- Title
- Effect of genetic variants associated with plasma homocysteine levels on stroke risk
- Creator
- Cotlarciuc, Iona; Malik, Rainer; Markus, Hugh S.; Rosand, Jonathan; Mitchell, Braxton D.; Kittner, Steven J.; Meschia, James F.; van Meurs, Joyce B. J.; Uitterlinden, Andre G.; Worrall, Bradford B.; Dichgans, Martin; Sharma, Pankaj; Holliday, Elizabeth G.; Ahmadi, Kourosh R.; Paré, Guillaume; Psaty, Bruce M.; Fornage, Myriam; Hasan, Nazeeha; Rinne, Paul E.; Ikram, M. Arfan
- Relation
- Stroke Vol. 45, Issue 7, p. 1920-1924
- Publisher Link
- http://dx.doi.org/10.1161/STROKEAHA.114.005208
- Publisher
- Lippincott Williams & Wilkins
- Resource Type
- journal article
- Date
- 2014
- Description
- Background and Purpose: Elevated total plasma 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. Methods: Previous meta-analysis results from an international stroke collaborative network, METASTROKE, were used to assess association of the 18 tHcy-associated single-nucleotide polymorphisms (SNPs) in 12 389 IS cases and 62 004 controls. We also investigated the associations in regions located within 50 kb from the 18 tHcy-related SNPs and the association of a genetic risk score, including the 18 SNPs. Results: One SNP located in the RASIP1 gene and a cluster of 3 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 small-vessel disease (P=0.0022), whereas 1 SNP located in MTHFR was significantly associated with large-vessel disease (P=0.00019). A genetic risk score, including the 18 SNPs, did not show significant association with IS or its subtypes. Conclusions: This study found several potential associations with IS and its subtypes: An association of an MUT variant with small-vessel disease, an MTHFR variant with large-vessel disease, and associations of RASIP1 and SLC17A3 variants with overall IS.
- Subject
- genetic association studies; genetic risk score; homocysteine; stroke
- Identifier
- http://hdl.handle.net/1959.13/1303198
- Identifier
- uon:20633
- Identifier
- ISSN:0039-2499
- Language
- eng
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