Understanding etiopathology of high altitude induced venous thrombo-embolism (HA-VTE) by variant analysis using whole exome sequencing (WES) data

Abstract

BackgroundVenous thrombo-embolsim(VTE) is a complex disease and a significant cause of morbidity and mortality worldwide. Its manifestation attributes to various acquired and genetic risk factors. Environmental condition at high altitude (HA) such as hypoxia (oxygen deprivation) has been regarded as independent risk factor for VTE. Individual variations in coagulation genes play a major role in predisposing a person towards VTE. MethodologyPresent study evaluates genetic variants in VTE patients from HA (n = 6) and from sea level(SL) (n = 15) in comparison to healthy controls (n = 19). To unfold a unique thrombophilia panel in Indian population, whole exome sequencing (WES) was performed on IlluminaHiSeq platform. Presence or absence of known variants was studied across the three study groups. Statistically significantly variants were enlisted for each study group. ResultsOur findings suggest that VTE pathology is associated with total 38 variants in pro-coagulant and anti-coagulant genes. These variants were distinct for HA-VTE and SL-VTE patients. Eighteen significant variants in HA-VTE group primarily included coagulation factors, rs6035 and rs6030 in F5 gene; rs3136434, rs216311, rs216902 and rs2192205 in F2 gene and anti-coagulants, rs2759328 in SERPINC1 and rs758232970 in PROS1 gene. Amongst 7 significant variants in SL-VTE, rs6035 was common with HA-VTE. Besides, 13 variants significantly appeared when the two patient groups, HA-VTE and SL-VTE were compared with each other. ConclusionWES study delineated variants in VTE patients, from HA and SL. Our findings have generated a unique thrombophilia panel which could be helpful in predicting individual's susceptibility towards VTE at HA and even at SL.