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Effect of genetic variants associated with plasma homocysteine levels on stroke risk

Cotlarciuc, I, Malik, R, Holliday, EG, Ahmadi, KR, Paré, G, Psaty, BM, Psaty, BM, Fornage, M, Hasan, N, Rinne, PE, Ikram, MA, Markus, HS, Rosand, J, Rosand, J, Rosand, J, Mitchell, BD, Mitchell, BD, Kittner, SJ, Kittner, SJ, Kittner, SJ, Meschia, JF, Van Meurs, JBJ, Uitterlinden, AG, Worrall, BB, Worrall, BB, Dichgans, M, Dichgans, M and Sharma, P (2014) Effect of genetic variants associated with plasma homocysteine levels on stroke risk Stroke, 45 (7). pp. 1920-1924.

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Abstract

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. © 2014 American Heart Association, Inc.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine > Department of Nutritional Sciences
Authors :
AuthorsEmailORCID
Cotlarciuc, IUNSPECIFIEDUNSPECIFIED
Malik, RUNSPECIFIEDUNSPECIFIED
Holliday, EGUNSPECIFIEDUNSPECIFIED
Ahmadi, KRUNSPECIFIEDUNSPECIFIED
Paré, GUNSPECIFIEDUNSPECIFIED
Psaty, BMUNSPECIFIEDUNSPECIFIED
Psaty, BMUNSPECIFIEDUNSPECIFIED
Fornage, MUNSPECIFIEDUNSPECIFIED
Hasan, NUNSPECIFIEDUNSPECIFIED
Rinne, PEUNSPECIFIEDUNSPECIFIED
Ikram, MAUNSPECIFIEDUNSPECIFIED
Markus, HSUNSPECIFIEDUNSPECIFIED
Rosand, JUNSPECIFIEDUNSPECIFIED
Rosand, JUNSPECIFIEDUNSPECIFIED
Rosand, JUNSPECIFIEDUNSPECIFIED
Mitchell, BDUNSPECIFIEDUNSPECIFIED
Mitchell, BDUNSPECIFIEDUNSPECIFIED
Kittner, SJUNSPECIFIEDUNSPECIFIED
Kittner, SJUNSPECIFIEDUNSPECIFIED
Kittner, SJUNSPECIFIEDUNSPECIFIED
Meschia, JFUNSPECIFIEDUNSPECIFIED
Van Meurs, JBJUNSPECIFIEDUNSPECIFIED
Uitterlinden, AGUNSPECIFIEDUNSPECIFIED
Worrall, BBUNSPECIFIEDUNSPECIFIED
Worrall, BBUNSPECIFIEDUNSPECIFIED
Dichgans, MUNSPECIFIEDUNSPECIFIED
Dichgans, MUNSPECIFIEDUNSPECIFIED
Sharma, PUNSPECIFIEDUNSPECIFIED
Date : 1 January 2014
Identification Number : https://doi.org/10.1161/STROKEAHA.114.005208
Depositing User : Symplectic Elements
Date Deposited : 28 Mar 2017 10:55
Last Modified : 28 Mar 2017 10:55
URI: http://epubs.surrey.ac.uk/id/eprint/808572

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