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(Circulation. 1998;97:1124-1128.)
© 1998 American Heart Association, Inc.

Clinical Investigation and Reports

Association of High-Altitude Pulmonary Edema With the Major Histocompatibility Complex

Masayuki Hanaoka, MD; Keishi Kubo, MD; Yoshitaka Yamazaki, MD; Takashige Miyahara, MD; Yukinori Matsuzawa, MD; Toshio Kobayashi, MD; Morie Sekiguchi, MD; Masao Ota, PhD; ; Hideto Watanabe, MD

From the First Department of Medicine (M.H., K.K., Y.Y., T.M., Y.M., T.K., M.S.) and Department of Legal Medicine (M.O.), Shinshu University School of Medicine, Matsumoto, Japan, and Toyama Citizen Hospital (H.W.), Toyama, Japan.

Correspondence to Keishi Kubo, MD, First Department of Medicine, Shinshu University School of Medicine, 3–1-1 Asahi, Matsumoto, 390 Japan.

Background—A constitutional susceptibility has been suggested in the development of high-altitude pulmonary edema (HAPE) because HAPE generally affects healthy young people, some of whom suffer recurrent episodes. We examined whether immunogenetic susceptibility is present in HAPE-susceptible subjects.

Methods and Results—The frequencies of human leukocyte antigen (HLA) alleles in 28 male and 2 female subjects with a history of HAPE were compared with those in 100 healthy volunteers. We assayed the HLA-A, -B, -C, -DR, and -DQ antigens serologically. The pulmonary hemodynamics on admission to the hospital and the ventilatory response to hypoxia and hypercapnia were retrospectively examined in 10 of the HAPE-susceptible subjects. HLA-DR6 was positive in 14 (46.7%) of the subjects with HAPE but only 16.0% of the control subjects (P=.0005), and HLA-DQ4 was positive in 12 (40.0%) of the subjects with HAPE but only 10.0% of the control subjects (P=.0001). HLA-DR6 or HLA-DQ4 was positive in 8 (100%) of the subjects with recurrent HAPE. The pulmonary arterial pressure on admission of the HLA-DR6–positive subjects with HAPE was significantly higher than that of the HLA-DR6–negative subjects with HAPE.

Conclusions—There were significant associations of HAPE with HLA-DR6 and HLA-DQ4 and of pulmonary hypertension with HLA-DR6. An immunogenetic susceptibility, which is associated with HLA class II alleles located within the major histocompatibility complex, may underlie the development of HAPE, at least in some of its forms.

Key Words: edema • genetics • hemodynamics • hypertension, pulmonary • ventilation

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