Polymorphisms in pulmonary surfactant protein A1 (SP-A1) and A2 (SP-A2) genes and susceptibility to high altitude pulmonary edema (HAPE)

Abstract

Rationale Mal-acclimatization at high altitude causes alterations in pulmonary surfactant activity, leading to development of high altitude pulmonary edema (HAPE). Surfactant protein A (SP-A), encoded by SP-A1 and SP-A2, has a regulatory role in the maintenance of pulmonary surfactant activity. The association of HAPE with polymorphisms of SP-A1 and SP-A2 and its correlation with biochemical parameters has been examined in Indian population. Methods 16 LAN controls (acclimatized at high altitude >3500 m), 15 LAN HAPE patients and 19 HAN controls were studied. SP-A1 and SP-A2 were amplified, sequenced and allele frequencies were compared among subjects. Some of biochemical parameters in blood related to oxidative stress, membrane permeability and vascular tone were estimated in subjects of the above three groups. Results Eight loci each in SP-A1 (C1101T; C1162T; C1193G; C1416T; G1544A; T3150C; T3204C and T3246C) and SP-A2 (C1382G; T1492C; G1649C; A1660G; C2474T; A2491C; T3018C and A3265C) were found polymorphic. Significant differences in allele frequencies of four loci in SP-A1 (C1101T; T3150C; T3204C and T3246C) and two in SP-A2 (C2474T and A3265C) were observed in LAN HAPE patients and LAN controls (p<0.01). In HAPE patients estimated biochemical parameters indicated an increase in oxidative stress and reduced antioxidants, altered cell membrane permeability and vasoconstriction. Conclusions The genetic susceptibility of HAPE is associated with polymorphisms in SP-A1 and SP-A2. The polymorphisms significantly associated with HAPE subjects may be useful as potential genetic markers for predicting susceptibility to HAPE. Oxidative injury, cell membrane permeability and vasoactive molecules play an important role in the development of HAPE.