دورية أكاديمية
Mitochondrial genomics and antiretroviral therapy-associated metabolic complications in HIV-infected Black South Africans: a pilot study.
| العنوان: | Mitochondrial genomics and antiretroviral therapy-associated metabolic complications in HIV-infected Black South Africans: a pilot study. |
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| المؤلفون: | Sinxadi PZ; University of Cape Town Medical School, Department of Medicine, University of Cape Town, Cape Town, South Africa. phumla.sinxadi@uct.ac.za, Dave JA, Samuels DC, Heckmann JM, Maartens G, Levitt NS, Wester CW, Haas DW, Hulgan T |
| المصدر: | AIDS research and human retroviruses [AIDS Res Hum Retroviruses] 2013 Jul; Vol. 29 (7), pp. 1031-9. Date of Electronic Publication: 2013 Mar 15. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Mary Ann Liebert Country of Publication: United States NLM ID: 8709376 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1931-8405 (Electronic) Linking ISSN: 08892229 NLM ISO Abbreviation: AIDS Res Hum Retroviruses Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Larchmont, NY : Mary Ann Liebert Original Publication: [New York] : Mary Ann Liebert, [c1987- |
| مواضيع طبية MeSH: | Anti-HIV Agents/*adverse effects , DNA, Mitochondrial/*genetics , HIV Infections/*drug therapy , HIV Infections/*genetics , Metabolic Diseases/*etiology , Metabolic Diseases/*genetics, Adult ; Black People/genetics ; Cross-Sectional Studies ; Female ; Genetic Predisposition to Disease ; Genetic Variation ; Genome, Mitochondrial ; HIV Infections/complications ; HIV-Associated Lipodystrophy Syndrome/etiology ; HIV-Associated Lipodystrophy Syndrome/genetics ; Humans ; Hypertriglyceridemia/etiology ; Hypertriglyceridemia/genetics ; Male ; Pilot Projects ; Polyneuropathies/etiology ; Polyneuropathies/genetics ; South Africa |
| مستخلص: | Studies suggest that mitochondrial DNA (mtDNA) haplogroups are associated with antiretroviral therapy (ART)-related metabolic complications and distal sensory polyneuropathy (DSP), but there have been few studies in persons of African descent. We explored such associations in South African adults. Clinical and laboratory data and DNA specimens from a cross-sectional study were used. Sequencing and Phylotree determined African mtDNA subhaplogroups. Wilcoxon and regression analyses determined associations between mtDNA subhaplogroups and ART-related complications. The 171 participants represented six major haplogroups: L0 (n=78), L1 (n=3), L2 (n=30), L3 (n=53), L4 (n=1), and L5 (n=6). Analyses were restricted to 161 participants representing L0, L2, and L3: 78% were female; the median age was 36 years. All had been exposed to thymidine analogues, 42% were on lopinavir/ritonavir (lopinavir/r), and 58% were on either efavirenz or nevirapine. Median (IQR) ART duration was 22 (14-36) months. Median fasting triglycerides were 1.60 (1.13-1.75) and 1.04 (0.83-1.45) mmol/liter among L3e1 (n=22) and other subhaplogroups, respectively (p=0.003). Subhaplogroup L3e1 [adjusted OR (aOR) 3.16 (95% CI: 1.11-8.96); p=0.03] and exposure to lopinavir/r [aOR 2.98 (95% CI: 1.02-8.96); p=0.05] were independently associated with hypertriglyceridemia, after adjusting for age, sex, and ART duration. There were no significant associations between mtDNA haplogroups and cholesterol, dysglycemia, hyperlactatemia, or lipoatrophy, or DSP. Subhaplogroup L3e1 and lopinavir/r exposure were independently associated with hypertriglyceridemia in black South Africans on ART. This is the first report to link an African mtDNA variant with hypertriglyceridemia. If replicated, these findings may provide new insights into host factors affecting metabolic complications. |
| References: | Ann Hum Genet. 2005 Nov;69(Pt 6):639-44. (PMID: 16266403) AIDS. 2011 Jan 2;25(1):37-47. (PMID: 20871389) J Acquir Immune Defic Syndr. 2011 Dec 1;58(4):363-70. (PMID: 21792066) AIDS. 2005 Sep 2;19(13):1341-9. (PMID: 16103764) J Acquir Immune Defic Syndr. 2009 Jun 1;51(2):111-6. (PMID: 19339895) Nature. 2001 Dec 13;414(6865):807-12. (PMID: 11742413) Eur J Hum Genet. 2012 Jun;20(6):650-6. (PMID: 22258525) Antivir Ther. 2007;12(6):919-29. (PMID: 17926646) BMC Med Genet. 2009 Jun 18;10:60. (PMID: 19534826) J Acquir Immune Defic Syndr. 2008 Aug 1;48(4):381-8. (PMID: 18614930) Pharmacogenomics J. 2008 Feb;8(1):71-7. (PMID: 17684475) Environ Mol Mutagen. 2007 Apr-May;48(3-4):166-72. (PMID: 16758472) Diabetes Care. 2008 Jan;31 Suppl 1:S55-60. (PMID: 18165338) Gene. 1999 Sep 30;238(1):211-30. (PMID: 10570998) Muscle Nerve. 2010 May;41(5):599-606. (PMID: 20229576) J Acquir Immune Defic Syndr. 2011 Aug 1;57(4):284-9. (PMID: 21602696) Curr Opin Clin Nutr Metab Care. 2011 May;14(3):255-60. (PMID: 21460720) Mol Biol Evol. 2007 Mar;24(3):757-68. (PMID: 17194802) J Acquir Immune Defic Syndr. 2012 Feb 1;59(2):113-20. (PMID: 22245716) AIDS. 2008 Nov 30;22(18):2429-39. (PMID: 19005266) Hum Mutat. 2009 Feb;30(2):E386-94. (PMID: 18853457) J Acquir Immune Defic Syndr. 2011 Dec 1;58(4):371-8. (PMID: 21792063) Hum Mol Genet. 2002 Jun 15;11(13):1581-3. (PMID: 12045211) JAMA. 2001 May 16;285(19):2486-97. (PMID: 11368702) Hum Genet. 2001 Nov;109(5):521-5. (PMID: 11735027) Diabetologia. 2008 Apr;51(4):602-8. (PMID: 18251004) J Infect Dis. 2010 Jun 1;201(11):1703-7. (PMID: 20402593) J Infect Dis. 2008 Mar 15;197(6):858-66. (PMID: 18419350) J Antimicrob Chemother. 2005 May;55(5):800-4. (PMID: 15761071) Am J Hum Genet. 2006 Jul;79(1):54-61. (PMID: 16773565) Am J Hum Genet. 1997 Jun;60(6):1552-5. (PMID: 9199581) Mitochondrion. 2008 Jun;8(3):247-53. (PMID: 18538642) Antivir Ther. 2004 Apr;9(2):205-12. (PMID: 15134182) HIV Med. 2003 Jan;4(1):18-23. (PMID: 12534955) Antivir Ther. 2012;17(2):275-82. (PMID: 22293466) |
| معلومات مُعتمدة: | AI-054999 United States AI NIAID NIH HHS; P30AI 060354 United States AI NIAID NIH HHS; P30 AI060354 United States AI NIAID NIH HHS; UL1 TR000445 United States TR NCATS NIH HHS; AI-077505 United States AI NIAID NIH HHS; K23AI073141 United States AI NIAID NIH HHS |
| المشرفين على المادة: | 0 (Anti-HIV Agents) 0 (DNA, Mitochondrial) |
| تواريخ الأحداث: | Date Created: 20130223 Date Completed: 20130910 Latest Revision: 20221207 |
| رمز التحديث: | 20221213 |
| مُعرف محوري في PubMed: | PMC3685683 |
| DOI: | 10.1089/AID.2012.0373 |
| PMID: | 23428049 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1931-8405 |
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| DOI: | 10.1089/AID.2012.0373 |