Genome-Wide Association Study of HIV-Related Lipoatrophy in Thai Patients: Association of a DLGAP1 Polymorphism with Fat Loss
| Autor: | Srisin Khusmith, Tatsuo Shioda, Tiphaine Oudot-Mellakh, Sumonmal Uttayamakul, Chariya Sangsajja, Emi E. Nakayama, Jean-François Delfraissy, Julien Guergnon, Sirirat Likanonsakul, Ioannis Theodorou, Pimrapat Tengtrakulcharoen |
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| Rok vydání: | 2015 |
| Předmět: |
Adult
Male medicine.medical_specialty Epidemiology Immunology HIV Infections Nerve Tissue Proteins Single-nucleotide polymorphism Genome-wide association study Biology Polymorphism Single Nucleotide Polymorphism (computer science) Virology Internal medicine Genotype medicine TaqMan Humans SNP Lipoatrophy Genetics HIV-Associated Lipodystrophy Syndrome Stavudine Middle Aged Thailand medicine.disease SAP90-PSD95 Associated Proteins Infectious Diseases Adipose Tissue Female Atrophy Genome-Wide Association Study medicine.drug |
| Zdroj: | AIDS Research and Human Retroviruses |
| ISSN: | 1931-8405 0889-2229 |
| DOI: | 10.1089/aid.2014.0266 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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