Mitochondrial DNA variation and HIV-associated sensory neuropathy in CHARTER

Journal of NeuroVirology - Tập 18 - Trang 511-520 - 2012
Emily R. Holzinger1, Todd Hulgan1, Ronald J. Ellis2, David C. Samuels1, Marylyn D. Ritchie3, David W. Haas1, Asha R. Kallianpur1, Cinnamon S. Bloss4, David B. Clifford5, Ann C. Collier6, Benjamin B. Gelman7, Christina M. Marra6, Justin C. McArthur8, J. Allen McCutchan2, Susan Morgello9, David M. Simpson9, Donald R. Franklin2, Debralee Rosario2, Doug Selph1, Scott Letendre10, Igor Grant2
1Vanderbilt University, Nashville, USA
2University of California San Diego, San Diego, USA
3The Pennsylvania State University, University Park, USA
4Scripps Research Institute, La Jolla, USA
5Washington University, St. Louis, USA
6University of Washington, Seattle, USA
7University of Texas Medical Branch, Galveston, USA
8Johns Hopkins University, Baltimore, USA
9Mount Sinai School of Medicine, New York, USA
10University of California-San Diego, San Diego, USA

Tóm tắt

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.

Tài liệu tham khảo

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