EGLN1
involvement in high-altitude adaptation revealed through genetic analysis of extreme constitution types defined in Ayurveda
Authors: Aggarwal Shilpi , Negi Sapna , Jha Pankaj , Singh Prashant K. , Stobdan Tsering , Pasha M. A. Qadar , Ghosh Saurabh , Agrawal Anurag ,   Indian Genome Variation Consortium, Prasher Bhavana , Mukerji Mitali ,   The Indian Genome Variation Consortium is composed of the following additional members:, Brahmachari S. K. , Majumder P. P. , Mukerji M. , Habib S. , Dash D. , Ray K. , Bahl S. , Singh L. , Sharma A. , Roychoudhury S. , Chandak G. R. , Thangaraj K. , Parmar D. , Sengupta S. , Bharadwaj D. , Rath S. K. , Singh J. , Jha G. N. , Virdi K. , Rao V. R. , Sinha S. , Singh A. , Mitra A. K. , Mishra S. K. , Pasha Q. , Sivasubbu S. , Pandey R. , Baral A. , Singh P. K. , Sharma A. , Kumar J. , Stobdan T. , Bhasin Y. , Chauhan C. , Hussain A. , Sundaramoorthy E. , Singh S. P. , Bandyopadhyay A. , Dasgupta K. , Reddy A. K. , Spurgeon C. J. , Idris M. M. , Khanna V. , Dhawan A. , Anand M. , Shankar R. , Bharti R. S. , Singh M. , Singh A. P. , Khan A. J. , Shah P. P. , Pant A. B. , Kaur R. , Bisht K. K. , Kumar A. , Rajamanickam V. , Wilson E. , Thangadurai A. , Jha P. K. , Maulik M. , Makhija N. , Rahim A. , Sharma S. , Chopra R. , Rana P. , Chidambaram M. , Maitra A. , Chawla R. , Soni S. , Khurana P. , Khan M. N. , Sutar S. D. , Tuteja A. , Narayansamy K. , Shukla R. , Prakash S. , Mahurkar S. , Mani K. Radha , Hemavathi J. , Bhaskar S. , Khanna P. , Ramalakshmi G. S. , Tripathi S. M. , Thakur N. , Ghosh B. , Kukreti R. , Madan T. , Verma R. , Sudheer G. , Mahajan A. , Chavali S. , Tabassum R. , Grover S. , Gupta M. , Batra J. , Kumar A. , Nejatizadeh A. , Vaid M. , Das S. K. , Sharma S. , Sharma M. , Chatterjee R. , Paul J. A. , Srivastava P. , Rajput C. , Mittal U. , Singh M. , Hariharan M. , Das S. , Chaudhuri K. , Sengupta M. , Acharya M. , Bhattacharyya A. , Saha A. , Biswas A. , Chaki M. , Gupta A. , Mukherjee S. , Mookherjee S. , Chattopadhyay I. , Banerjee T. , Chakravorty M. , Misra C. , Monadal G. , Sengupta S. , Dutta De. D. , Bajaj S. , Deb I. , Banerjee A. , Chowdhury R. , Banerjee D. , Kumar D. , Das S. R. , Tiwari S. , Bharadwaj A. , Khanna S. , Ahmed I. , Parveen S. , Singh N. , Dasgupta D. , Bisht S. S. , Rajput R. , Ghosh B. , Kumar N. , Chaurasia A. , Abraham J. K. , Sinha A. , Scaria V. , Sethi T. P. , Mandal A. K. , Mukhopadhyay A. 
Published: October 2010

It is being realized that identification of subgroups within normal controls corresponding to contrasting disease susceptibility is likely to lead to more effective predictive marker discovery. We have previously used the Ayurvedic concept of
Prakriti
, which relates to phenotypic differences in normal individuals, including response to external environment as well as susceptibility to diseases, to explore molecular differences between three contrasting
Prakriti
types:
Vata, Pitta, and Kapha
. EGLN1
was one among 251 differentially expressed genes between the
Prakriti
types. In the present study, we report a link between high-altitude adaptation and common variations rs479200 (C/T) and rs480902 (T/C) in the
EGLN1
gene. Furthermore, the TT genotype of rs479200, which was more frequent in
Kapha
types and correlated with higher expression of
EGLN1
, was associated with patients suffering from high-altitude pulmonary edema, whereas it was present at a significantly lower frequency in
Pitta
and nearly absent in natives of high altitude. Analysis of Human Genome Diversity Panel-Centre d’Etude du Polymorphisme Humain (HGDP-CEPH) and Indian Genome Variation Consortium panels showed that disparate genetic lineages at high altitudes share the same ancestral allele (T) of rs480902 that is overrepresented in
Pitta
and positively correlated with altitude globally (
P
< 0.001), including in India. Thus,
EGLN1
polymorphisms are associated with high-altitude adaptation, and a genotype rare in highlanders but overrepresented in a subgroup of normal lowlanders discernable by Ayurveda may confer increased risk for high-altitude pulmonary edema.