title: Mitochondrial Haplogroups and Risk of Pulmonary Arterial Hypertension.
abstract: Pulmonary arterial hypertension (PAH) is a serious and often fatal disease. It is a panvasculopathy of the pulmonary microcirculation characterized by vasoconstriction and arterial obstruction due to vascular proliferation and remodeling and ultimately right ventricular failure. Mitochondrial dysfunction is a universal finding in pulmonary vascular cells of patients with PAH, and is mechanistically linked to disease origins in animal models of pulmonary hypertension. Mitochondria have their own circular DNA (mtDNA), which can be subgrouped into polymorphic haplogroup variants, some of which have been identified as at-risk or protective from cardiovascular and/or neurodegenerative diseases. Here, we hypothesized that mitochondrial haplogroups may be associated with PAH. To test this, mitochondrial haplogroups were determined in a cohort of PAH patients and controls [N = 204 Caucasians (125 PAH and 79 controls) and N = 46 African Americans (13 PAH and 33 controls)]. Haplogroup L was associated with a lower rate of PAH as compared to macrohaplogroups N and M. When haplogroups were nested based on ancestral inheritance and controlled for age, gender and race, haplogroups M and HV, JT and UK of the N macro-haplogroup had significantly higher rates of PAH compared to the ancestral L (L0/1/2 and L3) (all p ≤ 0.05). Overall, the findings suggest that mitochondrial haplogroups influence risk of PAH and that a vulnerability to PAH may have emerged under the selective enrichment of specific haplogroups that occurred with the migration of populations out of Africa.
authors.affiliation: Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio, United States of America.
authors.forename: Samar
authors.initials: S
authors.lastname: Farha
authors.affiliation: Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio, United States of America.
authors.forename: Bo
authors.initials: B
authors.lastname: Hu
authors.affiliation: Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio, United States of America.
authors.forename: Suzy
authors.initials: S
authors.lastname: Comhair
authors.affiliation: Respiratory Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio, United States of America.
authors.forename: Joe
authors.initials: J
authors.lastname: Zein
authors.affiliation: Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio, United States of America.|Respiratory Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio, United States of America.
authors.forename: Raed
authors.initials: R
authors.lastname: Dweik
authors.affiliation: Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio, United States of America.|Respiratory Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio, United States of America.
authors.forename: Serpil C
authors.initials: SC
authors.lastname: Erzurum
authors.affiliation: Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio, United States of America.|Genomic Medicine Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio, United States of America.
authors.forename: Micheala A
authors.initials: MA
authors.lastname: Aldred
mesh_terms: D001741:Black or African American; D015331:Cohort Studies; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D006239:Haplotypes; D006801:Humans; D006976:Hypertension, Pulmonary / Q000208:ethnology / Q000235:genetics*; D008297:Male; D044465:White People
chemical_list: D004272:DNA, Mitochondrial