Vanderbilt University, Nashville, Tennessee, USA.
AIDS. 2011 Jan 2;25(1):37-47. doi: 10.1097/QAD.0b013e32833f9d02.
Mitochondrial DNA (mtDNA) influences metabolic diseases and perhaps antiretroviral therapy (ART) complications. We explored associations between European mtDNA haplogroups and metabolic changes among A5142 participants.
Seven hundred and fifty-seven ART-naive patients were randomized to one of three class-sparing ART regimens including efavirenz and/or lopinavir/ritonavir with or without nucleoside reverse transcriptase inhibitors (NRTIs). Nonrandomized NRTIs included stavudine, tenofovir, or zidovudine, each with lamivudine. Fasting lipid profiles and whole-body dual-energy X-ray absorptiometry (DEXA) were performed. Nine European mtDNA haplogroups were determined for 231 self-identified non-Hispanic white individuals. Metabolic changes from baseline to 96 weeks were analyzed by haplogroup.
Median age was 39 years, 9% were women, and 37, 32, and 30 were randomized to NRTI-containing regimens with either efavirenz or lopinavir/ritonavir, and an NRTI-sparing regimen, respectively. Among NRTI-containing regimens, 51% included zidovudine, 28% tenofovir, and 21% stavudine. Compared with other haplogroups, mtDNA haplogroup I (N = 10) had higher baseline non-HDL cholesterol [160 mg/dl (interquartile range 137-171) vs. 120 mg/dl (104-136); P = 0.005], a decrease in non-HDL cholesterol over 96 weeks [-14% (-20 to 6) vs. +25% (8 to 51); P < 0.001], tended to have more baseline extremity fat, and had more extremity fat loss by DEXA [-13% (-13 to 12) vs. +9% (-13 to 26); P = 0.08] and lipoatrophy (50 vs. 20%; P = 0.04). Haplogroup W (N = 5; all randomized to NRTI-sparing regimens) had the greatest increase in extremity fat [+35.5% (26.8 to 54.9); P = 0.02].
Lipids and extremity fat were associated with European mtDNA haplogroups in this HIV-infected population. These preliminary results suggest that mitochondrial genomics may influence metabolic parameters before and during ART.
线粒体 DNA（mtDNA）影响代谢疾病，或许还影响抗逆转录病毒治疗（ART）的并发症。我们探究了 A5142 参与者中欧洲 mtDNA 单倍群与代谢变化之间的关联。
757 名未接受过 ART 的患者被随机分配到三种节省药物的 ART 方案之一，这些方案包括依非韦伦和/或洛匹那韦/利托那韦，联合或不联合核苷类逆转录酶抑制剂（NRTIs）。非随机 NRTIs 包括司他夫定、替诺福韦或齐多夫定，每种药物均联合拉米夫定。进行空腹血脂谱和全身双能 X 射线吸收法（DEXA）检测。对 231 名自我认定的非西班牙裔白人个体确定了 9 种欧洲 mtDNA 单倍群。通过单倍群分析了从基线到 96 周的代谢变化。
中位年龄为 39 岁，9%为女性，分别有 37%、32%和 30%随机分配到包含依非韦伦或洛匹那韦/利托那韦的 NRTI 方案和 NRTI 节省方案。在包含 NRTI 的方案中，51%包含齐多夫定，28%包含替诺福韦，21%包含司他夫定。与其他单倍群相比，mtDNA 单倍群 I（N=10）基线时非高密度脂蛋白胆固醇更高[160mg/dl（四分位间距 137-171）vs. 120mg/dl（104-136）；P=0.005]，96 周时非高密度脂蛋白胆固醇降低[14%（-20 至 6）vs. +25%（8 至 51）；P<0.001]，基线时四肢脂肪更多，DEXA 检查时四肢脂肪减少更多[-13%（-13 至 12）vs. +9%（-13 至 26）；P=0.08]，脂肪减少（50% vs. 20%；P=0.04）。单倍群 W（N=5；均随机分配到 NRTI 节省方案）四肢脂肪增加最多[+35.5%（26.8 至 54.9）；P=0.02]。
在该 HIV 感染人群中，脂质和四肢脂肪与欧洲 mtDNA 单倍群相关。这些初步结果提示线粒体基因组学可能在接受 ART 之前和期间影响代谢参数。
