title: African mitochondrial DNA subhaplogroups and peripheral neuropathy during antiretroviral therapy.
abstract: Susceptibility to peripheral neuropathy during antiretroviral therapy with nucleoside reverse-transcriptase inhibitors was previously associated with a European mitochondrial DNA (mtDNA) haplogroup among non-Hispanic white persons. To determine whether nucleoside reverse-transcriptase inhibitor-associated peripheral neuropathy was related to mtDNA variation in non-Hispanic black persons, we sequenced mtDNA of participants from AIDS Clinical Trials Group study 384. Of 156 non-Hispanic black persons with genomic data, 51 (33%) developed peripheral neuropathy. In a multivariate model, African mtDNA subhaplogroup L1c was an independent predictor of peripheral neuropathy (odds ratio, 3.7 [95% confidence interval, 1.1-12.0]). An African mtDNA subhaplogroup is for the first time implicated in susceptibility to nucleoside reverse-transcriptase inhibitor-associated toxicity.
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, 345 24th Ave. North, Nashville, TN 37203, USA. todd.hulgan@vanderbilt.edu
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Canter
authors.forename: Gregory K
authors.initials: GK
authors.lastname: Robbins
authors.forename: Doug
authors.initials: D
authors.lastname: Selph
authors.forename: David B
authors.initials: DB
authors.lastname: Clifford
authors.forename: Asha R
authors.initials: AR
authors.lastname: Kallianpur
authors.forename: Robert
authors.initials: R
authors.lastname: Shafer
authors.forename: Shawn
authors.initials: S
authors.lastname: Levy
authors.forename: Deborah G
authors.initials: DG
authors.lastname: Murdock
authors.forename: Marylyn D
authors.initials: MD
authors.lastname: Ritchie
authors.forename: David W
authors.initials: DW
authors.lastname: Haas
authors.forename: Todd
authors.initials: T
authors.lastname: Hulgan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D044383:Black People; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008297:Male; D008875:Middle Aged; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000235:genetics*; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D017422:Sequence Analysis, DNA; D055815:Young Adult
chemical_list: D004272:DNA, Mitochondrial; D018894:Reverse Transcriptase Inhibitors
references.citation: Am J Hum Genet. 2003 Apr;72(4):804-11
references.pmid: 12618962
references.citation: Proc Natl Acad Sci U S A. 1994 Sep 13;91(19):8739-46
references.pmid: 8090716
references.citation: Clin Infect Dis. 2005 Jan 1;40(1):148-57
references.pmid: 15614705
references.citation: Lab Invest. 2001 Nov;81(11):1537-44
references.pmid: 11706061
references.citation: AIDS. 2005 Sep 2;19(13):1341-9
references.pmid: 16103764
references.citation: Forensic Sci Int. 2005 Mar 10;148(2-3):169-79
references.pmid: 15639612
references.citation: Comp Biochem Physiol B Biochem Mol Biol. 2005 Mar;140(3):497-503
references.pmid: 15694598
references.citation: Med Sci Sports Exerc. 2009 Jan;41(1):123-8
references.pmid: 19092698
references.citation: J Peripher Nerv Syst. 2001 Mar;6(1):14-20
references.pmid: 11293802
references.citation: Am J Hum Genet. 2002 May;70(5):1152-71
references.pmid: 11938495
references.citation: J Acquir Immune Defic Syndr. 2007 Jul 1;45(3):304-10
references.pmid: 17414931
references.citation: HIV Med. 2007 Sep;8(6):367-73
references.pmid: 17661844
references.citation: Hum Genet. 2003 Jan;112(1):29-33
references.pmid: 12483296
references.citation: N Engl J Med. 2003 Dec 11;349(24):2293-303
references.pmid: 14668455