title: RXRγ gene variants are associated with HIV lipodystrophy.
abstract: HIV lipodystrophy (HIVLD), associated with combination antiretroviral therapy (cART), leads to metabolic and cardiovascular diseases. Nuclear receptors play a central role in lipid homoeostasis and drug disposition; their genetic variants may predispose an individual to the development of HIVLD. DNA samples obtained from cART-treated HIV-positive patients with (HIVLD+; 124) and without (HIVLD-; 56) HIVLD were genotyped for 77 single nucleotide polymorphisms in nine nuclear receptor genes. Statistical analysis was carried out using Haploview software and by logistic regression. Three single nucleotide polymorphisms in RXRγ (rs2134095, rs113471, rs2194899) and its haplotypes (HIVLD+, 54%; HIVLD-, 40.6%; P=0.02) showed significant association with HIVLD. Multivariate analysis identified time since diagnosis (P=0.001) and carriage of the RXRγ haplotype (P=0.02) to be independently associated with HIVLD. Genetic variation in RXRγ, a common binding partner of nuclear receptors that modulate lipid homoeostasis and drug disposition, may contribute to the development of HIVLD in cART-treated HIV patients. These results need replication in other cohorts.
authors.affiliation: NIHR Biomedical Research Centre, Royal Liverpool Hospital, Liverpool, UK. sudeepp@liv.ac.uk
authors.forename: Sudeep P
authors.initials: SP
authors.lastname: Pushpakom
authors.forename: Andrew
authors.initials: A
authors.lastname: Owen
authors.forename: David J
authors.initials: DJ
authors.lastname: Back
authors.forename: Munir
authors.initials: M
authors.lastname: Pirmohamed
mesh_terms: D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D015331:Cohort Studies; D014644:Genetic Variation; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics; D039682:HIV-Associated Lipodystrophy Syndrome / Q000139:chemically induced / Q000188:drug therapy / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D016015:Logistic Models; D020641:Polymorphism, Single Nucleotide; D047491:Retinoid X Receptor gamma / Q000235:genetics* / Q000378:metabolism
chemical_list: D019380:Anti-HIV Agents; D047491:Retinoid X Receptor gamma