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Polymorphisms in the regulatory region of the Cyclophilin A gene influence the susceptibility for HIV-1 infection.

Rits MA, van Dort KA, Kootstra NA - PLoS ONE (2008)

Bottom Line: We screened participants of the ACS for the C1604G and A1650G polymorphisms in the regulatory regions of CypA.The prevalence of the 1650G allele was significantly higher in high risk seronegative MSM than in HIV-1 infected MSM.Interestingly, participants of the ACS-DU who carried the 1604G allele showed a significantly accelerated progression when viral RNA load above 10(4.5) copies per ml plasma was used as an endpoint in survival analysis.

View Article: PubMed Central - PubMed

Affiliation: Department of Experimental Immunology, Sanquin Research, Landsteiner Laboratory, and Center for Infectious Diseases and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

ABSTRACT

Background: Previous studies have demonstrated an association between polymorphisms in the regulatory regions of Cyclophilin A (CypA) and susceptibility to both HIV-1 infection and disease progression. Here we studied whether these polymorphisms are associated with susceptibility to HIV-1 infection and disease progression in the Amsterdam Cohort on HIV-1 infection and AIDS (ACS) in a group of men having sex with men (MSM) and drug users (DU).

Methodology/principal findings: We screened participants of the ACS for the C1604G and A1650G polymorphisms in the regulatory regions of CypA. The prevalence of the 1650G allele was significantly higher in high risk seronegative MSM than in HIV-1 infected MSM. However, C1604G or A1650G were not associated with the clinical course of infection in MSM of the ACS. Interestingly, participants of the ACS-DU who carried the 1604G allele showed a significantly accelerated progression when viral RNA load above 10(4.5) copies per ml plasma was used as an endpoint in survival analysis.

Conclusion/significance: The results obtained in this study suggest that the A1650G polymorphism in the regulatory region of the CypA gene may be associated with protection from HIV-1 infection, while the 1604G allele may have a weak association with the clinical course of infection in DU.

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Related in: MedlinePlus

Survival analysis for C1604G and A1650G in DU of the ACS.Kaplan Meier analysis for time in months from seroconversion to viral RNA load above 104.5 copies per ml plasma in DU of the ACS based on the C1604G genotype (left panel) or A1650G genotype (right panel). Black lines indicate individuals homozygous for the major allele (left panel: 1604CC; right panel: 1650AA); Gray lines indicate individuals heterozygous for the minor allele (left panel: 1604CG; right panel: 1650AG).
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pone-0003975-g001: Survival analysis for C1604G and A1650G in DU of the ACS.Kaplan Meier analysis for time in months from seroconversion to viral RNA load above 104.5 copies per ml plasma in DU of the ACS based on the C1604G genotype (left panel) or A1650G genotype (right panel). Black lines indicate individuals homozygous for the major allele (left panel: 1604CC; right panel: 1650AA); Gray lines indicate individuals heterozygous for the minor allele (left panel: 1604CG; right panel: 1650AG).

Mentions: Also in participants of the ACS-DU, the minor alleles of C1604G and A1650G were not associated with progression to a first CD4+ T cell count below 200 cells per µl blood, or clinical AIDS (table 3). However, carriers of the minor allele of C1604G showed a significantly accelerated progression towards a viral RNA load above 104.5 copies per ml plasma (log rank p = 0.007, RH 2.55, CI95% 1.252–5.171; p = 0.01) (Figure 1, table 3). DU carrying the A1650G minor allele tended to have a somewhat slower progression towards viral RNA load above 104.5 copies per ml plasma, albeit not statistically significant (Figure 1, table 3). No significant association between CD4+ T-cells or RNA setpoint and the C1604G or A1650G polymorphism was observed (data not shown).


Polymorphisms in the regulatory region of the Cyclophilin A gene influence the susceptibility for HIV-1 infection.

Rits MA, van Dort KA, Kootstra NA - PLoS ONE (2008)

Survival analysis for C1604G and A1650G in DU of the ACS.Kaplan Meier analysis for time in months from seroconversion to viral RNA load above 104.5 copies per ml plasma in DU of the ACS based on the C1604G genotype (left panel) or A1650G genotype (right panel). Black lines indicate individuals homozygous for the major allele (left panel: 1604CC; right panel: 1650AA); Gray lines indicate individuals heterozygous for the minor allele (left panel: 1604CG; right panel: 1650AG).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2599883&req=5

pone-0003975-g001: Survival analysis for C1604G and A1650G in DU of the ACS.Kaplan Meier analysis for time in months from seroconversion to viral RNA load above 104.5 copies per ml plasma in DU of the ACS based on the C1604G genotype (left panel) or A1650G genotype (right panel). Black lines indicate individuals homozygous for the major allele (left panel: 1604CC; right panel: 1650AA); Gray lines indicate individuals heterozygous for the minor allele (left panel: 1604CG; right panel: 1650AG).
Mentions: Also in participants of the ACS-DU, the minor alleles of C1604G and A1650G were not associated with progression to a first CD4+ T cell count below 200 cells per µl blood, or clinical AIDS (table 3). However, carriers of the minor allele of C1604G showed a significantly accelerated progression towards a viral RNA load above 104.5 copies per ml plasma (log rank p = 0.007, RH 2.55, CI95% 1.252–5.171; p = 0.01) (Figure 1, table 3). DU carrying the A1650G minor allele tended to have a somewhat slower progression towards viral RNA load above 104.5 copies per ml plasma, albeit not statistically significant (Figure 1, table 3). No significant association between CD4+ T-cells or RNA setpoint and the C1604G or A1650G polymorphism was observed (data not shown).

Bottom Line: We screened participants of the ACS for the C1604G and A1650G polymorphisms in the regulatory regions of CypA.The prevalence of the 1650G allele was significantly higher in high risk seronegative MSM than in HIV-1 infected MSM.Interestingly, participants of the ACS-DU who carried the 1604G allele showed a significantly accelerated progression when viral RNA load above 10(4.5) copies per ml plasma was used as an endpoint in survival analysis.

View Article: PubMed Central - PubMed

Affiliation: Department of Experimental Immunology, Sanquin Research, Landsteiner Laboratory, and Center for Infectious Diseases and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

ABSTRACT

Background: Previous studies have demonstrated an association between polymorphisms in the regulatory regions of Cyclophilin A (CypA) and susceptibility to both HIV-1 infection and disease progression. Here we studied whether these polymorphisms are associated with susceptibility to HIV-1 infection and disease progression in the Amsterdam Cohort on HIV-1 infection and AIDS (ACS) in a group of men having sex with men (MSM) and drug users (DU).

Methodology/principal findings: We screened participants of the ACS for the C1604G and A1650G polymorphisms in the regulatory regions of CypA. The prevalence of the 1650G allele was significantly higher in high risk seronegative MSM than in HIV-1 infected MSM. However, C1604G or A1650G were not associated with the clinical course of infection in MSM of the ACS. Interestingly, participants of the ACS-DU who carried the 1604G allele showed a significantly accelerated progression when viral RNA load above 10(4.5) copies per ml plasma was used as an endpoint in survival analysis.

Conclusion/significance: The results obtained in this study suggest that the A1650G polymorphism in the regulatory region of the CypA gene may be associated with protection from HIV-1 infection, while the 1604G allele may have a weak association with the clinical course of infection in DU.

Show MeSH
Related in: MedlinePlus