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

Todd Hulgan, James H. Stein, Bruno R. Cotter, Deborah G. Murdock, Marylyn D. Ritchie, Michael P. Dube, Mariana Gerschenson, David W. Haas, Francesca J. Torriani

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1293-1299
Number of pages7
JournalAIDS Research and Human Retroviruses
Volume29
Issue number10
DOIs
StatePublished - Oct 1 2013

Fingerprint

Adiponectin
Mitochondrial DNA
HIV
Dilatation
Brachial Artery
Reverse Transcriptase Inhibitors
Biomarkers
efavirenz
Therapeutics
Nonparametric Statistics
Nucleosides
Lopinavir
Ritonavir
Validation Studies
Ethnic Groups
DNA
Population

All Science Journal Classification (ASJC) codes

  • Immunology
  • Virology
  • Infectious Diseases

Cite this

Hulgan, Todd ; Stein, James H. ; Cotter, Bruno R. ; Murdock, Deborah G. ; Ritchie, Marylyn D. ; Dube, Michael P. ; Gerschenson, Mariana ; Haas, David W. ; Torriani, Francesca J. / Mitochondrial DNA variation and changes in adiponectin and endothelial function in HIV-infected adults after antiretroviral therapy initiation. In: AIDS Research and Human Retroviruses. 2013 ; Vol. 29, No. 10. pp. 1293-1299.
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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.",
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Hulgan, T, Stein, JH, Cotter, BR, Murdock, DG, Ritchie, MD, Dube, MP, Gerschenson, M, Haas, DW & Torriani, FJ 2013, 'Mitochondrial DNA variation and changes in adiponectin and endothelial function in HIV-infected adults after antiretroviral therapy initiation', AIDS Research and Human Retroviruses, vol. 29, no. 10, pp. 1293-1299. https://doi.org/10.1089/aid.2013.0079

Mitochondrial DNA variation and changes in adiponectin and endothelial function in HIV-infected adults after antiretroviral therapy initiation. / Hulgan, Todd; Stein, James H.; Cotter, Bruno R.; Murdock, Deborah G.; Ritchie, Marylyn D.; Dube, Michael P.; Gerschenson, Mariana; Haas, David W.; Torriani, Francesca J.

In: AIDS Research and Human Retroviruses, Vol. 29, No. 10, 01.10.2013, p. 1293-1299.

Research output: Contribution to journalArticle

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T1 - Mitochondrial DNA variation and changes in adiponectin and endothelial function in HIV-infected adults after antiretroviral therapy initiation

AU - Hulgan, Todd

AU - Stein, James H.

AU - Cotter, Bruno R.

AU - Murdock, Deborah G.

AU - Ritchie, Marylyn D.

AU - Dube, Michael P.

AU - Gerschenson, Mariana

AU - Haas, David W.

AU - Torriani, Francesca J.

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N2 - 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.

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