Mitochondrial DNA variation and HIV-associated sensory neuropathy in CHARTER.
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.
Vanderbilt University, Nashville, TN 37232, USA.
Emily R
ER
Holzinger
Todd
T
Hulgan
Ronald J
RJ
Ellis
David C
DC
Samuels
Marylyn D
MD
Ritchie
David W
DW
Haas
Asha R
AR
Kallianpur
Cinnamon S
CS
Bloss
David B
DB
Clifford
Ann C
AC
Collier
Benjamin B
BB
Gelman
Christina M
CM
Marra
Justin C
JC
McArthur
J Allen
JA
McCutchan
Susan
S
Morgello
David M
DM
Simpson
Donald R
DR
Franklin
Debralee
D
Rosario
Doug
D
Selph
Scott
S
Letendre
Igor
I
Grant
D000328:Adult; D044383:Black People; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D015497:HIV-1; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011115:Polyneuropathies / Q000188:drug therapy / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D011446:Prospective Studies; D044465:White People
D004272:DNA, Mitochondrial