Characterization of high-altitude pulmonary hypertension in the Kyrgyz: association with angiotensin-converting enzyme genotype.
Previous studies have suggested a genetic component in susceptibility to hypoxia-induced pulmonary hypertension. We therefore estimated the prevalence of high-altitude pulmonary hypertension (HAPH) in a Kyrgyz population and whether the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene associates with HAPH. An electrocardiographic survey of 741 highlanders demonstrated electrocardiogram signs of cor pulmonale in 14% of subjects. Pulmonary artery hemodynamics measured in an independent group of 136 male highlanders with symptoms of dyspnea at altitude revealed established pulmonary hypertension (mean pulmonary artery pressure [MPAP] > or = 25 mm Hg) in 20%. However, 26% of the normal subjects demonstrated an exaggerated response (twofold or greater increase in MPAP) to inhalation of 11% oxygen, and were classified as hyperresponsive. Ten-year follow-up of this group revealed increases in the MPAP, but not in normal subjects. Comparison of ACE I/D genotypes in the catheterized group revealed a threefold higher frequency of the I/I genotype in highlanders with HAPH, compared with normal highlanders (chi2 = 11.59, p = 0.003). In addition, MPAP was higher in highlanders with the I/I genotype (26.9 +/- 4.0 mm Hg) compared with the I/D genotype (20.6 +/- 1.2 mm Hg) or the D/D genotype (18.3 +/- 0.9 mm Hg) (p < 0.05). We conclude that HAPH is associated with ACE I/D genotype among Kyrgyz highlanders and the development of HAPH in this population and may be predicted by hyperresponsiveness to acute hypoxia.
Aldashev
Almaz A
AA
National Center for Cardiology and Internal Medicine, Bishkek, Kyrgyzstan. nwm23@cam.ac.uk
Sarybaev
Akpay S
AS
Sydykov
Akyl S
AS
Kalmyrzaev
Bolot B
BB
Kim
Elena V
EV
Mamanova
Lira B
LB
Maripov
Rashid
R
Kojonazarov
Baktybek K
BK
Mirrakhimov
Mirsaid M
MM
Wilkins
Martin R
MR
Morrell
Nicholas W
NW
D000293:Adolescent; D000328:Adult; D000368:Aged; D000403:Airway Resistance / Q000502:physiology; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism; D006328:Cardiac Catheterization; D004562:Electrocardiography; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D005787:Gene Frequency / Q000235:genetics; D005819:Genetic Markers / Q000502:physiology; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006352:Heart Ventricles / Q000473:pathology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D007707:Kyrgyzstan / Q000453:epidemiology; D008168:Lung / Q000098:blood supply / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism; D011110:Polymorphism, Genetic / Q000235:genetics; D015995:Prevalence; D011660:Pulmonary Heart Disease / Q000097:blood / Q000453:epidemiology / Q000235:genetics; D011669:Pulmonary Wedge Pressure / Q000502:physiology; D014797:Vital Capacity / Q000502:physiology
D001425:Bacterial Outer Membrane Proteins; D005819:Genetic Markers; D008562:Membrane Glycoproteins; C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A