Association of TOMM40 and SLC22A4 polymorphisms with ischemic stroke

Yamase,Yuichiro; Horibe,Hideki; Ueyama,Chikara; Fujimaki,Tetsuo; Oguri,Mitsutoshi; Kato,Kimihiko; Arai,Masazumi; Watanabe,Sachiro; Yamada,Yoshiji

doi:10.3892/br.2015.457

Association of TOMM40 and SLC22A4 polymorphisms with ischemic stroke

Authors:
- Yuichiro Yamase
- Hideki Horibe
- Chikara Ueyama
- Tetsuo Fujimaki
- Mitsutoshi Oguri
- Kimihiko Kato
- Masazumi Arai
- Sachiro Watanabe
- Yoshiji Yamada
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Affiliations: Department of Cardiovascular Medicine, Gifu Prefectural Tajimi Hospital, Tajimi, Gifu 507‑8522, Japan, Department of Cardiovascular Medicine, Inabe General Hospital, Inabe, Mie 511‑0428, Japan, Department of Cardiology, Kasugai Municipal Hospital, Kasugai, Aichi 486‑8510, Japan, Department of Internal Medicine, Meitoh Hospital, Nagoya, Aichi 465‑0025, Japan, Department of Cardiology, Gifu Prefectural General Medical Center, Gifu 500‑8717, Japan, Department of Human Functional Genomics, Life Science Research Center, Mie University, Tsu, Mie 514‑8507, Japan
Published online on: April 29, 2015 https://doi.org/10.3892/br.2015.457
Pages: 491-498

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Abstract

Recent genome-wide association studies (GWASs) and their meta-analyses have identified various genes and loci underlying the predisposition to ischemic stroke or coronary artery disease in Caucasian populations. Given that ischemic stroke and coronary artery disease may have a shared genetic architecture, certain polymorphisms may confer genetic susceptibility to these two diseases. The aim of the present study was to examine the possible association of ischemic stroke with 29 single‑nucleotide polymorphisms (SNPs) previously identified by the meta‑analyses of GWASs as susceptibility loci for coronary artery disease. The study population comprised 3,187 Japanese individuals, including 894 subjects with ischemic stroke and 2,293 controls. The genotypes for the 29 SNPs of the 28 genes were determined by a method that combines the polymerase chain reaction and sequence‑specific oligonucleotide probes with suspension array technology. Comparisons of the allele frequencies by the χ2 test between subjects with ischemic stroke and controls revealed that rs9319428 (G→A) of the fms‑related tyrosine kinase 1 gene (P=0.0471), rs2075650 (G→A) of the translocase of outer mitochondrial membrane 40 homolog gene (TOMM40, P=0.0102) and rs273909 (T→C) of the solute carrier family 22, member 4 gene (SLC22A4, P=0.0097) were significantly (P<0.05) associated with the prevalence of ischemic stroke. Multivariable logistic regression analysis with adjustment for age, gender, body mass index, smoking status and the prevalence of hypertension, diabetes mellitus and dyslipidemia revealed that rs2075650 of TOMM40 (P=0.0443; recessive model; odds ratio=0.50) and rs273909 of SLC22A4 (P=0.0123; dominant model; odds ratio=0.45) were significantly associated with ischemic stroke with the minor G and C allele, respectively, being protective against this condition. TOMM40 and SLC22A4 may thus be susceptibility loci for ischemic stroke in Japanese individuals.

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1	Tournier-Lasserve E: New players in the genetics of stroke. N Engl J Med. 347:1711–1712. 2002. View Article : Google Scholar : PubMed/NCBI
2	Bak S, Gaist D, Sindrup SH, Skytthe A and Christensen K: Genetic liability in stroke: A long-term follow-up study of Danish twins. Stroke. 33:769–774. 2002. View Article : Google Scholar : PubMed/NCBI
3	Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Blaha MJ, Dai S, Ford ES, Fox CS, Franco S, et al: American Heart Association Statistics Committee and Stroke Statistics Subcommittee: Heart disease and stroke statistics - 2014 update: A report from the American Heart Association. Circulation. 129:e28–e292. 2014. View Article : Google Scholar : PubMed/NCBI
4	Bonita R: Epidemiology of stroke. Lancet. 339:342–344. 1992. View Article : Google Scholar : PubMed/NCBI
5	Warlow C, Sudlow C, Dennis M, Wardlaw J and Sandercock P: Stroke. Lancet. 362:1211–1224. 2003. View Article : Google Scholar : PubMed/NCBI
6	Dichgans M: Genetics of ischaemic stroke. Lancet Neurol. 6:149–161. 2007. View Article : Google Scholar : PubMed/NCBI
7	Roberts R and Stewart AF: The genetics of coronary artery disease. Curr Opin Cardiol. 27:221–227. 2012. View Article : Google Scholar : PubMed/NCBI
8	Banerjee A, Lim CC, Silver LE, Welch SJ, Banning AP and Rothwell PM: Familial history of stroke is associated with acute coronary syndromes in women. Circ Cardiovasc Genet. 4:9–15. 2011. View Article : Google Scholar : PubMed/NCBI
9	Ikram MA, Seshadri S, Bis JC, Fornage M, DeStefano AL, Aulchenko YS, Debette S, Lumley T, Folsom AR, van den Herik EG, et al: Genomewide association studies of stroke. N Engl J Med. 360:1718–1728. 2009. View Article : Google Scholar : PubMed/NCBI
10	Matarín M, Brown WM, Scholz S, Simón-Sánchez J, Fung HC, Hernandez D, Gibbs JR, De Vrieze FW, Crews C, Britton A, et al: A genome-wide genotyping study in patients with ischaemic stroke: Initial analysis and data release. Lancet Neurol. 6:414–420. 2007. View Article : Google Scholar : PubMed/NCBI
11	Yamada Y, Fuku N, Tanaka M, Aoyagi Y, Sawabe M, Metoki N, Yoshida H, Satoh K, Kato K, Watanabe S, et al: Identification of CELSR1 as a susceptibility gene for ischemic stroke in Japanese individuals by a genome-wide association study. Atherosclerosis. 207:144–149. 2009. View Article : Google Scholar : PubMed/NCBI
12	Traylor M, Farrall M, Holliday EG, Sudlow C, Hopewell JC, Cheng YC, Fornage M, Ikram MA, Malik R, Bevan S, et al: Australian Stroke Genetics Collaborative, Wellcome Trust Case Control Consortium 2 (WTCCC2); International Stroke Genetics Consortium: Genetic risk factors for ischaemic stroke and its subtypes (the METASTROKE collaboration): A meta-analysis of genome-wide association studies. Lancet Neurol. 11:951–962. 2012. View Article : Google Scholar : PubMed/NCBI
13	Holliday EG, Maguire JM, Evans TJ, Koblar SA, Jannes J, Sturm JW, Hankey GJ, Baker R, Golledge J, Parsons MW, et al: Australian Stroke Genetics Collaborative; International Stroke Genetics Consortium; Wellcome Trust Case Control Consortium 2: Common variants at 6p21.1 are associated with large artery atherosclerotic stroke. Nat Genet. 44:1147–1151. 2012. View Article : Google Scholar : PubMed/NCBI
14	Schunkert H, König IR, Kathiresan S, Reilly MP, Assimes TL, Holm H, Preuss M, Stewart AF, Barbalic M, Gieger C, et al: Cardiogenics; CARDIoGRAM Consortium: Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease. Nat Genet. 43:333–338. 2011. View Article : Google Scholar : PubMed/NCBI
15	Deloukas P, Kanoni S, Willenborg C, Farrall M, Assimes TL, Thompson JR, Ingelsson E, Saleheen D, Erdmann J, Goldstein BA, et al: CARDIoGRAMplusC4D Consortium; DIAGRAM Consortium; CARDIOGENICS Consortium; MuTHER Consortium; Wellcome Trust Case Control Consortium: Large-scale association analysis identifies new risk loci for coronary artery disease. Nat Genet. 45:25–33. 2013. View Article : Google Scholar : PubMed/NCBI
16	Gschwendtner A, Bevan S, Cole JW, Plourde A, Matarin M, Ross-Adams H, Meitinger T, Wichmann E, Mitchell BD, Furie K, et al: International Stroke Genetics Consortium: Sequence variants on chromosome 9p21.3 confer risk for atherosclerotic stroke. Ann Neurol. 65:531–539. 2009. View Article : Google Scholar : PubMed/NCBI
17	Williams FM, Carter AM, Hysi PG, Surdulescu G, Hodgkiss D, Soranzo N, Traylor M, Bevan S, Dichgans M, Rothwell PM, et al: EuroCLOT Investigators; Wellcome Trust Case Control Consortium 2; MOnica Risk, Genetics, Archiving and Monograph; MetaStroke; International Stroke Genetics Consortium: Ischemic stroke is associated with the ABO locus: The EuroCLOT study. Ann Neurol. 73:16–31. 2013. View Article : Google Scholar : PubMed/NCBI
18	Dichgans M, Malik R, König IR, Rosand J, Clarke R, Gretarsdottir S, Thorleifsson G, Mitchell BD, Assimes TL, Levi C, et al: METASTROKE Consortium; CARDIoGRAM Consortium; C4D Consortium; International Stroke Genetics Consortium: Shared genetic susceptibility to ischemic stroke and coronary artery disease: A genome-wide analysis of common variants. Stroke. 45:24–36. 2014. View Article : Google Scholar : PubMed/NCBI
19	Special report from the National Institute of Neurological Disorders and Stroke. Classification of cerebrovascular diseases III. Stroke. 21:637–676. 1990. View Article : Google Scholar : PubMed/NCBI
20	Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, Yamagata K, Tomino Y, Yokoyama H and Hishida A: Collaborators developing the Japanese equation for estimated GFR: Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis. 53:982–992. 2009. View Article : Google Scholar : PubMed/NCBI
21	Matsuoka R, Abe S, Tokoro F, et al: Association of six genetic variants with myocardial infarction. Int J Mol Med. 35:1451–1459. 2015.PubMed/NCBI
22	Yamada Y, Nishida T, Ichihara S, Sawabe M, Fuku N, Nishigaki Y, Aoyagi Y, Tanaka M, Fujiwara Y, Yoshida H, et al: Association of a polymorphism of BTN2A1 with myocardial infarction in East Asian populations. Atherosclerosis. 215:145–152. 2011. View Article : Google Scholar : PubMed/NCBI
23	Yamada Y, Nishida T, Ichihara S, et al: Identification of chromosome 3q28 and ALPK1 as susceptibility loci for chronic kidney disease in Japanese individuals by a genome-wide association study. J Med Genet. 50:410–418. 2013. View Article : Google Scholar : PubMed/NCBI
24	Itoh Y, Mizuki N, Shimada T, Azuma F, Itakura M, Kashiwase K, Kikkawa E, Kulski JK, Satake M and Inoko H: High-throughput DNA typing of HLA-A, -B, -C and -DRB1 loci by a PCR-SSOP-Luminex method in the Japanese population. Immunogenetics. 57:717–729. 2005. View Article : Google Scholar : PubMed/NCBI
25	Koehler CM, Merchant S and Schatz G: How membrane proteins travel across the mitochondrial intermembrane space. Trends Biochem Sci. 24:428–432. 1999. View Article : Google Scholar : PubMed/NCBI
26	Humphries AD, Streimann IC, Stojanovski D, Johnston AJ, Yano M, Hoogenraad NJ and Ryan MT: Dissection of the mitochondrial import and assembly pathway for human Tom40. J Biol Chem. 280:11535–11543. 2005. View Article : Google Scholar : PubMed/NCBI
27	Deelen J, Beekman M, Uh HW, et al: Genome-wide association study identifies a single major locus contributing to survival into old age; the APOE locus revisited. Aging Cell. 10:686–698. 2011. View Article : Google Scholar : PubMed/NCBI
28	Feulner TM, Laws SM, Friedrich P, Wagenpfeil S, Wurst SH, Riehle C, Kuhn KA, Krawczak M, Schreiber S, Nikolaus S, et al: Examination of the current top candidate genes for AD in a genome-wide association study. Mol Psychiatry. 15:756–766. 2010. View Article : Google Scholar : PubMed/NCBI
29	Aulchenko YS, Ripatti S, Lindqvist I, et al: ENGAGE Consortium: Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts. Nat Genet. 41:47–55. 2009. View Article : Google Scholar : PubMed/NCBI
30	Reiner AP, Barber MJ, Guan Y, Ridker PM, Lange LA, Chasman DI, Walston JD, Cooper GM, Jenny NS, Rieder MJ, et al: Polymorphisms of the HNF1A gene encoding hepatocyte nuclear factor-1 alpha are associated with C-reactive protein. Am J Hum Genet. 82:1193–1201. 2008. View Article : Google Scholar : PubMed/NCBI
31	Ronald J, Rajagopalan R, Ranchalis JE, Marshall JK, Hatsukami TS, Heagerty PJ and Jarvik GP: Analysis of recently identified dyslipidemia alleles reveals two loci that contribute to risk for carotid artery disease. Lipids Health Dis. 8:522009. View Article : Google Scholar : PubMed/NCBI
32	Bekris LM, Lutz F and Yu CE: Functional analysis of APOE locus genetic variation implicates regional enhancers in the regulation of both TOMM40 and APOE. J Hum Genet. 57:18–25. 2012. View Article : Google Scholar : PubMed/NCBI
33	Bennet AM, Di Angelantonio E, Ye Z, Wensley F, Dahlin A, Ahlbom A, Keavney B, Collins R, Wiman B, de Faire U, et al: Association of apolipoprotein E genotypes with lipid levels and coronary risk. JAMA. 298:1300–1311. 2007. View Article : Google Scholar : PubMed/NCBI
34	Bagyinszky E, Youn YC, An SS and Kim S: The genetics of Alzheimer's disease. Clin Interv Aging. 9:535–551. 2014. View Article : Google Scholar : PubMed/NCBI
35	Khan TA, Shah T, Prieto D, Zhang W, Price J, Fowkes GR, Cooper J, Talmud PJ, Humphries SE, Sundstrom J, et al: Apolipoprotein E genotype, cardiovascular biomarkers and risk of stroke: Systematic review and meta-analysis of 14,015 stroke cases and pooled analysis of primary biomarker data from up to 60,883 individuals. Int J Epidemiol. 42:475–492. 2013. View Article : Google Scholar : PubMed/NCBI
36	Bleasby K, Castle JC, Roberts CJ, Cheng C, Bailey WJ, Sina JF, Kulkarni AV, Hafey MJ, Evers R, Johnson JM, et al: Expression profiles of 50 xenobiotic transporter genes in humans and pre-clinical species: A resource for investigations into drug disposition. Xenobiotica. 36:963–988. 2006. View Article : Google Scholar : PubMed/NCBI
37	Mitsuyama H and May JM: Uptake and antioxidant effects of ergothioneine in human erythrocytes. Clin Sci (Lond). 97:407–411. 1999. View Article : Google Scholar : PubMed/NCBI
38	Aruoma OI, Spencer JP and Mahmood N: Protection against oxidative damage and cell death by the natural antioxidant ergothioneine. Food Chem Toxicol. 37:1043–1053. 1999. View Article : Google Scholar : PubMed/NCBI
39	Sakrak O, Kerem M, Bedirli A, Pasaoglu H, Akyurek N, Ofluoglu E and Gültekin FA: Ergothioneine modulates proinflammatory cytokines and heat shock protein 70 in mesenteric ischemia and reperfusion injury. J Surg Res. 144:36–42. 2008. View Article : Google Scholar : PubMed/NCBI
40	Martin KR: The bioactive agent ergothioneine, a key component of dietary mushrooms, inhibits monocyte binding to endothelial cells characteristic of early cardiovascular disease. J Med Food. 13:1340–1346. 2010. View Article : Google Scholar : PubMed/NCBI
41	Akanmu D, Cecchini R, Aruoma OI and Halliwell B: The antioxidant action of ergothioneine. Arch Biochem Biophys. 288:10–16. 1991. View Article : Google Scholar : PubMed/NCBI
42	Cheah IK and Halliwell B: Ergothioneine; antioxidant potential, physiological function and role in disease. Biochim Biophys Acta. 1822:784–793. 2012. View Article : Google Scholar : PubMed/NCBI
43	Peltekova VD, Wintle RF, Rubin LA, Amos CI, Huang Q, Gu X, Newman B, Van Oene M, Cescon D, Greenberg G, et al: Functional variants of OCTN cation transporter genes are associated with Crohn disease. Nat Genet. 36:471–475. 2004. View Article : Google Scholar : PubMed/NCBI
44	Waller S, Tremelling M, Bredin F, Godfrey L, Howson J and Parkes M: Evidence for association of OCTN genes and IBD5 with ulcerative colitis. Gut. 55:809–814. 2006. View Article : Google Scholar : PubMed/NCBI
45	Tokuhiro S, Yamada R, Chang X, Suzuki A, Kochi Y, Sawada T, Suzuki M, Nagasaki M, Ohtsuki M, Ono M, et al: An intronic SNP in a RUNX1 binding site of SLC22A4, encoding an organic cation transporter, is associated with rheumatoid arthritis. Nat Genet. 35:341–348. 2003. View Article : Google Scholar : PubMed/NCBI
46	Santiago JL, Martínez A, de la Calle H, Fernández-Arquero M, Figueredo MA, de la Concha EG and Urcelay E: Evidence for the association of the SLC22A4 and SLC22A5 genes with type 1 diabetes: A case control study. BMC Med Genet. 7:542006. View Article : Google Scholar : PubMed/NCBI