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Mitochondrial DNA subhaplogroups L0a2 and L2a modify susceptibility to peripheral neuropathy in malawian adults on stavudine containing highly active antiretroviral therapy.
J Acquir Immune Defic Syndr. 2013 Aug 15; 63(5):647-52.JA

Abstract

BACKGROUND

Peripheral neuropathy (PN) is one of the main toxicities associated with stavudine. Genetic variants in mitochondrial DNA (mtDNA) haplogroups have been associated with increased risk of developing PN in European non-Hispanic and black patients on stavudine containing antiretroviral therapy (ART). We investigated mtDNA haplogroups and their role in susceptibility to stavudine-induced peripheral in Malawian patients on ART.

METHOD

Two hundred and fifteen adults on stavudine containing regimens were recruited from the ART clinic at Queen Elizabeth Central Hospital, Blantyre, into a cross-sectional study to investigate the effects of genetic variants in mtDNA of individuals in relation to response to treatment. Patients were categorized according to whether or not they had developed PN after a minimum of 6 months on stavudine containing ART. Whole mtDNA coding regions of each patient were sequenced, and CD4 count, viral load, and creatinine were determined. The mtDNA variation was correlated with clinical characteristics.

RESULTS

Fifty-three (25%) of the participants developed PN after starting stavudine containing ART. Mitochondrial DNA subhaplogroup L0a2 was independently associated with increased risk of PN in a multivariate model (odds ratio, 2.23; 95% confidence interval, 1.14 to 4.39; P = 0.019), and subhaplogroup L2a was independently associated with reduced risk of PN (odds ratio, 0.39; 95% confidence interval, 0.16 to 0.94; P = 0.036).

CONCLUSIONS

Genetic variation in mtDNA confers differential risk of developing PN in patients on stavudine containing ART among Malawians.

Authors+Show Affiliations

*Division of Human Genetics, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; and †Department of Pathology, ‡Department of Medicine, and §Malawi-Liverpool Wellcome Trust Clinical Research Programme, College of Medicine, University of Malawi, Malawi.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23614993

Citation

Kampira, Elizabeth, et al. "Mitochondrial DNA Subhaplogroups L0a2 and L2a Modify Susceptibility to Peripheral Neuropathy in Malawian Adults On Stavudine Containing Highly Active Antiretroviral Therapy." Journal of Acquired Immune Deficiency Syndromes (1999), vol. 63, no. 5, 2013, pp. 647-52.
Kampira E, Kumwenda J, van Oosterhout JJ, et al. Mitochondrial DNA subhaplogroups L0a2 and L2a modify susceptibility to peripheral neuropathy in malawian adults on stavudine containing highly active antiretroviral therapy. J Acquir Immune Defic Syndr. 2013;63(5):647-52.
Kampira, E., Kumwenda, J., van Oosterhout, J. J., & Dandara, C. (2013). Mitochondrial DNA subhaplogroups L0a2 and L2a modify susceptibility to peripheral neuropathy in malawian adults on stavudine containing highly active antiretroviral therapy. Journal of Acquired Immune Deficiency Syndromes (1999), 63(5), 647-52. https://doi.org/10.1097/QAI.0b013e3182968ea5
Kampira E, et al. Mitochondrial DNA Subhaplogroups L0a2 and L2a Modify Susceptibility to Peripheral Neuropathy in Malawian Adults On Stavudine Containing Highly Active Antiretroviral Therapy. J Acquir Immune Defic Syndr. 2013 Aug 15;63(5):647-52. PubMed PMID: 23614993.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mitochondrial DNA subhaplogroups L0a2 and L2a modify susceptibility to peripheral neuropathy in malawian adults on stavudine containing highly active antiretroviral therapy. AU - Kampira,Elizabeth, AU - Kumwenda,Johnstone, AU - van Oosterhout,Joep J, AU - Dandara,Collet, PY - 2013/4/26/entrez PY - 2013/4/26/pubmed PY - 2013/11/13/medline SP - 647 EP - 52 JF - Journal of acquired immune deficiency syndromes (1999) JO - J Acquir Immune Defic Syndr VL - 63 IS - 5 N2 - BACKGROUND: Peripheral neuropathy (PN) is one of the main toxicities associated with stavudine. Genetic variants in mitochondrial DNA (mtDNA) haplogroups have been associated with increased risk of developing PN in European non-Hispanic and black patients on stavudine containing antiretroviral therapy (ART). We investigated mtDNA haplogroups and their role in susceptibility to stavudine-induced peripheral in Malawian patients on ART. METHOD: Two hundred and fifteen adults on stavudine containing regimens were recruited from the ART clinic at Queen Elizabeth Central Hospital, Blantyre, into a cross-sectional study to investigate the effects of genetic variants in mtDNA of individuals in relation to response to treatment. Patients were categorized according to whether or not they had developed PN after a minimum of 6 months on stavudine containing ART. Whole mtDNA coding regions of each patient were sequenced, and CD4 count, viral load, and creatinine were determined. The mtDNA variation was correlated with clinical characteristics. RESULTS: Fifty-three (25%) of the participants developed PN after starting stavudine containing ART. Mitochondrial DNA subhaplogroup L0a2 was independently associated with increased risk of PN in a multivariate model (odds ratio, 2.23; 95% confidence interval, 1.14 to 4.39; P = 0.019), and subhaplogroup L2a was independently associated with reduced risk of PN (odds ratio, 0.39; 95% confidence interval, 0.16 to 0.94; P = 0.036). CONCLUSIONS: Genetic variation in mtDNA confers differential risk of developing PN in patients on stavudine containing ART among Malawians. SN - 1944-7884 UR - https://www.unboundmedicine.com/medline/citation/23614993/Mitochondrial_DNA_subhaplogroups_L0a2_and_L2a_modify_susceptibility_to_peripheral_neuropathy_in_malawian_adults_on_stavudine_containing_highly_active_antiretroviral_therapy_ L2 - https://doi.org/10.1097/QAI.0b013e3182968ea5 DB - PRIME DP - Unbound Medicine ER -