Angiotensin Converting Enzyme Genotypes in Relation to High Altitude Hypoxia Among the Tawang Monpa from Himalayan Mountains
Angiotensin converting enzyme (ACE) plays an important role in cardiovascular homeostasis. A polymorphism in the human ACE gene has been identified in which the presence (insertion, I allele) rather than the absence (deletion, D allele) is associated with tissue ACE activity (Woods and Montgomery 2001). Previous studies suggest that ACE gene insertion/deletion (I/D) polymorphism has significant genetic influence on high altitude natives. In particular, it has observed that the I-allele is associated with higher arterial oxygen saturation, where an excess of I- allele has been reported in high altitude natives from Peru (Bigham et al. 2008) and Ladakh (Qadar Pasha et al. 2001). With this in mind, the present exploratory study tries to scrutinize whether excess of I- allele in high altitude natives is a universal phenomenon. The study aims to examine the ACE genotypes distribution among the Tawang Monpa with special emphasis on its association with arterial oxygen saturation and other physiological parameters. A total number of 200 adult Monpa (between the ages of 18-35) were recruited in Tawang Town at ~3,200 m above sea level. For each participant, we collected 4 ml intravenous blood for DNA isolation and genotyping of ACE polymorphisms. We also measured height and weight and calculated the body mass index (BMI, kg/m2). Percent body fat (%BF) was estimated from bicep, tricep, subscapular, and suprailiac skin-fold measurements using the prediction equations of Durnin and Womersley (1974). Transcutaneous arterial oxygen saturation (SaO2) was measured at rest using a fingertip pulse oximeter. Hemoglobin concentration was measured from a fingertip blood drop using a Hemocue portable hemoglobin analyzer. Forced vital capacity (FVC) and forced expiratory volume in 1-second (FEV1) were measured on each participant following standard protocols
Interestingly, unlike other high altitude natives who exhibit high frequencies of II homozygotes, Tawang Monpa shows significantly high frequency of ID heterozygotes (p< 0.0001). Consequently, both I (0.48) and D (0.52) alleles show equivalent frequencies in this population. Arterial oxygen saturation at rest does not show any association with ACE I/D polymorphism in this population, which is consistent with previous study (Woods et al. 2002). However, mean arterial blood pressure is considerably high in DD homozygotes as compared to either II homozygotes or ID heterozygotes. In conclusion, it is possible that perhaps the D -allele has certain genetic significance for adaptation to high altitude hypoxia in Tawang Monpa. Moreover, previous study has suggested disadvantage of I- allele among highlanders with respect to high altitude pulmonary edema (HAPE) and consequent high frequency of HAPE in II homozygotes (Aldashev et al. 2002). Nevertheless, before concluding anything substantially and to understand how D -allele is benefiting this population, more research is required in this direction among Tawang Monpa.