African mitochondrial DNA subhaplogroups and peripheral neuropathy during antiretroviral therapy.
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.
Canter
Jeffrey A
JA
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, 345 24th Ave. North, Nashville, TN 37203, USA. todd.hulgan@vanderbilt.edu
Robbins
Gregory K
GK
Selph
Doug
D
Clifford
David B
DB
Kallianpur
Asha R
AR
Shafer
Robert
R
Levy
Shawn
S
Murdock
Deborah G
DG
Ritchie
Marylyn D
MD
Haas
David W
DW
Hulgan
Todd
T
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
D004272:DNA, Mitochondrial; D018894:Reverse Transcriptase Inhibitors
Am J Hum Genet. 2003 Apr;72(4):804-11
12618962
Proc Natl Acad Sci U S A. 1994 Sep 13;91(19):8739-46
8090716
Clin Infect Dis. 2005 Jan 1;40(1):148-57
15614705
Lab Invest. 2001 Nov;81(11):1537-44
11706061
AIDS. 2005 Sep 2;19(13):1341-9
16103764
Forensic Sci Int. 2005 Mar 10;148(2-3):169-79
15639612
Comp Biochem Physiol B Biochem Mol Biol. 2005 Mar;140(3):497-503
15694598
Med Sci Sports Exerc. 2009 Jan;41(1):123-8
19092698
J Peripher Nerv Syst. 2001 Mar;6(1):14-20
11293802
Am J Hum Genet. 2002 May;70(5):1152-71
11938495
J Acquir Immune Defic Syndr. 2007 Jul 1;45(3):304-10
17414931
HIV Med. 2007 Sep;8(6):367-73
17661844
Hum Genet. 2003 Jan;112(1):29-33
12483296
N Engl J Med. 2003 Dec 11;349(24):2293-303
14668455