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与日本个体出血性脑卒中相关的遗传变异。

Association of genetic variants with hemorrhagic stroke in Japanese individuals.

机构信息

Department of Cardiovascular Medicine, Inabe General Hospital, Inabe, Japan.

出版信息

Int J Mol Med. 2010 Apr;25(4):649-56. doi: 10.3892/ijmm_00000388.

Abstract

Although genetic epidemiological studies have implicated several genetic variants as risk factors for hemorrhagic stroke, the genetic determinants of this condition remain largely unknown. We examined an association of genetic variants with intracerebral or subarachnoid hemorrhage among Japanese individuals. The study population comprised 4,304 unrelated Japanese individuals, including 377 subjects with intracerebral hemorrhage, 205 subjects with subarachnoid hemorrhage, and 3,722 controls. The 150 polymorphisms examined in the present study were selected by genome-wide association studies of ischemic stroke and myocardial infarction with the use of the GeneChip Human Mapping 500K Array Set. The chi-square test, multivariable logistic regression analysis with adjustment for covariates, as well as a stepwise forward selection procedure revealed that the C->T polymorphism (rs1324694) of ERLIN1, the C->T polymorphism (rs12679196) of TRAPPC9, and the G->T polymorphism (rs16936752) of WNK2 were significantly (P<0.05) associated with the prevalence of intracerebral hemorrhage, and that the A->G polymorphism (rs3111754) of ITM2C and the A->G polymorphism (rs10986769) of MAPKAP1 were significantly associated with the prevalence of subarachnoid hemorrhage. Genotypes for ERLIN1, TRAPPC9, and WNK2 may prove informative for assessment of the genetic risk for intracerebral hemorrhage, and those for ITM2C and MAPKAP1 may be beneficial in assessment of the genetic risk for subarachnoid hemorrhage in Japanese individuals.

摘要

虽然遗传流行病学研究表明,一些遗传变异是出血性中风的风险因素,但这种疾病的遗传决定因素在很大程度上仍然未知。我们研究了遗传变异与日本人群中颅内或蛛网膜下腔出血之间的关联。研究人群包括 4304 名无血缘关系的日本个体,其中 377 名患者为颅内出血,205 名患者为蛛网膜下腔出血,3722 名对照者。本研究中检查的 150 个多态性是通过使用基因芯片人类映射 500K 阵列集对缺血性中风和心肌梗死的全基因组关联研究选择的。卡方检验、多变量逻辑回归分析调整协变量以及逐步向前选择程序显示,ERLIN1 的 C->T 多态性(rs1324694)、TRAPPC9 的 C->T 多态性(rs12679196)和 WNK2 的 G->T 多态性(rs16936752)与颅内出血的患病率显著相关(P<0.05),ITM2C 的 A->G 多态性(rs3111754)和 MAPKAP1 的 A->G 多态性(rs10986769)与蛛网膜下腔出血的患病率显著相关。ERLIN1、TRAPPC9 和 WNK2 的基因型可能对评估颅内出血的遗传风险有帮助,而 ITM2C 和 MAPKAP1 的基因型可能有助于评估日本人群蛛网膜下腔出血的遗传风险。

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