European Mitochondrial DNA Haplogroups and Metabolic Disorders in HIV/HCV-Coinfected Patients on Highly Active Antiretroviral Therapy

Abstract

Mitochondrial DNA (mtDNA) haplogroups play an important role in susceptibility to metabolic disorders and cardiovascular disease. We carried out a cross-sectional study in 248 HIV/hepatitis C virus-coinfected patients on highly active antiretroviral therapy to investigate whether mtDNA haplogroups had any influence on metabolic disorders. mtDNA genotyping was performed using the Sequenom MassARRAY platform. Insulin resistance (IR) was estimated using the homeostatic model assessment (HOMA) (HOMA ≥ 3.8), which was calculated as fasting plasma glucose (mmol/L) times fasting serum insulin (mU/L) divided by 22.5. A high atherogenic risk was assessed when the atherogenic index (AI) was ≥3.5. AI was calculated as total cholesterol (mg/dL) divided by HDL (mg/dL). The major haplogroup HV and haplogroup H had reduced odds ratios of IR (HOMA ≥ 3.8) [0.45 (95% CI: 0.24 to 0.85) and 0.36 (95% CI: 0.18 to 0.69), respectively], and high AI (AI ≥ 3.5) [0.44 (95% CI: 0.22 to 0.87) and 0.40 (95% CI: 0.19 to 0.80), respectively]. The major haplogroup U had increased odds of IR [2.66 (95% CI: 1.39 to 5.8)]. The major haplogroup JT and haplogroup T had increased odds of high AI [2.86 (95% CI: 1.29 to 6.33) and 4.01 (95%CI: 1.59 to 10.03), respectively]. Additionally, we found that patients belonging to the major haplogroup HV had lower values of serum hepatic growth factor and nerve growth factor, and higher values of adiponectin than patients belonging to the major haplogroup JT (P < 0.05). mtDNA haplogroups were associated with IR and atherogenic dyslipidemia; suggesting that mitochondrial genomics may play a significant role in metabolic disorders and cardiovascular diseases in HIV/hepatitis C virus-coinfected patients on highly active antiretroviral therapy.