title: Mitochondrial genomics and antiretroviral therapy-associated metabolic complications in HIV-infected Black South Africans: a pilot study.
abstract: 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.
authors: University of Cape Town Medical School, Department of Medicine, University of Cape Town, Cape Town, South Africa. phumla.sinxadi@uct.ac.za
authors: Phumla Z
authors: PZ
authors: Sinxadi
authors: Joel A
authors: JA
authors: Dave
authors: David C
authors: DC
authors: Samuels
authors: Jeannine M
authors: JM
authors: Heckmann
authors: Gary
authors: G
authors: Maartens
authors: Naomi S
authors: NS
authors: Levitt
authors: C William
authors: CW
authors: Wester
authors: David W
authors: DW
authors: Haas
authors: Todd
authors: T
authors: Hulgan
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects*; D044383:Black People / Q000235:genetics; D003430:Cross-Sectional Studies; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D054629:Genome, Mitochondrial; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000235:genetics*; D039682:HIV-Associated Lipodystrophy Syndrome / Q000209:etiology / Q000235:genetics; D006801:Humans; D015228:Hypertriglyceridemia / Q000209:etiology / Q000235:genetics; D008297:Male; D008659:Metabolic Diseases / Q000209:etiology* / Q000235:genetics*; D010865:Pilot Projects; D011115:Polyneuropathies / Q000209:etiology / Q000235:genetics; D013019:South Africa
chemical_list: D019380:Anti-HIV Agents; D004272:DNA, Mitochondrial