摘要目的 探讨含Ⅰ型血小板反应蛋白的解聚素和金属蛋白酶-12 (a disintegrin and metalloproteinase with thrombospondin motifs 12,ADAMTS-12)基因多态性与急性大动脉粥样硬化(large artery atherosclerotic,LAA)型脑梗死的关系.方法 连续收集2012年1月至2015年1月在浙江省台州医院神经内科首次因脑梗死住院的患者396例及同期健康体检者318名.应用基因测序法测定ADAMTS-12基因rs25754(T/C)、rs6865176 (A/G)、rs79110681(A/G)、rs185365 (T/G)、rs457353(A/C)多态性.结果 rs25754、rs185365和rs457353位点两两之间分别存在完全连锁不平衡(D'=1.0,r2=1.0).rs25754等位基因T在脑梗死组和对照组中分布频率分别为82.2％和77.5％,差异具有统计学意义(x2=4.852,P=0.028),且脑梗死组中(TT +TC)基因型多于对照组(x2=5.000,P=0.025).rs185365等位基因T分布频率在脑梗死组中为82.2％,高于对照组的77.5％,差异具有统计学意义(x2=4.852,P=0.028),且脑梗死组中(TT+TG)基因型多于对照组(x2=5.000,P=0.025).rs457353等位基因A在脑梗死组和对照组中分布频率分别为82.2％和77.5％,差异具有统计学意义(x2=4.852,P=0.028),且脑梗死组中(AA+ AC)基因型多于对照组(x2 =5.000,P=0.025).rs6865176和rs79110681等位基因频率和基因型在两组间差异无统计学意义.单倍体分析中,单倍体型(T-T-A)的OR值为1.339(x2=4.852,P=0.028),单倍体型(C-G-C)的OR值为0.747(x2=4.852,P=0.028).结论 rs25754、rs185365、rs457353基因多态性与浙江省南部地区急性LAA型脑梗死相关.单倍体型(T-T-A)可作为脑梗死高危人群的筛选标志.

abstractsObjective To investigate the relationship between gene polymorphism of a disintegrin and metalloproteinase with thrombospondin motifs-12 (ADAMTS-12) and acute cerebral infarction of large artery atherosclemsis (LAA) in Han Chinese population in southern Zhejiang region.Methods Three hundred and ninety-six cerebral infarct patients with first onset and 318 controls were included in the study.The polymorphisms of ADAMTS-12 gene were detected by DNA sequencing.Results Among rs25754,rs185365 and rs457353,there were complete linkage disequilibrium (D' =1.0,r2 =1.0).The T allele of rs25754 was higher in case group than that in control group (82.2％ vs 77.5％,x2 =4.852,P =0.028).The number of (TT + TC) genotype in case group is more than control group (x2 =5.000,P =0.025).What's more,the T allele of rs185365 was higher in case group than that in control group (82.2％ vs 77.5％,x2 =4.852,P =0.028).The number of (TT + TG) genotype in case group is more than control group(x2 =5.000,P =0.025).The A allele of rs457353 was higher in case group than that in control group (82.2％ vs 77.5％,x2 =4.852,P =0.028).The number of (AA + AC) genotype in case group is more than control group (x2 =5.000,P =0.025).No significant difference was found in the allele frequencies and genotypes of rs6865176 and rs79110681 between case and control groups.In the analysis of haplotype,the OR value of haplotype (T-T-A) was 1.339 (x2 =4.852,P =0.028),while the OR value of haplotye (C-G-C) was 0.747 (x2 =4.852,P =0.028).Conclusions Acute cerebral infarction with LAA is associated with rs25754,rs185365 and rs457353 gene polymorphisms,while not associated with rs6865176 and rs79110681 gene polymorphisms in Han Chinese population in southern zhejiang region.Haplotype (T-T-A) could be applied as a candidate biomarker for screening patients with high risk of cerebral infarction.