Common Inherited Mitochondrial Dna Mutations and Nucleoside Reverse Transcriptase Inhibitor-Induced Severe Hyperlactataemia in HIV-Infected Adults: An Exploratory Study
| Autor: | Neil Bradman, Martine Bolhaar, Catherine J. E. Ingram, Peter Reiss, Lilanganee Telisinghe, Alan Karstaedt, Alison D. Grant, Rosemary Ekong, Alejandro Arenas-Pinto, Rainer Weber, Ian V. D. Weller |
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| Přispěvatelé: | Amsterdam institute for Infection and Immunity, Amsterdam Public Health, Global Health, University of Zurich, Arenas-Pinto, Alejandro |
| Rok vydání: | 2012 |
| Předmět: |
Adult
Male Mitochondrial DNA Anti-HIV Agents Respiratory chain Black People 610 Medicine & health HIV Infections Biology medicine.disease_cause DNA Mitochondrial Polymorphism Single Nucleotide Haplogroup White People Nucleoside Reverse Transcriptase Inhibitor 10234 Clinic for Infectious Diseases chemistry.chemical_compound Polymorphism (computer science) Hiv infected medicine 2736 Pharmacology (medical) Humans Pharmacology (medical) Sequence Deletion Genetics Pharmacology Mutation 2725 Infectious Diseases Middle Aged medicine.disease Virology Mitochondria Didanosine Stavudine 3004 Pharmacology Infectious Diseases chemistry Lactic acidosis Case-Control Studies Leukocytes Mononuclear Reverse Transcriptase Inhibitors Acidosis Lactic Female Zidovudine DNA |
| Zdroj: | Antiviral therapy, 17(2), 275-282. International Medical Press Ltd |
| ISSN: | 2040-2058 1359-6535 |
| DOI: | 10.3851/imp2259 |
| Popis: | Background Genetic predisposition to dideoxynucleoside-induced mitochondrial dysfunction might be related to mitochondrial DNA (mtDNA) polymorphisms. Severe hyperlactataemia is probably the best model to assess such a predisposition. Methods For this exploratory study in White European and Black African HIV-infected adults, hypervariable region 1 of mtDNA samples from peripheral blood mono-nuclear cells or buccal smears of patients who have developed confirmed severe hyperlactataemia was sequenced. Additionally, 21 single nucleotide polymorphisms and a 9 bp deletion were genotyped to assign mtDNA haplogroups. Finally, entire mtDNA sequencing was performed in a subset of European samples. Samples were obtained from Black African cases and controls recruited from a single centre in Johannesburg, South Africa and from white European cases from Amsterdam, London and Zurich. Results A total of 40 cases and 38 controls from Johannesburg were included. All of the cases and 33 controls were receiving stavudine-based therapy at the time of the index date ( P=0.024). The distribution of mtDNA haplotypes was not different between cases and controls ( P=0.137), and neither were the predicted haplogroups ( P=0.751). In total, 11 of the 12 European cases were on stavudine and/or didanosine at the time of the event. No hypervariable region 1 haplotype was consistently found in the European cases. Sequencing of the entire mtDNA from three of these cases supported the absence of any shared mutations other than major alleles frequently seen in the mtDNA database. Conclusions We did not find an association between homoplasmic inherited mtDNA polymorphisms and severe hyperlactataemia. Our data do not support the existence of non-synonymous mtDNA mutations that explain an increased predisposition to dideoxynucleoside-induced mitochondrial dysfunction. |
| Databáze: | OpenAIRE |
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