title: Low density lipoprotein receptor related protein 1 and 6 gene variants and ischaemic stroke risk.
abstract: OBJECTIVE
  Low density lipoprotein receptor related proteins (LRPs) 1 and 6 have been implicated in cerebral ischaemia. In addition, genetic variation in LRP1 and LRP6 has been linked with various factors that are related to risk of ischaemic stroke. The aim of this study was to examine the association of LRP1 and LRP6 gene variants with risk of ischaemic stroke as part of the Ischemic Stroke Genetics Study (ISGS).
  
  
  METHODS
  A Caucasian series (434 stroke patients, 319 controls) and an African American series (161 stroke patients, 116 controls) were included. Fourteen LRP6 variants and three LRP1 variants were genotyped and assessed for association with ischaemic stroke.
  
  
  RESULTS
  In the Caucasian series, significant associations with ischaemic stroke were observed for LRP6 rs2075241 [odds ratio (OR) 0.42, P = 0.023], rs2302685 (OR 0.44, P = 0.049), rs7975614 (OR 0.07, P = 0.017), rs10492120 (OR 0.62, P = 0.036) and rs10743980 (OR 0.66, P = 0.037). Risk of ischaemic stroke was significantly lower for carriers of any of these five protective LRP6 variants (24.0% of subjects) compared to non-carriers (OR 0.57, P = 0.003). The protective association for LRP6 rs2075241 was observed at a similar magnitude across ischaemic stroke subtypes, whilst the effects of rs23022685, rs10492120 and rs10743980 were most apparent for cardioembolic and large vessel stroke. In the African American series, LRP1 rs11172113 was associated with an increased risk of stroke (OR 1.89, P = 0.006).
  
  
  CONCLUSIONS
  The results of our preliminary study provide evidence that LRP6 and LRP1 variants may be associated with risk of ischaemic stroke. Validation in larger studies is warranted.
authors.affiliation: Department of Neurology, Mayo Clinic Florida, Jacksonville, FL, USA.|Department of Neuroscience, Mayo Clinic Florida, Jacksonville, FL, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Harriott
authors.affiliation: Division of Biomedical Statistics and Informatics, Mayo Clinic Florida, Jacksonville, FL, USA.
authors.forename: M G
authors.initials: MG
authors.lastname: Heckman
authors.affiliation: Department of Neuroscience, Mayo Clinic Florida, Jacksonville, FL, USA.
authors.forename: S
authors.initials: S
authors.lastname: Rayaprolu
authors.affiliation: Department of Neuroscience, Mayo Clinic Florida, Jacksonville, FL, USA.
authors.forename: A I
authors.initials: AI
authors.lastname: Soto-Ortolaza
authors.affiliation: Division of Biomedical Statistics and Informatics, Mayo Clinic Florida, Jacksonville, FL, USA.
authors.forename: N N
authors.initials: NN
authors.lastname: Diehl
authors.affiliation: Department of Neuroscience, Mayo Clinic Florida, Jacksonville, FL, USA.
authors.forename: T
authors.initials: T
authors.lastname: Kanekiyo
authors.affiliation: Department of Neuroscience, Mayo Clinic Florida, Jacksonville, FL, USA.
authors.forename: C-C
authors.initials: CC
authors.lastname: Liu
authors.affiliation: Department of Neuroscience, Mayo Clinic Florida, Jacksonville, FL, USA.
authors.forename: G
authors.initials: G
authors.lastname: Bu
authors.affiliation: Institute for Stroke and Dementia Research, Ludwig-Maximilians-Universität, München, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Malik
authors.affiliation: Department of Neurology, University of Maryland Medical Center and Baltimore Veterans Affairs Medical Center, Baltimore, MD, USA.
authors.forename: J W
authors.initials: JW
authors.lastname: Cole
authors.affiliation: Department of Neurology, Mayo Clinic Florida, Jacksonville, FL, USA.
authors.forename: J F
authors.initials: JF
authors.lastname: Meschia
authors.affiliation: Department of Neuroscience, Mayo Clinic Florida, Jacksonville, FL, USA.
authors.forename: O A
authors.initials: OA
authors.lastname: Ross
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D002545:Brain Ischemia / Q000235:genetics*; D005260:Female; D006801:Humans; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000235:genetics*; D060488:Low Density Lipoprotein Receptor-Related Protein-6 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020521:Stroke / Q000235:genetics*; D044465:White People / Q000235:genetics*; D055815:Young Adult
chemical_list: D026503:Low Density Lipoprotein Receptor-Related Protein-1; D060488:Low Density Lipoprotein Receptor-Related Protein-6
keywords: genetics; ischaemic stroke; low density lipoprotein receptor related protein