摘要目的 探讨低氧诱导因子2α(HIF-2α)基因多态性与汉族高原肺动脉高压(HAPH)的关联性.方法 以移居高原(平均海拔3300m)且居住20年以上的汉族人群为研究对象,整群随机抽样收集49例HAPH患者为试验组(HAPH组)和39名非HAPH个体(均无呼吸及心脏疾病)为对照组.采用Sanger基因测序方法,测定所有对象HIF-2α基因5个位点(rs1562453、rs1867785、rs4953361、rs7598371、rs11125068)的基因型和等位基因,分析各位点基因型及等位基因的分布在两组间的差异.结果 HAPH组与对照组位点rs1562453三种基因型均为CC、CT、TT,其频率分别为49.0％、46.9％、4.1％比76.9％、17.9％、5.1％;等位基因为C和T,其频率分别为72.4％、27.6％比85.9％、14.1％;基因型及等位基因在组间差异均有统计学意义(基因型:P =0.017,等位基因:P=0.031).HAPH组与对照组位点rs1867785三种基因型均为AA、AG、GG,其频率分别为46.9％、46.9％、6.1％比74.4％、25.6％、0.0％;等位基因为A和G,其频率为70.4％、29.6％比87.2％、12.8％;基因型及等位基因在组间差异均有统计学意义(基因型:P=0.020,等位基因:P =0.008).Logistic回归分析结果显示,位点rs1562453三种基因型分布在两组间差异仍有统计学意义(Wald=9.561,P=0.008),CT比CC(β=1.720,OR=5.580,P=0.011).结论 HIF-2α位点rs1562453基因多态性可能与汉族HAPH遗传易感性相关,基因型为CT个体患HAPH的风险较CC人群高,等位基因T可能是HAPH的危险等位基因.

abstractsObjective To test the hypothesis that the single nucleotide polymorphisms (SNPs) in HIF-2o gene were associated with the susceptibility of high altitude pulmonary hypertension (HAPH) in Han population in China.Methods Those Han population who emigrated to plateau (average altitude 3 300 m) and have been lived here for more than 20 years were included as the research subjects,the method of cluster random sampling 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,rs4953361,rs7598371 and rs11125068 in HIF-2α gene.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 which showed that the genotypes frequencies of rs1562453 were also of significant difference between two groups (Wald =9.561,P=0.008),CT vs CC (3 =1.720,OR =5.580,P =0.011).Conclusion The SNPs of rs1562453 in HIF-2o 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 genotype CC,and allele T may be a risk factor for HAPH.