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Published ahead of print on August 28, 2002, doi:10.1164/rccm.200204-345OC

Am. J. Respir. Crit. Care Med., Volume 166, Number 10, November 2002, 1396-1402

A more recent version of this article appeared on November 15, 2002
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Submitted on April 18, 2002
Accepted on August 23, 2002

Characterization of high altitude pulmonary hypertension in the Kyrgyz: Association with ACE genotype

Almaz A Aldashev1, Akpay S Sarybaev1, Akyl S Sydykov1, Bolot B Kalmyrzaev1, Elena V Kim1, Lira B Mamanova1, Rashid Maripov1, Baktybek K Kojonazarov1, Mirsaid M Mirrakhimov1, Martin R Wilkins2, and Nicholas W Morrell3*

1 Laboratory of Molecular Biology, National Center for Cardiology and Internal Medicine, Bishkek, Kyrgyzstan, 2 Section on Clinical Pharmacology, Imperial College School of Medicine, London, United Kingdom, 3 Department of Medicine, University of Cambridge, Cambridge, United Kingdom

* To whom correspondence should be addressed. E-mail: nwm23{at}cam.ac.uk.

Previous studies have suggested a genetic component to the susceptibility to hypoxia-induced pulmonary hypertension. Thus we estimated the prevalence of high altitude pulmonary hypertension (HAPH) in a Kyrgyz population and whether the insertion/deletion (I/D) polymorphism of the ACE gene associates with HAPH. An electrocardiographic survey of 741 highlanders demonstrated ECG signs of cor pulmonale in 14% of subjects. Pulmonary artery hemodynamics measured in an independent group of 136 male highlanders with symptoms at altitude, revealed established pulmonary hypertension (MPAP>=25mmHg) in 20%. However, 26% of the normal subjects demonstrated an exaggerated response (>=2-fold increase in MPAP) to inhalation of 11% oxygen, and were classified as hyper-responsive. 10 year follow up of this group revealed increases in the MPAP, but not in normals. Comparison of ACE I/D genotypes in the catheterized group revealed a 3-fold higher frequency of the I/I genotype in highlanders with HAPH, compared with normal highlanders ({chi} 11.59, p=0.003). In addition, MPAP was higher in highlanders with the I/I (26.9±4.0mmHg) compared with the I/D (20.6±1.2mmHg, or the D/D genotype (18.3±0.9mmHg) (P<0.05). We conclude that HAPH is associated with ACE I/D genotype amongst Kyrgyz highlanders and the development of HAPH in this population may be predicted by hyper-responsiveness to acute hypoxia.
Key words: pulmonary hypertension, hypoxia, angiotensin converting enzyme,altitude




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