in vitro. As host factors responsible for this reduced in vitro susceptibility may also be relevant in vivo, we will test in vitro HIV-1 susceptibility of blood cells from family members of these HRSN and LRSP to extend SNP analysis to these family members to increase the power of our analysis. Altogether, this will provide a genome-wide analysis of host polymorphisms that could be relevant to HIV infection.
Оригинален текст от CORDIS (на английски).
Участници
- SANQUIN BLOOD SUPPLY FOUNDATION · AMSTERDAMКоординаторНиво градНидерландия
Връзки
Данни: CORDIS, © Европейски съюз