Association Between Genetic Polymorphisms Of HIF-2? Gene And High Altitude Pulmonary Hypertension In Han Population

Objectives: To test the hypothesis that the single nucleotide polymorphisms(SNPs)in HIF-2? gene are associated with the susceptibility to high altitude pulmonary hypertension(HAPH)in Han population in China.To analyze the possible susceptibility genotypes of HIF-2? during HAPH development.Methods: Those who emigrated plateau(average altitude 3 300 m)and have been lived more than 20 years of the Han population as the research object,the method of overall random was used to enroll 49 HAPH patients as the case group(HAPH group)and 39 free of HAPH people as the control group.The Sanger chain termination method was used to detect the SNPs of rs1562453,rs1867785,rs495336,rs7598371,rs11125068,rs7571879,rs10193827,rs13419896,rs2881324,rs7589621,rs4953360,rs7594912,rs11675441,and rs7571218 in HIF-2? gene.Significant locus genotype and 45 cases of Beijing Han genotype in HapMap database were compared,which analysis of three groups of human genetic differences.Results: The genotype and frequencies of rs1562453 were CC(49.0%),CT(46.9%)and TT(4.1%)in the HAPH group,and the locus`s genotype and frequencies were CC(76.9%),CT(17.9%)and TT(5.1%)in the control group.The alleles and frequencies of rs1562453 were C(72.4%)and T(27.6%)in the HAPH group,and the locus`s alleles and frequencies were C(85.9%)and T(14.1%)in the control group.Their genotypes and alleles frequencies were of significant difference between the two groups(genotypes P=0.017;allele P=0.031).Meanwhile,The genotype and frequencies of rs1867785 were AA(46.9%),AG(46.9%)and GG(6.1%)in the HAPH group,and the locus`s genotype and frequencies were AA(74.4%),AG(25.6%)and GG(0.0%)in the control group.The alleles and frequencies of rs1867785 were A(70.4%)and G(29.6%)in the HAPH group,and the locus`s alleles and frequencies were A(87.2%)and G(12.8%)in the control group.Their genotypes and alleles frequencies were of significant difference between the two groups(genotypes P=0.020;allele P=0.008).Genotypes frequencies of the rs1562453 and rs1867785 were analyzed by Logistic Regression show that the genotypes frequencies of rs1562453 was also of significant difference between two groups(Wald= 9.561,P=0.008),CT vs CC(?=1.720,OR=5.580,P =0.011).Their genotypes and alleles frequencies were of significant difference between HAPH group and Beijing Han populations(P<0.001).However,their genotypes and alleles frequencies was nosignificant difference between the control group and the Beijing Han populations(P>0.05).Conclusions: The SNPs of rs1562453 in HIF-2? gene may be associated with the development of HAPH among Chinese Han population,and individuals with the genotype CT may be more vulnerable to HAPH than those who carry with genotype CC,and allele T may be a risk factor for HAPH.A small part of the plateau Han can adapt to the hypoxic environment may be independent of the HIF-2? gene.