Genetic Susceptibility Study Between NR3C1 Gene Polymorphisms And High Altitude Pulmonary Edema

Objective To investigate the association between NR3C1 gene polymorphisms and the susceptibility of high altitude pulmonary edema(HAPE).Methods The study enrolled 133 HAPE patients and 135 healthy controls during 2010 to 2017 in Qinghai.The exons of NR3C1 gene were sequenced by a ABI 3730 DNA analyzer.The candidate SNPs of NR3C1 gene were genotyped by Sequenom Mass ARRAY?SNP in all subjects.Hardy-Weinberg equilibrium(HWE)was used to assess the goodness of fit of the genotypes;Chi-square test was used to calculate the differences of genotype and allele distributions;Odds ratios(ORs)with corresponding 95% confidence intervals(95% CIs)were used to analyze the association between the NR3C1 gene and HAPE.Result 1.The sequencing results showed that the exons of NR3C1 gene had no change except exon 6 and exon9 between two groups.There are two heterozygous substitutions at codon 588(rs6194)in exon 6 and 766(rs6196)in exon 9,respectively.The genotypic distributions and allelic frequencies of NR3C1 SNP rs6194 showed significant differences in two groups(P < 0.05).The frequencies of the C allele were significantly higher in the HAPE group than in the control group(P < 0.05)with an odds ratio of 3.009(95% CI = 1.250-7.244).There were no differences in genotypic and allelic frequencies in rs6196 polymorphism between the two groups.2.The results of genotyping in candidate SNPs showed rs10052957,rs41423247 and rs6188 were significantly different between two groups.The genotypic frequencies of rs10052957,rs41423247,rs6188 significantly associated with HAPE with Odds Ratio [OR(95%): 1.939(1.062-3.542)(P=0.03)],[OR(95%): 1.795(1.018-3.615)(P=0.04)],[OR(95%): 1.959(1.072-3.579)(P=0.027)].The allelic frequencies of rs10052957,rs41423247,rs6188 were also significantly associated with HAPE with Odds Ratio [OR(95%): 1.795(1.018-3.615)(P=0.04)],[OR(95%): 1.732(1.134-2.645)(P=0.011)],[OR(95%): 1.81(1.027-3.193)(P= 0.0038)].Conclusion The rs6194,rs10052957,rs41423247,rs6188 polymorphisms of NR3C1 gene is correlated with HAPE susceptibility.