Effect of genetic variants associated with plasma homocysteine levels on stroke risk.
Effect of genetic variants associated with plasma homocysteine levels on stroke risk.
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DOI：
10.1161/strokeaha.114.005208
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发表时间：
2014-07
期刊：
影响因子：
8.3
通讯作者：
METASTROKE and the International Stroke Genetics Consortium
中科院分区：
文献类型：
--
作者：
Cotlarciuc I;Malik R;Holliday EG;Ahmadi KR;Paré G;Psaty BM;Fornage M;Hasan N;Rinne PE;Ikram MA;Markus HS;Rosand J;Mitchell BD;Kittner SJ;Meschia JF;van Meurs JB;Uitterlinden AG;Worrall BB;Dichgans M;Sharma P;METASTROKE and the International Stroke Genetics Consortium
已知同型半胱氨酸(THcy)水平升高与缺血性中风(IS)风险增加有关。鉴于tHcy和IS都是可遗传的特征，我们通过评估18个先前与tHcy水平相关的多态与IS及其亚型的关系，调查了同型半胱氨酸水平与卒中风险之间的潜在遗传关系。先前来自国际卒中协作网络MetaStroke的荟萃分析结果被用来评估12,389例IS患者和62,004名对照中18个tHcy相关SNP的相关性。我们还调查了位于18个tHcy相关SNPs 50kb以内区域的关联性，以及包括这18个SNPs在内的遗传风险分数的关联性。在校正多次检测后，位于RASIP1基因的一个SNP和位于SLC17A3及其附近的三个SNP与IS(P<；0.0003)显著相关。在卒中亚型中，位于MUT上游的SNP与小血管病变显著相关(P=0.0022)，而位于MTHFR的1个SNP与大血管病变显著相关(P=0.00019)。包括18个SNP的遗传风险得分与IS或其亚型没有显示出显著的关联。这项研究发现了几种潜在的与IS及其亚型的关联：MUT变异与SVD的关联，MTHFR变异与LVD的关联，以及RASIP1和SLC17A3变异与整体IS的关联。
Elevated homocysteine (tHcy) levels are known to be associated with increased risk of ischemic stroke (IS). Given that both tHcy and IS are heritable traits, we investigated a potential genetic relationship between homocysteine levels and stroke risk by assessing 18 polymorphisms previously associated with tHcy levels for their association with IS and its subtypes. Previous meta-analysis results from an international stroke collaborative network, METASTROKE, were utilized to assess association of the 18 tHcy associated SNPs in 12,389 IS cases and 62,004 controls. We also investigated the associations in regions located within 50kb from the 18 tHcy related SNPs, and the association of a genetic risk score including the 18 SNPs. One SNP located in the RASIP1 gene and a cluster of three SNPs located at and near SLC17A3 were significantly associated with IS (P<0.0003) after correcting for multiple testing. For stroke subtypes, the sentinel SNP located upstream of MUT was significantly associated with SVD (small vessel disease) (P=0.0022), while one SNP located in MTHFR was significantly associated with LVD (large vessel disease) (P=0.00019). A genetic risk score including the 18 SNPs did not show significant association with IS or its subtypes. This study found several potential associations with IS and its subtypes: an association of an MUT variant with SVD, an MTHFR variant with LVD, and associations of RASIP1 and SLC17A3 variants with overall IS.