中华医学杂志
中華醫學雜誌
중화의학잡지
National Medical Journal of China
2009年
22期
1536-1539
,共4页
张伟丽%孙凯%汪一波%郑翼%万鲁红%秦勤%汪道文%廖玉华%马爱群%祝之明%惠汝太
張偉麗%孫凱%汪一波%鄭翼%萬魯紅%秦勤%汪道文%廖玉華%馬愛群%祝之明%惠汝太
장위려%손개%왕일파%정익%만로홍%진근%왕도문%료옥화%마애군%축지명%혜여태
脑卒中%内皮%血管%内皮生长因子%变异(遗传学)
腦卒中%內皮%血管%內皮生長因子%變異(遺傳學)
뇌졸중%내피%혈관%내피생장인자%변이(유전학)
Genetics%Endothelium,vascular%Endothelial growth factors%Uariation (genetics)
目的 探讨血管内皮细胞生长因子受体(VEGFR-2)基因的编码区变异对受体功能的影响及与脑卒中患病风险的关系.方法 利用多中心病例-对照研究,在1849例脑卒中患者(血栓形成性脑梗死812例,腔隙性脑梗死530例,脑出血507例)和1798例对照人群中检测VEGFR-2基因编码区变异rs2305948(Val297Ile)与脑卒中易感性的关联,并在另一个独立的病例-对照研究(327例脑卒中和327例对照)中进行验证.放射性受体配体结合实验测定基因变异对VEGFR-2与配基VEGF亲和能力的改变.结果 VEGFR-2基因变异297Ile携带者频率在脑出血组显著高于对照组[脑出血组:Val/Ile,155(30.6%);Ile/Ile,16(3.2%);对照组:Val/Ile,351(19.5%);He/Ile,18(1.0%);P<0.01],与脑出血的高发病风险相关(OR 2.25;95% CI 1.70～2.96;P<0.01),验证研究亦得到相似结果.常见等位基因297Val被替换为297Ile时,VEGFR-2与配基VEGF的平衡解离常数显著增加[分别为(87±9)pmol/L和(195±36)pmol/L,P<0.01].结论 VEGFR-2基因变异297Ile降低该受体与配基的亲和能力,并与脑出血的高发病风险相关.其分子机制可能是由于VEGF/VEGFR-2信号通路下调,引起血管内皮细胞的稳态和完整性受损,在血压升高等情况下导致血管易破裂、出血.
目的 探討血管內皮細胞生長因子受體(VEGFR-2)基因的編碼區變異對受體功能的影響及與腦卒中患病風險的關繫.方法 利用多中心病例-對照研究,在1849例腦卒中患者(血栓形成性腦梗死812例,腔隙性腦梗死530例,腦齣血507例)和1798例對照人群中檢測VEGFR-2基因編碼區變異rs2305948(Val297Ile)與腦卒中易感性的關聯,併在另一箇獨立的病例-對照研究(327例腦卒中和327例對照)中進行驗證.放射性受體配體結閤實驗測定基因變異對VEGFR-2與配基VEGF親和能力的改變.結果 VEGFR-2基因變異297Ile攜帶者頻率在腦齣血組顯著高于對照組[腦齣血組:Val/Ile,155(30.6%);Ile/Ile,16(3.2%);對照組:Val/Ile,351(19.5%);He/Ile,18(1.0%);P<0.01],與腦齣血的高髮病風險相關(OR 2.25;95% CI 1.70～2.96;P<0.01),驗證研究亦得到相似結果.常見等位基因297Val被替換為297Ile時,VEGFR-2與配基VEGF的平衡解離常數顯著增加[分彆為(87±9)pmol/L和(195±36)pmol/L,P<0.01].結論 VEGFR-2基因變異297Ile降低該受體與配基的親和能力,併與腦齣血的高髮病風險相關.其分子機製可能是由于VEGF/VEGFR-2信號通路下調,引起血管內皮細胞的穩態和完整性受損,在血壓升高等情況下導緻血管易破裂、齣血.
목적 탐토혈관내피세포생장인자수체(VEGFR-2)기인적편마구변이대수체공능적영향급여뇌졸중환병풍험적관계.방법 이용다중심병례-대조연구,재1849례뇌졸중환자(혈전형성성뇌경사812례,강극성뇌경사530례,뇌출혈507례)화1798례대조인군중검측VEGFR-2기인편마구변이rs2305948(Val297Ile)여뇌졸중역감성적관련,병재령일개독립적병례-대조연구(327례뇌졸중화327례대조)중진행험증.방사성수체배체결합실험측정기인변이대VEGFR-2여배기VEGF친화능력적개변.결과 VEGFR-2기인변이297Ile휴대자빈솔재뇌출혈조현저고우대조조[뇌출혈조:Val/Ile,155(30.6%);Ile/Ile,16(3.2%);대조조:Val/Ile,351(19.5%);He/Ile,18(1.0%);P<0.01],여뇌출혈적고발병풍험상관(OR 2.25;95% CI 1.70～2.96;P<0.01),험증연구역득도상사결과.상견등위기인297Val피체환위297Ile시,VEGFR-2여배기VEGF적평형해리상수현저증가[분별위(87±9)pmol/L화(195±36)pmol/L,P<0.01].결론 VEGFR-2기인변이297Ile강저해수체여배기적친화능력,병여뇌출혈적고발병풍험상관.기분자궤제가능시유우VEGF/VEGFR-2신호통로하조,인기혈관내피세포적은태화완정성수손,재혈압승고등정황하도치혈관역파렬、출혈.
Objective To assess whether variants in the vascular endothelial growth actor receptor 2 (VEGFR-2) gene confer susceptibility to stroke risk. Methods Association between gene variant rs2305948 (Val297Ile) and the risk of stroke was investigated in a multi-center case-control study, which comprised of 1849 patients with stroke (812 cerebral atherothrombosis, 530 lacunar infarction, and 507 intracerebral hemorrhage) and 1798 controls, and then replicated in the second independent stroke study (327 cases and 327 controls). The effect of Val297Ile on the binding ability of VEGFR-2 to VEGF was determined by a radioligand binding assay. Results The frequencies of carriers with variant 297Ile were significantly higher in patients with hemorrhagic stroke than in controls [297Val/Ile: 155 (30.6%) versus 351(19.5% ), 297Ile/Ile: 18 (3.2%) versus 16 (1.0%); P<0.01]. The variant 297Ile was significantly associated with increased risk of hemorrhagic stroke (odds ratio 2.25, 95% confidence interval 1.70-2.96; P<0.01), and replication in the second stroke study obtained similar results. The substitution of Val to Ile at the amino acid residue 297 led to an increased equilibrium dissolved constant between VEGF and its receptor VEGFR-2 [297Val (87±9) pmol/L versus 297Ile (195±36) pmol/L, P<0.01]. Conclusions The VEGFR-2 gene variants may serve as novel genetic markers for the risk of hemorrhagic stroke.
