ADAMTS-1基因多态性与急性大动脉粥样硬化性脑梗死的相关性

Association of ADAMTS-1 gene polymorphisms with ischemic stroke caused by large artery atherosclerosis

目的探讨含I型血小板结合蛋白基序的解聚蛋白样金属蛋白酶-1（a disintegrin and metalloproteinase with thrombospondin type1 motifs，ADAMTS-1）基因多态性与急性大动脉粥样硬化性脑梗死的关系。方法应用PCR扩增和基因测序法检测767例急性大动脉粥样硬化性脑梗死患者和506名正常对照者的ADAMTSC-1基因5＇-UTR区rs416905（T／C）、rs402007（G／C）位点多态性。结果脑梗死组rs402007位点CC＋GC基因型频率、C等位基因频率高于对照组，差异有统计学意义（68．84％vs．60．67％，x^2=9．012，P=0．003，OR=1．432；45．24％vs．38．54％，x^2=11．208，P=0．001，OR=1．318）；校正危险因素后差异仍具有统计学意义（P=0．001，OR=1．521，95％CI：1．183～1．955）。两组间rs416905位点TC＋CC基因型与rs402007位点GC＋CC基因型频率一致，两位点C等位基因频率一致，经Haploview连锁不平衡分析两位点为完全连锁不平衡（D’=1．0，r^2=1．0）。结论ADAMTS-I基因rs416905、rs402007位点多态性与浙江台州地区汉族人群急性大动脉粥样硬化性脑梗死相关，C等位基因可能是急性大动脉粥样硬化性脑梗死的易感等位基因。

Objective To assess the association of a disintegrin and metallo-proteinase with thrombospondin type 1 motifs （ADAMTS-1）gene polymorphism and ischemic stroke caused by large artery atherosclerosis （LAA）. Methods In total 767 patients and 506 controls were recruited. Single nucleotide polymorphisms （SNPs） rs416905 （T/C） and rs402007 （G/C） of the ADAMTS-1 gene were genotyped by polymerase chain reaction and DNA sequencing. Results Frequencies of the rs402007 GC＋CC genotype and the C allele were significantly different between the two groups （68.84 % vs. 60.67 %, x^2= 9. 012, P= 0.003, OR：. 432; 45. 24% vs. 38. 54%, ;（2：11. 208, P=0. 001, OR=1. 318）. 1Binary logistic regression has confirmed that the above difference was significant （P=0. 001, OR= 1. 521, 95 % CI： 1. 183- 1. 955）. The frequencies of TC＋CC and GC＋CC genotypes were similar between the two groups, and so was it with the C allele. The two SNPs had been in complete linkage disequilibrium （D＇= 1.0, r^2 = 1.0）. Conclusion The rs416905 and rs402007 polymorphisms of the ADAMTS-1 gene may be associated with ischemic stroke caused by LAA. The C allele of the rs402007 locus may be a susceptibility factor for this subtype of stroke.