Background
Mitochondrial dysfunction is implicated in the development of heart failure, which is more common in people with HIV (PWH) than those without HIV (PWoH). Whether genetic variations in mitochondrial DNA (mtDNA) are related to cardiac dysfunction, specifically left ventricular diastolic dysfunction (LVDD), has not been well studied in PWH.
Methods
We included men from the Multicenter AIDS Cohort Study (MACS) and women from the Women’s Interagency HIV Study (WIHS) who participated in standardized echocardiographic studies. LVDD was defined using the Characterizing Heart Function on Antiretroviral Therapy (CHART) study criteria, which excludes individuals with reduced LV ejection fraction. mtDNA haplogroups were inferred from genotyping data using HaploGrep. We used multivariable logistic regression to examine the sex- and race-stratified association between LVDD and common African haplogroups (L0L1, L2, L3, or “other”) for males and females or European haplogroups (H, UK, JT, or “other”) for males. We further evaluated for interactions between HIV serostatus and haplogroups. The model controlled for principal components of nuclear genetic ancestry, age, BMI, educational level, alcohol intake, hepatitis C status, and clinical characteristics relevant for LVDD (hypertension, diabetes mellitus, dyslipidemia, and eGFR).
Results
Among 842 men (455 PWH and 387 PWoH), 574 self-identified as White and 268 as Black with a median age of 59 [IQR: 46, 72] and prevalence of LVDD of 24.2% (24.2% PWH and 24.3% PWoH). All 591 women (397 PWH and 194 PWoH) self-identified as Black with a median age of 52 [IQR: 40, 64] and prevalence of LVDD of 26.9% (27.0% PWH and 26.8% PWoH). For men with HIV, the odds of LVDD were 48% lower in European haplogroup H than for men in non-H haplogroups (OR, 0.52; 95% CI, 0.28-0.97; Figure). There were no significant associations between haplogroups of African origin and LVDD in men. For women with HIV, the odds of LVDD were 57% lower in African haplogroup L2 (OR, 0.43; 95% CI, 0.22-0.81; Figure). HIV status significantly modified the association of haplogroup L2 and LVDD in women (Pinteraction=0.025). For PWoH, there were no significant associations between haplogroups and LVDD.
Conclusions
Common mitochondrial haplogroups (i.e. H, L2) are significantly associated with lower odds of LVDD among PWH, but not among PWoH. Mitochondrial genetic variations may protect against cardiac diastolic dysfunction in the setting of HIV infection, particularly among Black women.