Genome-Wide Association Study of HIV-Related Lipoatrophy in Thai Patients: Association of a DLGAP1 Polymorphism with Fat Loss.
Genome-Wide Association Study of HIV-Related Lipoatrophy in Thai Patients: Association of a DLGAP1 Polymorphism with Fat Loss.
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泰国患者HIV相关脂肪哲学的全基因组关联研究：DLGAP1多态性与脂肪损失的关联。
DOI：
10.1089/aid.2014.0266
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发表时间：
2015-08
影响因子：
1.5
通讯作者：
Shioda T
中科院分区：
文献类型：
--
作者：
Uttayamakul S;Oudot-Mellakh T;Nakayama EE;Tengtrakulcharoen P;Guergnon J;Delfraissy JF;Khusmith S;Sangsajja C;Likanonsakul S;Theodorou I;Shioda T
HIV相关脂肪萎缩（LA）是东南亚接受抗逆转录病毒药物司他夫定（d4T）治疗的HIV患者的主要不良反应。尽管在几乎所有长期服用d4T的HIV患者中都可以观察到LA的发展，但在这些患者群体中，发生LA所需的持续时间存在相当大的差异。本研究旨在确定影响泰国HIV患者LA发病率的宿主遗传多态性。我们在泰国Bamrasnaradura传染病研究所的患者中进行了hiv相关LA的全基因组关联研究。将治疗2年内发生LA的HIV患者的基因型与治疗至少4年后未发生LA的患者（非LA患者）的基因型进行比较。采用Illumina头阵列技术对49例LA患者和92例非LA患者的578,525个单核苷酸多态性（snp）进行基因型分析。重复实验采用TaqMan实时PCR法。在由95名LA患者和95名非LA患者组成的独立和性别匹配的亚群中，进一步测试了头阵列中的5个snp，这些snp在LA患者与非LA患者的比较中显示出最低的p值。这项重复性研究揭示了LA与编码磁盘大同源相关蛋白1 （DLGAP1）基因的SNP （rs12964965）之间的显著关联，即使在进行了五次多重比较校正后也是如此。这些结果强烈提示DLGAP1基因产物参与了泰国HIV患者LA的发展。
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.