Biochemical and Biophysical Research Communications
Endothelin-1 gene variants and levels associate with adaptation to hypobaric hypoxia in high-altitude natives☆
Section snippets
Materials and methods
Study population. The institutional review committee approved the investigation. The subjects were apprised of the study and a written informed consent was obtained from each. A total of 662 healthy, unrelated subjects of Indian ethnicity, comprising of 426 highlanders (HLs) and 236 lowlanders (LLs), were recruited for the study. Both the HLs and LLs were permanent residents of their respective lands since ancient times [4], [29]. The two groups belong to North India, who had initially migrated
Characteristics of the subjects
Table 1 shows the characteristics of the HLs and LLs. The DBP was comparable in the two groups, whereas, SBP, BMI, and plasma ET-1 levels were significantly lower in the HLs than those in LLs. Notably, the ET-1 levels were 50% lower in the HLs than those in LLs (1.7 ± 0.7 vs 3.5 ± 0.5 pg/ml; p < 0.0001).
(CT)n–(CA)n repeat distribution in the HLs and LLs
Nineteen alleles of the microsatellite with repeats ranging between 13 and 45 were observed in the two groups (Table 2). The distribution of the repeats did not differ significantly when compared
Discussion
At HA, ET-1 due to its exaggerated release is thought to play an important role in the pathogenesis of HAPE [20], [21], which is life threatening in the absence of proper therapeutic measures [10]. It thus becomes crucial to offset the negative consequences of hypoxia in order to adapt to HA. Our finding of lower plasma ET-1 levels in the HLs is indicative of a protective role under hypoxic stress. It is likely that stimulation of ET-1 expression in response to hypoxia is controlled to a
Acknowledgments
The Council of Scientific and Industrial Research supported this work financially. Ven. Thubten Choegyal, Chairman, Ladakh Heart Foundation, Leh, and Mr. Mohd Iqbal, SNM Hospital, Leh, cooperated in collection of blood samples. We acknowledge our Director Prof. S.K. Brhamachari for his support and encouragement.
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Abbreviations: HA, high-altitude; ET-1, endothelin-1; HLs, highlanders; LLs, lowlanders; HAPE, high-altitude pulmonary edema; HACE, high-altitude cerebral edema; ACE, angiotensin converting enzyme; NOS3, endothelial nitric oxide synthase; LD, linkage disequilibrium; BP, blood pressure; SBP, systolic blood pressure; DBP, diastolic blood pressure; BMI, body mass index; D′, Lewontin’s coefficient; r2, squared correlation coefficient; NO, nitric oxide; I, insertion; D, deletion.
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Present address: Ladakh Institute of Prevention, Leh, Ladakh, Jammu & Kashmir, India.