Angiotensin-Converting Enzyme (ACE) gene polymorphism and arterial blood pressure among the Tawang Monpa of Eastern Himalayan Mountains: Is there a signature of natural selection?

OBJECTIVES: The present paper aims to characterize the Angiotensin-converting enzyme (ACE) genotype, with particular emphasis on its association with arterial oxygen saturation, arterial blood pressure, hemoglobin [Hb] concentration, and ventilatory measures among the Tawang Monpa, a high-altitude native population of the Eastern Himalaya, India. METHODS: A cross-sectional sample of 168Monpa participants from Tawang town, Arunachal Pradesh, India, was selected who live at an altitude of ∼3,200 meters (m) above sea level. For each participant, height, weight, and skinfold thickness were measured, based on which body mass index (BMI, kg/m(2)) and percentage of body fat (%BF) were calculated. Physiological measures, such as the transcutaneous arterial oxygen saturation (SaO(2)), hemoglobin [Hb] concentration, forced vital capacity (FVC), forced expiratory volume in 1-second (FEV(1)), and systemic arterial blood pressure were measured. First, the peripheral venous blood samples (four ml) were drawn, and then white blood cells were separated for the ACE genotyping of each participant. RESULTS: Unlike high-altitude natives from Peru and Ladakh, who exhibit high frequencies of II homozygotes, the Tawang Monpa shows a significantly high frequency of ID heterozygotes (p<0.0001). In addition, no significant association was identified between ACE gene polymorphism and arterial blood pressure, oxygen saturation at rest, vital capacity, or [Hb] concentration. DISCUSSION: The results suggest that the association of the ACE gene with resting SaO(2) is inconsistent across native populations living under hypobaric hypoxia. Further, ACE I/D gene polymorphism may not be under natural selection in specific native populations, including Tawang Monpa, for their adaptation to high-altitude hypoxia.