Association Between NINJ2 Gene Polymorphisms and Ischemic Stroke: a Family-based Case-control Study

Overview

Journal J Thromb Thrombolysis

Specialty Cardiology & Vascular Diseases

Date 2014 Mar 26

PMID 24664524

Citations 5

Authors

Yanping Zhu

Kuo Liu

Xun Tang

Jinwei Wang

Zhiping Yu

Yiqun Wu

Dafang Chen

Xueyin Wang

Kai Fang

Na Li

Shaoping Huang

Yonghua Hu

Affiliations

Soon will be listed here.

Abstract

Novel susceptibility genes related to ischemic stroke (IS) are proposed in recent literatures. Population-based replicate studies would cause false positive results due to population stratification. 229 recruit IS patients and their 229 non-IS siblings were used in this study to avoid population stratification. The family-based study was conducted in Beijing from June 2005 to June 2012. Association between SNPs and IS was found in the sibship discordant tests, and the conditional logistic regression was performed to identify effect size and explore gene-environment interactions. Significant allelic association was identified between NINJ2 gene rs11833579 (P = 0.008), protein kinase C η gene rs2230501 (P = 0.039) and IS. The AA genotype of rs11833579 increased 1.51-fold risk (95% CI 1.04-3.46; P = 0.043) of IS, and it conferred susceptibility to IS only in a dominant model (OR 2.69; 95% CI 1.06-6.78; P = 0.036]. Risk of IS was higher (HR 3.58; 95% CI 1.54-8.31; P = 0.003) especially when the carriers of rs11833579 AA genotype were smokers. The present study suggests A allele of rs11833579 may play a role in mediating susceptibility to IS and it may increase the risk of IS together with smoking.

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References

Wu Z, Yao C, Zhao D, Wu G, Wang W, Liu J . Sino-MONICA project: a collaborative study on trends and determinants in cardiovascular diseases in China, Part i: morbidity and mortality monitoring. Circulation. 2001; 103(3):462-8. DOI: 10.1161/01.cir.103.3.462. View

NISHIZUKA Y . Protein kinase C and lipid signaling for sustained cellular responses. FASEB J. 1995; 9(7):484-96. View

Gschwendtner A, Bevan S, Cole J, Plourde A, Matarin M, Ross-Adams H . Sequence variants on chromosome 9p21.3 confer risk for atherosclerotic stroke. Ann Neurol. 2009; 65(5):531-9. PMC: 2702695. DOI: 10.1002/ana.21590. View

Wu L, Shen Y, Liu X, Ma X, Xi B, Mi J . The 1425G/A SNP in PRKCH is associated with ischemic stroke and cerebral hemorrhage in a Chinese population. Stroke. 2009; 40(9):2973-6. DOI: 10.1161/STROKEAHA.109.551747. View

Bazzano L, Gu D, Reynolds K, Wu X, Chen C, Duan X . Alcohol consumption and risk for stroke among Chinese men. Ann Neurol. 2007; 62(6):569-78. DOI: 10.1002/ana.21194. View

Ikram M, Seshadri S, Bis J, Fornage M, DeStefano A, Aulchenko Y . Genomewide association studies of stroke. N Engl J Med. 2009; 360(17):1718-28. PMC: 2768348. DOI: 10.1056/NEJMoa0900094. View

Kubo M, Hata J, Ninomiya T, Matsuda K, Yonemoto K, Nakano T . A nonsynonymous SNP in PRKCH (protein kinase C eta) increases the risk of cerebral infarction. Nat Genet. 2007; 39(2):212-7. DOI: 10.1038/ng1945. View

Tong Y, Zhang Y, Zhang R, Geng Y, Lin L, Wang Z . Association between two key SNPs on chromosome 12p13 and ischemic stroke in Chinese Han population. Pharmacogenet Genomics. 2011; 21(9):572-8. DOI: 10.1097/FPC.0b013e32834911d0. View

Wang Y, Cui L, Ji X, Dong Q, Zeng J, Wang Y . The China National Stroke Registry for patients with acute cerebrovascular events: design, rationale, and baseline patient characteristics. Int J Stroke. 2011; 6(4):355-61. DOI: 10.1111/j.1747-4949.2011.00584.x. View

10.

Helgadottir A, Manolescu A, Thorleifsson G, Gretarsdottir S, Jonsdottir H, Thorsteinsdottir U . The gene encoding 5-lipoxygenase activating protein confers risk of myocardial infarction and stroke. Nat Genet. 2004; 36(3):233-9. DOI: 10.1038/ng1311. View

11.

Ding H, Tu X, Xu Y, Xu C, Wang X, Cui G . No evidence for association of 12p13 SNPs rs11833579 and rs12425791 within NINJ2 gene with ischemic stroke in Chinese Han population. Atherosclerosis. 2011; 216(2):381-2. DOI: 10.1016/j.atherosclerosis.2011.02.005. View

12.

Araki T, Milbrandt J . Ninjurin2, a novel homophilic adhesion molecule, is expressed in mature sensory and enteric neurons and promotes neurite outgrowth. J Neurosci. 2000; 20(1):187-95. PMC: 6774113. View

13.

Bonita R, Mendis S, Truelsen T, Bogousslavsky J, Toole J, Yatsu F . The global stroke initiative. Lancet Neurol. 2004; 3(7):391-3. DOI: 10.1016/S1474-4422(04)00800-2. View

14.

Tang X, Hu Y, Chen D, Zhan S, Zhang Z, Dou H . The Fangshan/Family-based Ischemic Stroke Study In China (FISSIC) protocol. BMC Med Genet. 2007; 8:60. PMC: 1997110. DOI: 10.1186/1471-2350-8-60. View

15.

Gretarsdottir S, Thorleifsson G, Reynisdottir S, Manolescu A, Jonsdottir S, Jonsdottir T . The gene encoding phosphodiesterase 4D confers risk of ischemic stroke. Nat Genet. 2003; 35(2):131-8. DOI: 10.1038/ng1245. View

16.

Rius C, Company C, Piqueras L, Cerda-Nicolas J, Gonzalez C, Servera E . Critical role of fractalkine (CX3CL1) in cigarette smoke-induced mononuclear cell adhesion to the arterial endothelium. Thorax. 2012; 68(2):177-86. DOI: 10.1136/thoraxjnl-2012-202212. View

17.

Matsushita T, Umeno J, Hirakawa Y, Yonemoto K, Ashikawa K, Amitani H . Association study of the polymorphisms on chromosome 12p13 with atherothrombotic stroke in the Japanese population. J Hum Genet. 2010; 55(7):473-6. DOI: 10.1038/jhg.2010.45. View

18.

Pham T, Brown B, Dobson P, Richardson V . Protein kinase C-eta (PKC-eta) is required for the development of inducible nitric oxide synthase (iNOS) positive phenotype in human monocytic cells. Nitric Oxide. 2004; 9(3):123-34. DOI: 10.1016/j.niox.2003.09.006. View

19.

Ambrose J, Barua R . The pathophysiology of cigarette smoking and cardiovascular disease: an update. J Am Coll Cardiol. 2004; 43(10):1731-7. DOI: 10.1016/j.jacc.2003.12.047. View

20.

Iribarren C, Darbinian J, Klatsky A, Friedman G . Cohort study of exposure to environmental tobacco smoke and risk of first ischemic stroke and transient ischemic attack. Neuroepidemiology. 2004; 23(1-2):38-44. DOI: 10.1159/000073973. View