Effect of Genetic Variants Associated With Plasma Homocysteine Levels on Stroke Risk Academic Article uri icon

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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.

authors

  • Cotlarciuc, Ioana
  • Malik, Rainer
  • Holliday, Elizabeth G
  • Ahmadi, Kourosh R
  • Pare, Guillaume
  • Psaty, Bruce M
  • Fornage, Myriam
  • Hasan, Nazeeha
  • Rinne, Paul E
  • Ikram, M Arfan
  • Markus, Hugh S
  • Rosand, Jonathan
  • Mitchell, Braxton D
  • Kittner, Steven J
  • Meschia, James F
  • van Meurs, Joyce BJ
  • Uitterlinden, Andre G
  • Worrall, Bradford B
  • Dichgans, Martin
  • Sharma, Pankaj

publication date

  • July 2014

published in