title: Genome-Wide Association Study of HIV-Related Lipoatrophy in Thai Patients: Association of a DLGAP1 Polymorphism with Fat Loss.
abstract: HIV-related lipoatrophy (LA) is a major adverse drug effect among HIV patients receiving the antiretroviral drug stavudine (d4T) in Southeast Asia. Although the development of LA could be observed in almost all HIV patients administered d4T for extended periods, there is considerable variation in the duration required to develop LA within this patient population. This study aimed to identify host genetic polymorphisms affecting the rate of LA onset in Thai HIV patients. We performed a genome-wide association study of HIV-related LA among patients at the Bamrasnaradura Infectious Diseases Institute, Thailand. Genotypes of HIV patients who developed LA within 2 years of treatment were compared with those of patients who did not develop LA after at least 4 years of treatment (non-LA patients). Genotypes of 49 LA and 92 non-LA patients at 578,525 single nucleotide polymorphisms (SNPs) were determined by Illumina bead arrays. The TaqMan real-time PCR method was used in a replication study. Five SNPs in the bead arrays, which showed the lowest p values in a comparison of LA with non-LA patients, were further tested in independent and sex-matched subpopulations consisting of 95 LA and 95 non-LA patients. This replication study revealed a significant association of LA with an SNP (rs12964965) in the gene encoding the Disks Large Homolog-Associated Protein 1 (DLGAP1), even after the correction for five multiple comparisons. These results strongly suggested involvement of the DLGAP1 gene product in the development of LA in Thai HIV patients.
authors.affiliation: 1 Bamrasnaradura Infectious Diseases Institute , Department of Disease Control, Ministry of Public Health, Nonthaburi, Thailand .
authors.forename: Sumonmal
authors.initials: S
authors.lastname: Uttayamakul
authors.affiliation: 2 INSERM , U1135, CIMI, Plateforme génomique ANRS, Paris, France .
authors.forename: Tiphaine
authors.initials: T
authors.lastname: Oudot-Mellakh
authors.affiliation: 3 Research Institute for Microbial Diseases, Osaka University , Suita, Osaka, Japan .
authors.forename: Emi E
authors.initials: EE
authors.lastname: Nakayama
authors.affiliation: 4 Faculty of Medicine Siriraj Hospital, Mahidol University , Bangkok, Thailand .
authors.forename: Pimrapat
authors.initials: P
authors.lastname: Tengtrakulcharoen
authors.affiliation: 2 INSERM , U1135, CIMI, Plateforme génomique ANRS, Paris, France .
authors.forename: Julien
authors.initials: J
authors.lastname: Guergnon
authors.affiliation: 5 AP-HP, Hôpital Kremlin-Bicêtre , Internal Medicine Department, Le Kremlin-Bicêtre, France .|6 Faculty of Medicine Paris-Sud , Le Kremlin-Bicêtre, France .
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Delfraissy
authors.affiliation: 7 Faculty of Tropical Medicine, Mahidol University , Bangkok, Thailand .
authors.forename: Srisin
authors.initials: S
authors.lastname: Khusmith
authors.affiliation: 1 Bamrasnaradura Infectious Diseases Institute , Department of Disease Control, Ministry of Public Health, Nonthaburi, Thailand .
authors.forename: Chariya
authors.initials: C
authors.lastname: Sangsajja
authors.affiliation: 1 Bamrasnaradura Infectious Diseases Institute , Department of Disease Control, Ministry of Public Health, Nonthaburi, Thailand .
authors.forename: Sirirat
authors.initials: S
authors.lastname: Likanonsakul
authors.affiliation: 2 INSERM , U1135, CIMI, Plateforme génomique ANRS, Paris, France .|8 AP-HP, Hôpital Pitié-Salpêtrière , Département d'Immunologie, Paris, France .
authors.forename: Ioannis
authors.initials: I
authors.lastname: Theodorou
authors.affiliation: 3 Research Institute for Microbial Diseases, Osaka University , Suita, Osaka, Japan .
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Shioda
mesh_terms: D000273:Adipose Tissue / Q000473:pathology*; D000328:Adult; D001284:Atrophy / Q000139:chemically induced / Q000235:genetics*; D005260:Female; D055106:Genome-Wide Association Study; D015658:HIV Infections / Q000150:complications*; D039682:HIV-Associated Lipodystrophy Syndrome / Q000139:chemically induced / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D000074407:SAP90-PSD95 Associated Proteins; D013785:Thailand
chemical_list: C000614187:DLGAP1 protein, human; D009419:Nerve Tissue Proteins; D000074407:SAP90-PSD95 Associated Proteins