上海地区汉族人群抗凝血酶基因多态性与肺血栓栓塞症风险的相关性研究

Research of correlation between antithrombin gene polymorphism and risk of pulmonary thromboembolism in Han people of Shanghai

目的探讨上海地区汉族人群抗凝血酶（antithrombin，AT）基因多态性与肺血栓栓塞症（pulmonary thromboembolism，PTE）风险的相关性。方法采用病例对照研究的方法，选取91例上海地区汉族PTE患者作为病例组和87例上海汉族体检健康者作为对照组。通过对AT基因的外显子I的5’端前核苷酸序列-150～＋68及内含子I中核苷酸序列＋300～＋700进行测序，测得2个多态性位点，分别为＋320C／T和＋645G／A。运用聚合酶链反应一限制性内切酶片段长度多态性技术检测上述2个位点的基因型，并利用SHEsis软件构建其单倍体型，进行单倍体型与PTE风险关联的统计学分析。结果①研究发现上海地区汉族人群AT基因2个单核苷酸多态性位点的基因型频率及等位基因频率PTE组与对照组之间差异无统计学意义。②研究发现上海地区汉族人群AT基因共有4种单倍体型CA、CG、TA、TG，这4种单倍体型频率在PTE组分别为51．26（28．2％）、71．74（39．4％）、1．74（1．0％）、57．26（31．5％）；对照组分别为59．00（33．9％）、68．00（39．1％）、0．00（0．0％）、47．00（27．0％），PTE组与对照组单倍型频率差异无统计学意义。D’〉0．9，上海地区汉族人群AT基因2个多态性位点间存在高度连锁不平衡。结论上海地区汉族人群AT基因多态性位点与PTE易感性不存在明显相关，AT基因2个位点多态性不是上海地区人群PTE发病的高危因素。

Objective To investigate the correlation between antithrombin AT） gene polymorphism and risk of pulmonary thromboembolism （PTE）in Han people of Shanghai. Methods A case control study was adopted. Ninty-one Han patients with PTE in Shanghai were selected as a case group and eighty-seven Han healthy people in Shanghai were selected as a control group. Two polymorphisms （＋320C/T and＋ 645G/A） were found by sequencing the upstream of the first exon （-150/＋ 68 nucleotides） and the first intron （＋ 300/＋ 700 nucleotides） of AT gene. The genotypes were identified by polymerase chain reaction-restriction fragment length polymorphism. The genotype and allele frequencies, the D＇ value between two single nucleotide polymorphisms sites, the haplotype and their frequencies were analyzed respectively. Results （1） The results suggested that there was no statistical difference on the distribution of genotype and allelic frequencies between PTE group and control group in Han people of Shanghai. （2）The four haplotypes were CA,CG,TA and TG in Han people of Shanghai. The haplotype frequencies were 51.26 （28.2%）,71.74 （39.4%）,1.74 （1. 0%） , 57. 26 （31.5%） in PTE group,and were 59.00 （33.9%）,68.00 （39.1%） ,0.00 （0.0%） ,47.00 （27.0%） in control group. There was no statistical difference on haplotype frequencies between PTE group and control group. D＇〉 0.9.There was strong linkage disequilibrium between the two single nucleotide polymorphism sites of AT gene in Han people of Shanghai. Conclusions There is no obvious correlation between the polymorphism of AT gene and the susceptibility to PTE in Han people of Shanghai. The polymorphism of two sites is not the high risk factor of PTE in Han people of Shanghai.