Mitochondrial DNA variation and HIV-associated sensory neuropathy in CHARTER

Emily R. Holzinger, Todd Hulgan, Ronald J. Ellis, David C. Samuels, Marylyn D. Ritchie, David W. Haas, Asha R. Kallianpur, Cinnamon S. Bloss, David B. Clifford, Ann C. Collier, Benjamin Gelman, Christina M. Marra, Justin C. McArthur, J. Allen McCutchan, Susan Morgello, David M. Simpson, Donald R. Franklin, Debralee Rosario, Doug Selph, Scott Letendre & 1 others Igor Grant

Research output: Contribution to journalArticle

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Abstract

HIV-associated sensory neuropathy remains an important complication of combination antiretroviral therapy and HIV infection. Mitochondrial DNA haplogroups and single nucleotide polymorphisms (SNPs) have previously been associated with symptomatic neuropathy in clinical trial participants. We examined associations between mitochondrial DNA variation and HIV-associated sensory neuropathy in CNS HIV Antiretroviral Therapy Effects Research (CHARTER). CHARTER is a USA-based longitudinal observational study of HIV-infected adults who underwent a structured interview and standardized examination. HIV-associated sensory neuropathy was determined by trained examiners as ≥1 sign (diminished vibratory and sharp-dull discrimination or ankle reflexes) bilaterally. Mitochondrial DNA sequencing was performed and haplogroups were assigned by published algorithms. Multivariable logistic regression of associations between mitochondrial DNA SNPs, haplogroups, and HIV-associated sensory neuropathy were performed. In analyses of associations of each mitochondrial DNA SNP with HIV-associated sensory neuropathy, the two most significant SNPs were at positions A12810G [odds ratio (95 % confidence interval) = 0.27 (0.11-0.65); p = 0.004] and T489C [odds ratio (95 % confidence interval) = 0.41 (0.21-0.80); p = 0.009]. These synonymous changes are known to define African haplogroup L1c and European haplogroup J, respectively. Both haplogroups were associated with decreased prevalence of HIV-associated sensory neuropathy compared with all other haplogroups [odds ratio (95 % confidence interval) = 0.29 (0.12-0.71); p = 0.007 and odds ratio (95 % confidence interval) = 0.42 (0.18-1.0); p = 0.05, respectively]. In conclusion, in this cohort of mostly combination antiretroviral therapy-treated subjects, two common mitochondrial DNA SNPs and their corresponding haplogroups were associated with a markedly decreased prevalence of HIV-associated sensory neuropathy.

Original languageEnglish (US)
Pages (from-to)511-520
Number of pages10
JournalJournal of NeuroVirology
Volume18
Issue number6
DOIs
StatePublished - Dec 2012

Fingerprint

Mitochondrial DNA
HIV
Research
Single Nucleotide Polymorphism
Odds Ratio
Confidence Intervals
Therapeutics
DNA Sequence Analysis
Ankle
HIV Infections
Observational Studies
Longitudinal Studies
Reflex
Logistic Models
Clinical Trials
Interviews

Keywords

  • Genetics
  • HIV-related neurological diseases
  • Mitochondria
  • Peripheral neuropathy

ASJC Scopus subject areas

  • Virology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Neurology

Cite this

Holzinger, E. R., Hulgan, T., Ellis, R. J., Samuels, D. C., Ritchie, M. D., Haas, D. W., ... Grant, I. (2012). Mitochondrial DNA variation and HIV-associated sensory neuropathy in CHARTER. Journal of NeuroVirology, 18(6), 511-520. https://doi.org/10.1007/s13365-012-0133-y

Mitochondrial DNA variation and HIV-associated sensory neuropathy in CHARTER. / Holzinger, Emily R.; Hulgan, Todd; Ellis, Ronald J.; Samuels, David C.; Ritchie, Marylyn D.; Haas, David W.; Kallianpur, Asha R.; Bloss, Cinnamon S.; Clifford, David B.; Collier, Ann C.; Gelman, Benjamin; Marra, Christina M.; McArthur, Justin C.; McCutchan, J. Allen; Morgello, Susan; Simpson, David M.; Franklin, Donald R.; Rosario, Debralee; Selph, Doug; Letendre, Scott; Grant, Igor.

In: Journal of NeuroVirology, Vol. 18, No. 6, 12.2012, p. 511-520.

Research output: Contribution to journalArticle

Holzinger, ER, Hulgan, T, Ellis, RJ, Samuels, DC, Ritchie, MD, Haas, DW, Kallianpur, AR, Bloss, CS, Clifford, DB, Collier, AC, Gelman, B, Marra, CM, McArthur, JC, McCutchan, JA, Morgello, S, Simpson, DM, Franklin, DR, Rosario, D, Selph, D, Letendre, S & Grant, I 2012, 'Mitochondrial DNA variation and HIV-associated sensory neuropathy in CHARTER', Journal of NeuroVirology, vol. 18, no. 6, pp. 511-520. https://doi.org/10.1007/s13365-012-0133-y
Holzinger ER, Hulgan T, Ellis RJ, Samuels DC, Ritchie MD, Haas DW et al. Mitochondrial DNA variation and HIV-associated sensory neuropathy in CHARTER. Journal of NeuroVirology. 2012 Dec;18(6):511-520. https://doi.org/10.1007/s13365-012-0133-y
Holzinger, Emily R. ; Hulgan, Todd ; Ellis, Ronald J. ; Samuels, David C. ; Ritchie, Marylyn D. ; Haas, David W. ; Kallianpur, Asha R. ; Bloss, Cinnamon S. ; Clifford, David B. ; Collier, Ann C. ; Gelman, Benjamin ; Marra, Christina M. ; McArthur, Justin C. ; McCutchan, J. Allen ; Morgello, Susan ; Simpson, David M. ; Franklin, Donald R. ; Rosario, Debralee ; Selph, Doug ; Letendre, Scott ; Grant, Igor. / Mitochondrial DNA variation and HIV-associated sensory neuropathy in CHARTER. In: Journal of NeuroVirology. 2012 ; Vol. 18, No. 6. pp. 511-520.
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AU - Haas, David W.

AU - Kallianpur, Asha R.

AU - Bloss, Cinnamon S.

AU - Clifford, David B.

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AU - McArthur, Justin C.

AU - McCutchan, J. Allen

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AU - Letendre, Scott

AU - Grant, Igor

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N2 - HIV-associated sensory neuropathy remains an important complication of combination antiretroviral therapy and HIV infection. Mitochondrial DNA haplogroups and single nucleotide polymorphisms (SNPs) have previously been associated with symptomatic neuropathy in clinical trial participants. We examined associations between mitochondrial DNA variation and HIV-associated sensory neuropathy in CNS HIV Antiretroviral Therapy Effects Research (CHARTER). CHARTER is a USA-based longitudinal observational study of HIV-infected adults who underwent a structured interview and standardized examination. HIV-associated sensory neuropathy was determined by trained examiners as ≥1 sign (diminished vibratory and sharp-dull discrimination or ankle reflexes) bilaterally. Mitochondrial DNA sequencing was performed and haplogroups were assigned by published algorithms. Multivariable logistic regression of associations between mitochondrial DNA SNPs, haplogroups, and HIV-associated sensory neuropathy were performed. In analyses of associations of each mitochondrial DNA SNP with HIV-associated sensory neuropathy, the two most significant SNPs were at positions A12810G [odds ratio (95 % confidence interval) = 0.27 (0.11-0.65); p = 0.004] and T489C [odds ratio (95 % confidence interval) = 0.41 (0.21-0.80); p = 0.009]. These synonymous changes are known to define African haplogroup L1c and European haplogroup J, respectively. Both haplogroups were associated with decreased prevalence of HIV-associated sensory neuropathy compared with all other haplogroups [odds ratio (95 % confidence interval) = 0.29 (0.12-0.71); p = 0.007 and odds ratio (95 % confidence interval) = 0.42 (0.18-1.0); p = 0.05, respectively]. In conclusion, in this cohort of mostly combination antiretroviral therapy-treated subjects, two common mitochondrial DNA SNPs and their corresponding haplogroups were associated with a markedly decreased prevalence of HIV-associated sensory neuropathy.

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