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Two Novel SNPs in the PLCL2 Gene Associated with Large Artery Atherosclerotic Stroke Identified by Fine-Mapping

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A genome-wide association study (GWAS) reported that the single nucleotide polymorphism (SNP) rs4618210 in the PLCL2 gene is related to myocardial infarction (MI) in the Japanese population, but no study has examined the correlation of PLCL2 with ischemic stroke (IS). The present study was designed to investigate whether the genetic variation in PLCL2 is associated with large artery atherosclerotic (LAA) stroke in a Han Chinese population. Tagging SNPs (tSNPs) of the PLCL2 gene were determined by a fine-mapping strategy and were genotyped by improved multiplex ligation detection reaction (iMLDR) technology in 669 LAA stroke patients and 668 healthy controls. A logistic regression model was used to analyze the associations between genetic variation at PLCL2 and the risk of LAA stroke. Two SNPs were significantly associated with the risk of LAA stroke after adjusting for potential confounders: for rs4685423, the AA genotype and CA genotype decreased the risk of LAA stroke compared with the CC genotype (multivariate-adjusted, P = 0.001); for rs4618210, the AA genotype and GA genotype decreased the risk of LAA stroke compared with the GG genotype (multivariate-adjusted, P = 0.007). In addition, haplotype analysis indicated that compared with haplotype TTT, haplotype TAT decreased the risk of LAA stroke in block 2 (adjusted OR, 0.706; 95% CI, 0.550–0.907; P = 0.006). The analysis of SNP–SNP interactions showed that rs4685423 was the most influential contributor to LAA stroke risk. SNPs rs4685423 and rs4618210 in the PLCL2 gene may be related to the risk of LAA stroke in Han Chinese.

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  • Adams HJ, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL et al (1993) Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke 24(1):35–41

    Article  Google Scholar 

  • Bak S, Gaist D, Sindrup SH, Skytthe A, Christensen K (2002) Genetic liability in stroke: a long-term follow-up study of Danish twins. Stroke 33(3):769–774

    Article  Google Scholar 

  • Bevan S, Traylor M, Adib-Samii P, Malik R, Paul NL, Jackson C et al (2012) Genetic heritability of ischemic stroke and the contribution of previously reported candidate gene and genomewide associations. Stroke 43(12):3161–3167

    Article  CAS  Google Scholar 

  • Cai C, Xiao R, Van Halm-Lutterodt N, Zhen J, Huang X, Xu Y, et al (2016) Association of MTHFR, SLC19A1 genetic polymorphism, serum folate, vitamin B12 and Hcy status with cognitive functions in Chinese adults. Nutrients 8(10).

    Article  Google Scholar 

  • Chauhan G, Debette S (2016) Genetic risk factors for ischemic and hemorrhagic stroke. Curr Cardiol Rep 18(12):124

    Article  Google Scholar 

  • Chen B, Gu T, Ma B, Zheng G, Ke B, Zhang X et al (2014) The CRHR1 gene contributes to genetic susceptibility of aggressive behavior towards others in Chinese southwest Han population. J Mol Neurosci 52(4):481–486

    Article  CAS  Google Scholar 

  • Dichgans M (2007) Genetics of ischaemic stroke. Lancet Neurol 6(2):149–161

    Article  CAS  Google Scholar 

  • Drouet L (2002) Atherothrombosis as a systemic disease. Cerebrovasc Dis 13(Suppl 1):1–6

    Article  Google Scholar 

  • Falcone GJ, Malik R, Dichgans M, Rosand J (2014) Current concepts and clinical applications of stroke genetics. Lancet Neurol 13(4):405–418

    Article  Google Scholar 

  • Gretarsdottir S, Thorleifsson G, Manolescu A, Styrkarsdottir U, Helgadottir A, Gschwendtner A, Kostulas K, Kuhlenbäumer G, Bevan S, Jonsdottir T, Bjarnason H, Saemundsdottir J, Palsson S, Arnar DO, Holm H, Thorgeirsson G, Valdimarsson EM, Sveinbjörnsdottir S, Gieger C, Berger K, Wichmann HE, Hillert J, Markus H, Gulcher JR, Ringelstein EB, Kong A, Dichgans M, Gudbjartsson DF, Thorsteinsdottir U, Stefansson K (2008) Risk variants for atrial fibrillation on chromosome 4q25 associate with ischemic stroke. Ann Neurol 64(4):402–409

    Article  Google Scholar 

  • Gschwendtner A, Bevan S, Cole JW, Plourde A, Matarin M, Ross-Adams H et al (2009) Sequence variants on chromosome 9p21.3 confer risk for atherosclerotic stroke. Ann Neurol 65(5):531–539

    Article  CAS  Google Scholar 

  • Hassan A, Markus HS (2000) Genetics and ischaemic stroke. Brain 123(9):1784–1812

    Article  Google Scholar 

  • Hirokawa M, Morita H, Tajima T, Takahashi A, Ashikawa K, Miya F, Shigemizu D, Ozaki K, Sakata Y, Nakatani D, Suna S, Imai Y, Tanaka T, Tsunoda T, Matsuda K, Kadowaki T, Nakamura Y, Nagai R, Komuro I, Kubo M (2015) A genome-wide association study identifies PLCL2 and AP3D1-DOT1L-SF3A2 as new susceptibility loci for myocardial infarction in Japanese. Eur J Hum Genet 23(3):374–380

    Article  CAS  Google Scholar 

  • Jood K, Ladenvall C, Rosengren A, Blomstrand C, Jern C (2005) Family history in ischemic stroke before 70 years of age: the Sahlgrenska Academy Study on Ischemic Stroke. Stroke 36(7):1383–1387

    Article  Google Scholar 

  • Lahoute C, Herbin O, Mallat Z, Tedgui A (2011) Adaptive immunity in atherosclerosis: mechanisms and future therapeutic targets. Nat Rev Cardiol 8(6):348–358

    Article  CAS  Google Scholar 

  • Lemmens R, Buysschaert I, Geelen V, Fernandez-Cadenas I, Montaner J, Schmidt H, Schmidt R, Attia J, Maguire J, Levi C, Jood K, Blomstrand C, Jern C, Wnuk M, Slowik A, Lambrechts D, Thijs V, International Stroke Genetics Consortium (2010) The association of the 4q25 susceptibility variant for atrial fibrillation with stroke is limited to stroke of cardioembolic etiology. Stroke 41(9):1850–1857

    Article  Google Scholar 

  • Libby P (2012) Inflammation in atherosclerosis. Arterioscler Thromb Vasc Biol 32(9):2045–2051

    Article  CAS  Google Scholar 

  • Markus HS (2010a) Genetics studies in ischaemic stroke. Transl Stroke Res 1(4):238–245

    Article  Google Scholar 

  • Markus HS (2010b) Unravelling the genetics of ischaemic stroke. PLoS Med 7(3):e1000225

    Article  Google Scholar 

  • Meschia JF, Bushnell C, Boden-Albala B, Braun LT, Bravata DM, Chaturvedi S, Creager MA, Eckel RH, Elkind MS, Fornage M, Goldstein LB, Greenberg SM, Horvath SE, Iadecola C, Jauch EC, Moore WS, Wilson JA, American Heart Association Stroke Council, Council on Cardiovascular and Stroke Nursing, Council on Clinical Cardiology, Council on Functional Genomics and Translational Biology, Council on Hypertension (2014) Guidelines for the primary prevention of stroke: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 45(12):3754–3832

    Article  Google Scholar 

  • Munshi A, Das S, Kaul S (2015) Genetic determinants in ischaemic stroke subtypes: seven year findings and a review. Gene 555(2):250–259

    Article  CAS  Google Scholar 

  • Otsuki M, Fukami K, Kohno T, Yokota J, Takenawa T (1999) Identification and characterization of a new phospholipase C-like protein, PLC-L(2). Biochem Biophys Res Commun 266(1):97–103

    Article  CAS  Google Scholar 

  • Perry HM, Bender TP, McNamara CA (2012) B cell subsets in atherosclerosis. Front Immunol 3:373

    Article  Google Scholar 

  • Sawcer S, Hellenthal G, Pirinen M, Spencer CC, Patsopoulos NA, Moutsianas L et al (2011) Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature 476(7359):214–219

    Article  CAS  Google Scholar 

  • Takenaka K, Fukami K, Otsuki M, Nakamura Y, Kataoka Y, Wada M, Tsuji K, Nishikawa S, Yoshida N, Takenawa T (2003) Role of phospholipase C-L2, a novel phospholipase C-like protein that lacks lipase activity, in B-cell receptor signaling. Mol Cell Biol 23(20):7329–7338

    Article  CAS  Google Scholar 

  • Tsoi LC, Spain SL, Ellinghaus E, Stuart PE, Capon F, Knight J et al (2015) Enhanced meta-analysis and replication studies identify five new psoriasis susceptibility loci. Nat Commun 6:7001

    Article  CAS  Google Scholar 

  • Ye Z, Huang X, Han Z, Shao B, Cheng J, Wang Z, Zhang Z, Xiao M (2015) Three-year prognosis of first-ever primary pontine hemorrhage in a hospital-based registry. J Clin Neurosci 22(7):1133–1138

    Article  Google Scholar 

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This work was supported by funding from the Zhejiang Provincial Natural Science Foundation – China (LY17H090016, LQ17H090001), National Natural Science Foundation of China (No. 81973620, No. 81774109), Zhejiang Provincial Medical and Health Science Technology Project – China (2018KY122), Major Science and Technology Innovation Project of Wenzhou (2019ZY0012), and Wenzhou Science & Technology Bureau (Y20180135, Y20190131).

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Correspondence to Wujun Geng or Zusen Ye.

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Our study was approved by the ethics committees of the participating hospitals, in compliance with the Declaration of Helsinki. Informed written consent was obtained from the participants (the cases and the controls).

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The authors declare that they have no conflict of interest.

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Huang, X., Zhu, Z., Chen, Y. et al. Two Novel SNPs in the PLCL2 Gene Associated with Large Artery Atherosclerotic Stroke Identified by Fine-Mapping. J Mol Neurosci 70, 496–503 (2020).

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