Human exome analysis of candidate genetic variants for susceptibility to high-altitude pulmonary edema in Japanese

Abstract

High-altitude pulmonary edema (HAPE) is a non-cardiogenic pulmonary edema that develops in unacclimatized healthy individuals at altitudes above 2,500 m. Previous studies suggest genetic component in its etiology of HAPE, however, the genetic basis remains mostly unknown. We performed the whole-exome sequencing (WES) on 4 HAPE susceptible (HAPE-s) and 4 HAPE resistant (HAPE-r) subjects of Japanese in order to capture the genetic variants related with the susceptibility to HAPE. The DNA samples from 4 HAPE-s and 4 HAPE-r subjects were performed with WES by Rikengenesis Co., Ltd in Japan. The whole exome was captured with the SureSelect Human All Exon V6 Kit (Agilent) by using HiSeq 2500 instrument (Illumina) according to the protocol. All data was filtered out the data in low quality, false positive and false negative according to the default criteria. As a result, 29,671 variants were used for analysis in the present study. Due to the limited number of sample, we directly counted the number of alleles other than any statistical methods. With a self-determined rule in which the homozygous major alleles in all HAPE-r versus the heterozygous and homozygous minor alleles in HAPE-s, we detected 24 variants on exomes in 24 genes. In addition, we hunted the known candidate variants that were reported previously and found that the minor alleles of these variants were indeed shown more numbers in HAPE-s than HAPE-r subjects. Several candidate genetic variants and genes were dominantly detected in Japanese HAPE-s comparing with HAPE-r subjects by WES. The results suggests that genetic component is undoubtedly involved with the susceptibility to HAPE in Japanese