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APOC3 Gene Polymorphism and Antiretroviral Therapy-Induced Dyslipidemia in HIV-Infected Children
AIDS Research and Human Retroviruses ( IF 1.5 ) Pub Date : 2021-02-05 , DOI: 10.1089/aid.2020.0082
Ramalingam Srinivasan 1 , Chandrasekaran Padmapriyadarsini 1 , Karunaianantham Ramesh 1 , G N Sanjeeva 2 , Devarajulu Reddy 1 , Elumalai Suresh 3 , Ramesh Kumar 1 , Pattabiraman Sathyamoorthy 1 , Soumya Swaminathan 4 , Anita Shet 5
Affiliation  

Children exposed to antiretroviral therapy (ART) are at risk of developing metabolic complications. The association between gene polymorphisms and the development of dyslipidemia in children post ART initiation was studied. Children initiating first-line ART were followed for 2 years at the National Institute for Research in Tuberculosis (Chennai, India), and St. John's Medical College Hospital (Bangalore, India). Clinical examination and fasting serum lipid profiles were measured every 6 months. Participants were genotyped for the polymorphisms in the APOC3 gene (rs2854116; rs2854117, and rs5128). Changes in lipid levels from baseline to months 6, 12, and 24, and the difference between the various genotype variants were analyzed using a modified analysis of variance test. Study enrolled 393 ART-naive HIV-infected children (mean age: 7.6 ± 3 years, mean weight: 18 ± 6) of whom 289 (75%) were started on nevirapine (NVP)-based ART and the remaining 96 (25%) were started on efavirenz-based ART. Only children carrying the GG allele of rs5128 genotype showed a decrease in CD4% and serum triglycerides pre-ART. An increasing trend of total cholesterol, high-density lipoprotein cholesterol (HDL-c), and low-density lipoprotein cholesterol were seen at 6 months in both EFZ and NVP groups, which subsequently stabilized by 12 months irrespective of genotype variants. Genotype variants of APOC3 (rs2854116 and rs2854117 polymorphism) did not show significant changes in serum lipid levels after 24 months of ART, whereas rs5128 polymorphism with “G” allele showed an association with HDL-c levels when on NVP-based ART. Our results suggest that ART plays a major role in normalizing lipid levels in HIV-infected children and APOC3 polymorphisms may not play a significant role in ART-induced dyslipidemia.

中文翻译:

HIV感染儿童的APOC3基因多态性和抗逆转录病毒治疗引起的血脂异常

接受抗逆转录病毒治疗 (ART) 的儿童有发生代谢并发症的风险。研究了 ART 开始后基因多态性与儿童血脂异常发展之间的关联。在国家结核病研究所(印度钦奈)和圣约翰医学院医院(印度班加罗尔)对启动一线 ART 的儿童进行了 2 年的随访。每 6 个月测量一次临床检查和空腹血脂谱。参与者对 APOC3 基因(rs2854116;rs2854117 和 rs5128)中的多态性进行基因分型。使用改进的方差分析分析分析从基线到第 6、12 和 24 个月的脂质水平变化,以及各种基因型变体之间的差异。研究招募了 393 名未接受过 ART 的 HIV 感染儿童(平均年龄:7. 6 ± 3 年,平均体重:18 ± 6) 其中 289 (75%) 人开始接受基于奈韦拉平 (NVP) 的抗逆转录病毒疗法,其余 96 人 (25%) 开始接受基于依非韦伦的抗逆转录病毒疗法。只有携带 rs5128 基因型 GG 等位基因的儿童在 ART 前表现出 CD4% 和血清甘油三酯降低。在 6 个月时,EFZ 和 NVP 组的总胆固醇、高密度脂蛋白胆固醇 (HDL-c) 和低密度脂蛋白胆固醇呈上升趋势,随后稳定了 12 个月,而与基因型变异无关。APOC3 的基因型变体(rs2854116 和 rs2854117 多态性)在 ART 24 个月后没有显示出血清脂质水平的显着变化,而具有“G”等位基因的 rs5128 多态性在基于 NVP 的 ART 中显示与 HDL-c 水平相关。
更新日期:2021-02-10
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