You are here
Effect of genetic variants associated with plasma homocysteine levels on stroke risk.
Wednesday,2015-03-04 12:18 America/Los_Angeles — zdrager
| Title | Effect of genetic variants associated with plasma homocysteine levels on stroke risk. |
| Publication Type | Journal Article |
| Year of Publication | 2014 |
| Authors | Cotlarciuc, I, Malik, R, Holliday, EG, Ahmadi, KR, Paré, G, Psaty, BM, Fornage, M, Hasan, N, Rinne, PE, Ikram, AM, Markus, HS, Rosand, J, Mitchell, BD, Kittner, SJ, Meschia, JF, van Meurs, JBJ, Uitterlinden, AG, Worrall, BB, Dichgans, M, Sharma, P |
| Corporate/Institutional Authors | METASTROKE and the International Stroke Genetics Consortium |
| Journal | Stroke |
| Volume | 45 |
| Issue | 7 |
| Pagination | 1920-4 |
| Date Published | 2014 Jul |
| ISSN | 1524-4628 |
| Keywords | Brain Ischemia, Cohort Studies, Europe, Genetic Association Studies, Genetic Loci, Genetic Predisposition to Disease, Genetic Variation, Genome, Homocysteine, Humans, Polymorphism, Single Nucleotide, Risk, Stroke |
| Abstract | <p><b>BACKGROUND AND PURPOSE: </b>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.</p><p><b>METHODS: </b>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.</p><p><b>RESULTS: </b>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.</p><p><b>CONCLUSIONS: </b>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.</p> |
| DOI | 10.1161/STROKEAHA.114.005208 |
| Alternate Journal | Stroke |
| PubMed ID | 24846872 |
| PubMed Central ID | PMC4083192 |
| Grant List | / / Medical Research Council / United Kingdom / / Department of Health / United Kingdom P30 DK072488 / DK / NIDDK NIH HHS / United States Z99 OD999999 / / Intramural NIH HHS / United States / / Wellcome Trust / United Kingdom |