2014
Effect of genetic variants associated with plasma homocysteine levels on stroke risk
Publication
Publication
Stroke , Volume 45 - Issue 7 p. 1920- 1924
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.
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doi.org/10.1161/STROKEAHA.114.005208, hdl.handle.net/1765/60572 | |
Stroke | |
Organisation | Department of Internal Medicine |
Cotlarciuc, I., Malik, R., Holliday, E., Ahmadi, K., Paré, G., Psaty, B., … Sharma, P. (2014). Effect of genetic variants associated with plasma homocysteine levels on stroke risk. Stroke, 45(7), 1920–1924. doi:10.1161/STROKEAHA.114.005208 |