Source: Annual Congress 2002 - High altitude and hypoxia
Disease area: Pulmonary vascular diseases

Abstract

Previously we have demonstrated that high-altitude pulmonary hypertension (HAPH) in highlanders is associated with beta2-adrenergic receptors (BAR2) downregulation. The Gln27 genotype of BAR2 has decreased response to beta-agonists.The aim of our study was to investigate the association of Gln27Glu polymorphism of BAR2 gene with downregulation of BAR2 in HAPH patients. We studied 140 Kyrgyz male highlanders (54 healthy and 86 subjects with HAPH). The Gln27Glu and Arg16Gly polymorphisms of BAR2 gene were assayed by restriction of PCR products. BAR2 activity was evaluated in blood lymphocytes by assay of basal and isoproterenol-stimulated adenylate cyclase activities. The pulmonary haemodynamic was measured by right heart catheterization. The subject was diagnosed with HAPH when had a resting mean pulmonary arterial blood pressure (mPAP) higher than 22 mm Hg. Subjects with HAPH had downregulated BAR2-dependant activation of adenylate cyclase compared to normal highlanders. The isoproterenol stimulated adenylate cyclase activation was decreased in HAPH group compared to healthy highlanders (ΔcAMP 1.4±]0.3 vs 5.8±]2.3 fmol/10⁶ cells, respectively). The BAR2 gene polymorphism (Gln27Glu) study has demonstrated the disequilibrium of these alleles in two investigated groups. Patients with HAPH had a higher frequency of Gln/Gln homozygotic genotype compared to normals (62.4% vs 41.5%, p=0.039). The Arg16 and Gly16 alleles frequencies difference was not significant. We suggest that the downregulation of BAR2 in highlanders with HAPH is genetically determined by higher frequency of Gln27 genotype.

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A. A. Aldashev, B. B. Kalmyrzaev, T. Y. Mirzapoyazova, E. V. Kim, L. B. Mamanova, A. S. Sarybaev, A. S. Sydykov, B. K. Kojonazarov, M. R. Wilkins, N. W. Morrell (Bishkek, Kyrgyzstan; London, United Kingdom). The β-2 adrenoreceptor GLN27GLU gene polymorphism and high-altitude pulmonary hypertension in KYRGYZ highlanders. Eur Respir J 2002; 20: Suppl. 38, 691

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