TIMP-3启动子区-1296T／C、-915A／G基因多态性与汉族人群动脉粥样硬化性脑梗塞的关联分析  

Association between -1296T/C and -915A/G polymorphisms of matrix metalloproteinase inhibitor-3 gene and atherosclerotic cerebral infarction in an ethnic Han Chinese population

作　　者：郑周[1] 金笑平[1] 朱敏 李彩[1] 朱峰[1] 李卫玲[1] 林青[1] 王凤[1] 王皖芬[1] 胡晓飞[1] 吕晨玲 

机构地区：[1]浙江省温州医科大学附属台州医院神经内科,317000 [2]公共实验平台

出　　处：《中华医学遗传学杂志》2014年第6期719-724,共6页Chinese Journal of Medical Genetics

基　　金：浙江省自然科学基金（LY13h290003）;浙江省中医药科学研究基金（2011ZAlll）

摘　　要：目的探讨基质金属蛋白酶抑制剂-3 （tissue inhibitor of metalloproteinase-3, TIMP-3）基因启动子区-1296T／C、-915A／G位点基因多态性与动脉粥样硬化性脑梗塞的关系。方法对485例动脉粥样硬化性脑梗塞和525名健康体检者进行研究，采用DNA直接测序法分析TIMP-3基因启动子区-1296T／C、-915A／G多态性，同时用ELISA法测定血清TIMP-3水平。结果脑梗塞组和健康对照组之间基因型和等位基因频率比较差异均有统计学意义（X^2=5．227和5．869，P值为0．022和0．015），-1296T／C与-915A／G之间存在完全连锁不平衡关系（D’=1．0，r2=0．991）。脑梗塞组患者48h内血清TIMP-3为（248．90±97．10）pg／mL，对照组为（200．17±79．70）pg／mL，两组比较差别有统计学意义（t=2．098，P=0．039）。结论TIMP-3基因启动子区-1296T／C、-915A／G两位点存在连锁不平衡关系，且两位点的多态性与中国汉族人群动脉粥样硬化性脑梗塞遗传易感性有关，TIMP-3基因多态性可能是中国人群动脉粥样硬化性脑梗塞高危人群筛选的标志和干预靶点。Objective To assess the association between -1296T/C and -915A/G polymorphisms in the promoter region of matrix metalloproteinase inhibitor-3 gene （TIMP-3）and atherosclerotic cerebral infarction in an ethnic Han Chinese population. Methods Peripheral blood samples were collected from 485 patients with atherosclerotic cerebral infarction and 525 healthy controls. Serum levels of TIMP-3 were measured with an enzyme-linked immunosorbent assay （ELISA）. The polymorphisms of the TIMP-3 gene were analyzed with DNA sequencing. Results There were significant differences in genotype and allele frequencies in --1296T/C and --915A/G between the patients and healthy controls （X2= 5. 227 and 5. 869, P：0. 022 and 0. 015, respectively）. Besides, there was a strong linkage disequilibrium between -1296T/C and -915A/G （D＇= 1.0, r2= 0. 991）. The serum levels of TIMP-3 in patients were significantly higher than the control group E（248.90±97.10） pg/mL vs. （200.17 4- 79.70） pg/mL, t=2. 098, P=0. 039]. Conclusion The --1296T/C and -915A/G polymorphisms of the TIMP-3 gene are associated with increased risk for atherosclerotic cerebral infarction in ethnic Han Chinese and may be used as molecular markers for the disease. There is also strong linkage disequilibrium between the two loci.

关 键 词：基质金属蛋白酶抑制剂3 单核苷酸多态性 连锁不平衡 脑梗塞 

分 类 号：R743[医药卫生—神经病学与精神病学]