High altitude pulmonary hypertension in Kyrgyz: association with the ACE genotype

摘要

Angiotensin-converting enzyme (ACE) has recently been implicated in the development of high altitude pulmonary hypertension (HAPH). The ACE I/D gene polymorphism is known to determine the level of plasma and tissue ACE. AIM: The aim of our study was to investigate whether there is an association between ACE I/D gene polymorphism and the development of HAPH in Kyrgyz highlanders. Methods: We determined the ACE genotype and its enzymatic activity in serum from 172 Kyrgyz highlanders (68 healthy subjects and 104 subjects with HAPH). Pulmonary artery haemodynamics were measured by right heart catheterization. Patients were diagnosed with HAPH when they: 1) lived at high altitude, 2) had a mean pulmonary arterial pressure (MPAP) higher than 25 mm Hg, 3) a pulmonary vascular resistance (PVR) greater than 200 Dyn/sec/m2 or 4) more than a 2-fold increase in MPAP or PVR when breathing 10% O2 for 30 min., 5) absence of other causes of increased pulmonary arterial pressure. Genomic DNA was extracted from blood samples and the ACE I/D genotype was determined by PCR. Results: Subjects with HAPH had a 2-fold higher frequency of the I/I homozygotic genotype than healthy subjects (44% vs. 13%, p<0.05). The frequency of the I allele in subjects with HAPH was about 1.5-fold greater than in healthy subjects (0.67 vs. 0.38, respectively, p<0.005). This allele was also associated with lower expression of ACE in plasma. Conclusions: We suggest that the II genotype is associated with the development of HAPH. The I allele of the ACE genotype could be a useful genetic marker of susceptibility to HAPH in high altitude populations.