Low density lipoprotein receptor related protein 1 and 6 gene variants and ischaemic stroke risk. (29th May 2015)

• Record Type: Journal Article
• Authors: Harriott, A. M.; Heckman, M. G.; Rayaprolu, S.; Soto‐Ortolaza, A. I.; Diehl, N. N.; Kanekiyo, T.; Liu, C.‐C.; Bu, G.; Malik, R.; the METASTROKE Consortium; Cole, J. W.; Meschia, J. F.; Ross, O. A.
• Is Part Of: European journal of neurology. Volume 22:Number 8(2015:Aug.)
• Page Start: 1235
• Page End: 1241
• Publication Date: 2015-05-29
• Subjects: Neurology -- Periodicals; Nervous system -- Diseases -- Periodicals; 616.8
• DOI: 10.1111/ene.12735
• Languages: English
• ISSNs: 1351-5101

Abstract

<abstract abstract-type="main" id="ene12735-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="ene12735-sec-0001" sec-type="section"> <title>Background and purpose</title> <p>Low density lipoprotein receptor related proteins (LRPs) 1 and 6 have been implicated in cerebral ischaemia. In addition, genetic variation in <italic>LRP1</italic> and <italic>LRP6</italic> 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 <italic>LRP1</italic> and <italic>LRP6</italic> gene variants with risk of ischaemic stroke as part of the Ischemic Stroke Genetics Study (ISGS).</p> </sec> <sec id="ene12735-sec-0002" sec-type="section"> <title>Methods</title> <p>A Caucasian series (434 stroke patients, 319 controls) and an African American series (161 stroke patients, 116 controls) were included. Fourteen <italic>LRP6</italic> variants and three <italic>LRP1</italic> variants were genotyped and assessed for association with ischaemic stroke.</p> </sec> <sec id="ene12735-sec-0003" sec-type="section"> <title>Results</title> <p>In the Caucasian series, significant associations with ischaemic stroke were observed for <italic>LRP6</italic> rs2075241 [odds ratio (OR) 0.42, <italic>P</italic> = 0.023], rs2302685 (OR 0.44, <italic>P</italic> = 0.049), rs7975614 (OR 0.07, <italic>P</italic> = 0.017), rs10492120 (OR 0.62, <italic>P</italic> = 0.036) and rs10743980 (OR 0.66, <italic>P</italic> = 0.037). Risk of ischaemic stroke was significantly lower for carriers of any of these five protective <italic>LRP6</italic> variants (24.0% of subjects) compared to non‐carriers (OR 0.57, <italic>P</italic> = 0.003). The protective association for <italic>LRP6</italic> 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, <italic>LRP1</italic> rs11172113 was associated with an increased risk of stroke (OR 1.89, <italic>P</italic> = 0.006).</p> </sec> <sec id="ene12735-sec-0004" sec-type="section"> <title>Conclusions</title> <p>The results of our preliminary study provide evidence that <italic>LRP6</italic> and <italic>LRP1</italic> variants may be associated with risk of ischaemic stroke. Validation in larger studies is warranted.</p> </sec> </abstract>