Mitochondrial DNA variation and changes in adiponectin and endothelial function in HIV-infected adults after antiretroviral therapy initiation.

TitleMitochondrial DNA variation and changes in adiponectin and endothelial function in HIV-infected adults after antiretroviral therapy initiation.
Publication TypeJournal Article
Year of Publication2013
AuthorsHulgan T, Stein JH, Cotter BR, Murdock DG, Ritchie MD, Dubé MP, Gerschenson M, Haas DW, Torriani FJ
Corporate AuthorsAids Clinical Trials Group A5152s And Dacs 252 Study Teams
JournalAIDS Res Hum Retroviruses
Volume29
Issue10
Pagination1293-9
Date Published2013 Oct
ISSN1931-8405
KeywordsAdiponectin, Adult, Anti-Retroviral Agents, Antiretroviral Therapy, Highly Active, Dilatation, Pathologic, DNA, Mitochondrial, Female, HIV Infections, Humans, Male, Polymorphism, Single Nucleotide
Abstract

Studies in persons of European descent have suggested that mitochondrial DNA (mtDNA) haplogroups influence antiretroviral therapy (ART) toxicity. We explored associations between mtDNA variants and changes in endothelial function and biomarkers among non-Hispanic white, ART-naive subjects starting ART. A5152s was a substudy of A5142, a randomized trial of initial class-sparing ART regimens that included efavirenz or lopinavir/ritonavir with nucleoside reverse transcriptase inhibitors (NRTIs), or both without NRTIs. Brachial artery flow-mediated dilation (FMD) and cardiovascular biomarker assessments were performed at baseline and at weeks 4 and 24. Ten haplogroup-defining mtDNA polymorphisms were determined. FMD and biomarker changes from baseline to week 24 by mtDNA variant were assessed using Wilcoxon rank-sum tests. Thirty-nine non-Hispanic white participants had DNA and 24-week data. The nonsynonymous m.10398A>G mtDNA polymorphism (N=8) was associated with higher median baseline adiponectin (5.0 vs. 4.2 μg/ml; p=0.003), greater absolute (-1.9 vs. -0.2 μg/ml) and relative (-33% vs. -3%) adiponectin decreases (p<0.001 for both), and lower week 24 brachial artery FMD (3.6% vs. 5.4%; p=0.04). Individual mtDNA haplogroups, including haplogroups H (N=13) and U (N=6), were not associated with adiponectin or FMD changes. In this small pilot study, adiponectin and brachial artery FMD on ART differed in non-Hispanic whites with a nonsynonymous mtDNA variant associated with several human diseases. These preliminary findings support the hypothesis that mtDNA variation influences metabolic ART effects. Validation studies in larger populations and in different racial/ethnic groups that include m.10398G carriers are needed.

DOI10.1089/aid.2013.0079
Alternate JournalAIDS Res. Hum. Retroviruses
PubMed ID23944767
PubMed Central IDPMC3785797
Grant ListAI 060354 / AI / NIAID NIH HHS / United States
AI 064086 / AI / NIAID NIH HHS / United States
AI 068634 / AI / NIAID NIH HHS / United States
AI 069411 / AI / NIAID NIH HHS / United States
AI 069418 / AI / NIAID NIH HHS / United States
AI 069419 / AI / NIAID NIH HHS / United States
AI 069423 / AI / NIAID NIH HHS / United States
AI 069424 / AI / NIAID NIH HHS / United States
AI 069434 / AI / NIAID NIH HHS / United States
AI 069439 / AI / NIAID NIH HHS / United States
AI 069447 / AI / NIAID NIH HHS / United States
AI 069450 / AI / NIAID NIH HHS / United States
AI 069452 / AI / NIAID NIH HHS / United States
AI 069465 / AI / NIAID NIH HHS / United States
AI 069470 / AI / NIAID NIH HHS / United States
AI 069471 / AI / NIAID NIH HHS / United States
AI 069472 / AI / NIAID NIH HHS / United States
AI 069474 / AI / NIAID NIH HHS / United States
AI 069477 / AI / NIAID NIH HHS / United States
AI 069484 / AI / NIAID NIH HHS / United States
AI 069494 / AI / NIAID NIH HHS / United States
AI 069495 / AI / NIAID NIH HHS / United States
AI 069501 / AI / NIAID NIH HHS / United States
AI 069502 / AI / NIAID NIH HHS / United States
AI 069513 / AI / NIAID NIH HHS / United States
AI 069532 / AI / NIAID NIH HHS / United States
AI 069556 / AI / NIAID NIH HHS / United States
AI 25859 / AI / NIAID NIH HHS / United States
AI 25915 / AI / NIAID NIH HHS / United States
AI 27661 / AI / NIAID NIH HHS / United States
AI 27673 / AI / NIAID NIH HHS / United States
AI 32782 / AI / NIAID NIH HHS / United States
AI 32783 / AI / NIAID NIH HHS / United States
AI 34853 / AI / NIAID NIH HHS / United States
AI 36214 / AI / NIAID NIH HHS / United States
AI 38858 / AI / NIAID NIH HHS / United States
AI 45008 / AI / NIAID NIH HHS / United States
AI 46370 / AI / NIAID NIH HHS / United States
AI 46376 / AI / NIAID NIH HHS / United States
AI 46381 / AI / NIAID NIH HHS / United States
AI 50410 / AI / NIAID NIH HHS / United States
AI 60484 / AI / NIAID NIH HHS / United States
AI 64086 / AI / NIAID NIH HHS / United States
AI 69432 / AI / NIAID NIH HHS / United States
AI 77505 / AI / NIAID NIH HHS / United States
AI068636 / AI / NIAID NIH HHS / United States
AI069432 / AI / NIAID NIH HHS / United States
DA12121 / DA / NIDA NIH HHS / United States
G12 MD007601 / MD / NIMHD NIH HHS / United States
GM 103341 / GM / NIGMS NIH HHS / United States
MD 000173 / MD / NIMHD NIH HHS / United States
MD 007601 / MD / NIMHD NIH HHS / United States
RR 00032 / RR / NCRR NIH HHS / United States
RR 00039 / RR / NCRR NIH HHS / United States
RR 00044 / RR / NCRR NIH HHS / United States
RR 00046 / RR / NCRR NIH HHS / United States
RR 00047 / RR / NCRR NIH HHS / United States
RR 00051 / RR / NCRR NIH HHS / United States
RR 00052 / RR / NCRR NIH HHS / United States
RR 00075 / RR / NCRR NIH HHS / United States
RR 00096 / RR / NCRR NIH HHS / United States
RR 02635 / RR / NCRR NIH HHS / United States
RR 16176 / RR / NCRR NIH HHS / United States
U01AI068636 / AI / NIAID NIH HHS / United States
UL1 TR000454 / TR / NCATS NIH HHS / United States
UL1 TR001082 / TR / NCATS NIH HHS / United States
UL1TR000445 / TR / NCATS NIH HHS / United States
UM1 AI069423 / AI / NIAID NIH HHS / United States
UM1 AI069432 / AI / NIAID NIH HHS / United States
UM1 AI069471 / AI / NIAID NIH HHS / United States