79 research outputs found
Genetic Variants in Nuclear-Encoded Mitochondrial Genes Influence AIDS Progression
Background: The human mitochondrial genome includes only 13 coding genes while nuclear-encoded genes account for 99% of proteins responsible for mitochondrial morphology, redox regulation, and energetics. Mitochondrial pathogenesis occurs in HIV patients and genetically, mitochondrial DNA haplogroups with presumed functional differences have been associated with differential AIDS progression. Methodology/Principal Findings: Here we explore whether single nucleotide polymorphisms (SNPs) within 904 of the estimated 1,500 genes that specify nuclear-encoded mitochondrial proteins (NEMPs) influence AIDS progression among HIV-1 infected patients. We examined NEMPs for association with the rate of AIDS progression using genotypes generated by an Affymetrix 6.0 genotyping array of 1,455 European American patients from five US AIDS cohorts. Successfully genotyped SNPs gave 50% or better haplotype coverage for 679 of known NEMP genes. With a Bonferroni adjustment for the number of genes and tests examined, multiple SNPs within two NEMP genes showed significant association with AIDS progression: acyl-CoA synthetase medium-chain family member 4 (ACSM4) on chromosome 12 and peroxisomal D3,D2-enoyl- CoA isomerase (PECI) on chromosome 6. Conclusions: Our previous studies on mitochondrial DNA showed that European haplogroups with presumed functional differences were associated with AIDS progression and HAART mediated adverse events. The modest influences of nuclearencoded mitochondrial genes found in the current study add support to the idea that mitochondrial function plays a role in AIDS pathogenesis
Long-term major joint outcomes in young adults with haemophilia: interim data from the HGDS
Monitoring bypassing agent therapy – a prospective crossover study comparing thromboelastometry and thrombin generation assay
CYTOMEGALOVIRUS-INFECTION AND RISK OF AIDS IN HUMAN-IMMUNODEFICIENCY-VIRUS - INFECTED HEMOPHILIA PATIENTS
The effects of prevalent and incident cytomegalovirus (CMV) infection on
human immunodeficiency virus (HIV) disease progression were examined in
393 hemophilia patients with known dates of HIV seroconversion. Of the
cases, 191 (49%) had IgG antibody to CMV in their earliest stored sera
(median date, November 1983). CMV-seropositive subjects were one and a
half times more likely to develop AIDS, and they were also older than
CMV-negative subjects. Adjusted for age, CMV seropositivity was not
associated with the development of AIDS. In age-adjusted analyses,
CMV-seropositive subjects had a small, but statistically insignificant,
decrease in survival after HIV seroconversion. Older subjects were more
likely to CMV seroconvert by the time of their latest available serum
samples (P = .03). CMV seroconverters were five times more likely to
develop clinical CMV disease than were subjects initially CMV-positive
(P = .02). To avoid this source of serious morbidity, CMV-seronegative
hemophiliacs with HIV infection should not be exposed to cellular blood
products or body fluids from CMV-seropositive donors
Skin disease in haemophiliacs with and without antibodies to the human immunodeficiency virus (HIV): further evidence of altered disease behaviour in different risk groups?
- …