Polymorphisms of the tyrosine hydroxylase gene in subjects susceptible to high-altitude pulmonary edema

Study objectives A blunted hypoxic ventilatory response (HVR) has been observed in some sufferers of high-altitude pulmonary edema (HAPE), and was proposed as a potential mechanism in its pathogenesis. Tyrosine hydroxylase (TH) is a rate-limiting enzyme in the carotid body responding to hypoxia to synthesize dopamine neurotransmitter to heighten ventilation. The association of constitutional susceptibility to HAPE regarding the blunted HVR aspect with polymorphisms of the TH gene was examined. Design A cross-sectional case control study. Setting Shinshu University Hospital, Matsumoto, Japan. Participants Forty-three subjects with a history of HAPE (HAPE group) and 51 healthy climbers without a history of HAPE (control group). Measurements The (TCAT)n tetranucleotide microsatellite repeats within intron 1 and Met81Val variant in exon 2 of the TH gene were investigated by polymerase chain reaction following either direct sequencing or restriction fragment length polymorphism. The HVR in 21 subjects among the HAPE group was also measured. Results No significant frequency differences could be found in terms of either of the two polymorphisms between the HAPE and control groups. Meanwhile, no relationships were observed between the HVR values of HAPE subjects and the individual alleles in both polymorphisms of the TH gene. Conclusion The genetic susceptibility of HAPE, specifically the blunted HVR in HAPE, is probably not associated with the mutations of the TH gene, implying that these two polymorphisms may not be a sufficient genetic marker for predicting a predisposition to the susceptibility to HAPE.