Association of ALOX5AP gene single nucleotide polymorphisms and cerebral infarction in the Han population of northern China

BMC Medical Genetics

Li-ming Zhang³  Zu-yan Zheng²  Bin-bin Zhang¹  Zheng-yi Qu¹  Cui-e Zhang¹  Mei-ling Xu¹  Shuang-yan Zhang¹ 

[1] Department of Neurology, The Fourth Affiliated Clinical College, Harbin Medical University, Yiyuan Street 37, Nangang District, Harbin, China;Department of Neurology, The First Affiliated Hospital Heilongjiang, University of Chinese Medicine, Heping Road 26, Xiangfang District, Harbin, China;Department of Neurology, The First Affiliated Clinical College, Harbin Medical University, Youzheng Street 23, Nangang District, Harbin, China

关键词: SNP;    Han ethnicity;    FLAP;    ALOX5AP;    Cerebral infarction;   

Others  :  1177825
DOI  :  10.1186/1471-2350-13-61

 received in 2011-12-22, accepted in 2012-07-12,  发布年份 2012

【 摘 要 】

Background

To explore the association of ALOX5AP single nucleotide polymorphisms (SNPs) and haplotype with the occurrence of cerebral infarction in the Han population of northern China.

Methods

Blood samples were collected from 236 patients of Han ancestry with a history of cerebral infarction and 219 healthy subjects of Han ancestry with no history of cerebral infarction or cardiovascular disease. Applied Biosystems® TaqMan® SNP Genotyping Assays for SNP genotyping were used to determine the genotypes of 7 ALOX5AP SNP alleles (rs4073259, rs4769874, rs9315050, rs9551963, rs10507391, rs9579646, and rs4147064).

Results

One SNP allele (A) of rs4073259 was significantly associated with development of cerebral infarction (P = 0.049). In comparison to control groups, haplotype rs9315050&rs9551963 AAAC [OR (95% CI) =1.53 (1.02-2.29)], and genotypes rs4147064 CT [OR (95% CI) =1.872 (1.082-3.241)], and rs9551963 AC [OR (95% CI) = 2.015 (1.165-3.484)] increased the risk of cerebral infarction in patients with hypertension. Genotype rs9579646 GG [OR (95% CI) = 2.926 (1.18-7.251)] increased the risk of, while rs4073259 GG [OR (95% CI) = 0.381 (0.157-0.922)] decreased the risk of cerebral infarction in patients with diabetes.

Conclusion

These results suggest the ALOX5AP SNP A allele in rs4073259 and genotype rs9579646 GG, rs9551963 AC, and haplotype rs9315050 & rs9551963 AAAC were associated with an increased risk of ischemic stroke in the Han population, while rs4073259 GG was associated with a decreased risk.

【 授权许可】

   
2012 Zhang et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Helgadottir A, Manolescu A, Thorleifsson G, Gretarsdottir S, Jonsdottir H, Thorsteinsdottir U, Samani NJ, Gudmundsson G, Grant SF, Thorgeirsson G, Sveinbjornsdottir S, Valdimarsson EM, Matthiasson SE, Johannsson H, Gudmundsdottir O, Gurney ME, Sainz J, Thorhallsdottir M, Andresdottir M, Frigge ML, Topol EJ, Kong A, Gudnason V, Hakonarson H, Gulcher JR, Stefansson K: The gene encoding 5-lipoxygenase activating protein confers risk of myocardial infarction and stroke. Nat Genet 2004, 36:233-239.
• [2]Lõhmussaar E, Gschwendtner A, Mueller JC, Org T, Wichmann E, Hamann G, Meitinger T, Dichgans M: ALOX5AP gene and the PDE4D gene in a central European population of stroke patients. Stroke 2005, 36:731-736.
• [3]Helgadottir A, Manolescu A, Helgason A, Thorleifsson G, Thorsteinsdottir U, Gudbjartsson DF, Gretarsdottir S, Magnusson KP, Gudmundsson G, Hicks A, Jonsson T, Grant SF, Sainz J, O'Brien SJ, Sveinbjornsdottir S, Valdimarsson EM, Matthiasson SE, Levey AI, Abramson JL, Reilly MP, Vaccarino V, Wolfe ML, Gudnason V, Quyyumi AA, Topol EJ, Rader DJ, Thorgeirsson G, Gulcher JR, Hakonarson H, Kong A, Stefansson K: A variant of the gene encoding leukotriene A4 hydrolase confers ethnicity-specific risk of myocardial infarction. Nat Genet 2006, 38:68-74.
• [4]Meschia JF, Brott TG, Brown RD Jr: Crook R, Worrall BB, Kissela B, Brown WM, Rich SS, Case LD, Evans EW, Hague S, Singleton A, Hardy J: Phosphodiesterase 4D and 5-lipoxygenase activating protein in ischemic stroke. Ann Neurol 2005, 58:351-361.
• [5]Zhang WL, Yang XM, Shi J, Sun K, Hui RT: Polymorphism of SG13S114T/A in the ALOX5AP gene and the risk for stroke in a large Chinese cohort. Acta Genetica Sinica 2006, 33:678-684.
• [6]Zee RY, Cheng S, Hegener HH, Erlich HA, Ridker PM: Genetic variants of arachidonate 5-lipoxygenase-activating protein, and risk of incident myocardial infarction and ischemic stroke: a nested case–control approach. Stroke 2006, 37:2007-2011.
• [7]Kostulas K, Gretarsdottir S, Kostulas V, Manolescu A, Helgadottir A, Thorleifsson G, Gudmundsson LJ, Thorsteinsdottir U, Gulcher JR, Stefansson K, Hillert J: PDE4D and ALOX5AP genetic variants and risk for ischemic cerebrovascular disease in Sweden. J Neurol Sci 2007, 263:113-117.
• [8]Yamada Y, Kato K, Oguri M, Yoshida T, Yokoi K, Watanabe S, Metoki N, Yoshida H, Satoh K, Ichihara S, Aoyagi Y, Yasunaga A, Park H, Tanaka M, Nozawa Y: Association of genetic variants with atherothrombotic cerebral infarction in Japanese individuals with metabolic syndrome. Int J Mol Med 2008, 21:801-808.
• [9]Kaushal R, Pal P, Alwell K, Haverbusch M, Flaherty M, Moomaw C, Sekar P, Kissela B, Kleindorfer D, Chakraborty R, Broderick J, Deka R, Woo D: Association of ALOX5AP with ischemic stroke: a population-based case–control study. Hum Genet 2007, 121:601-607.
• [10]Helgadottir A, Gretarsdottir S, St Clair D, Manolescu A, Cheung J, Thorleifsson G, Pasdar A, Grant SF, Whalley LJ, Hakonarson H, Thorsteinsdottir U, Kong A, Gulcher J, Stefansson K, MacLeod MJ: Association between the gene encoding 5-lipoxygenase-activating protein and stroke replicated in a Scottish population. Am J Hum Genet 2005, 76:505-509.
• [11]Wang X: The diagnosis of various types of cerebral vascular disease. Chin J Neurol 1996, 12:379.
• [12]Xu ML, Zhang SY, Zhang C, Ma MJ, Zhang LM, Liang QC: Association between the SNPs of ALOX5AP and cerebral infarction in a northern Chinese Han population. Journal of Harbin Medical University 2010, 44(4):326-329.
• [13]Zintzaras E, Rodopoulou P, Sakellaridis N: Variants of the arachidonate 5-lipoxygenase-activating protein (ALOX5AP) gene and risk of stroke: a HuGE gene-disease association review and meta-analysis. Am J Epidemiol 2009, 169:523-532.
• [14]Yandava CN, Kennedy BP, Pillari A, Duncan AM, Drazen JM: Cytogenetic and radiation hybrid mapping of human arachidonate5-lipoxygenase-activating protein (ALOX5AP) to chromosome 13q12. Genomics 1999, 56:131-133.
• [15]Libby P, Ridker PM, Maseri A: Inflammation in atherosclerosis. Circulation 2002, 105:1135-1143.
• [16]Spanbroek R, Grabner R, Lotzer K, Hildner M, Urbach A, Ruhling K, Moos MP, Kaiser B, Cohnert TU, Wahlers T, Zieske A, Plenz G, Robenek H, Salbach P, Kuhn H, Radmark O, Samuelsson B, Habenicht AJ: Expanding expressing of 5-lipoxygenase pathway within the arterial wall during human atherosclerosis. Pro Natl Acad Sci U S A 2003, 100:1238-1243.
• [17]Caiming L, Cheng Z: The genetics research progress of cerebrovascular disease. J Stroke Nervous Dis 2004, 4:185-187. in Chinese
• [18]De Caterina R, Zampolli A: From asthma to atherosclerosis–5-lipoxygenase, leukotrienes, and inflammation. N Engl J Med 2004, 350:4-7.
• [19]Evans JF, Ferguson AD, Mosley RT, Hutchinson JH: What's all the FLAP about?: 5-lipoxygenase-activating protein inhibitors for inflammatory diseases. Trends Pharmacol Sci 2008, 29:72-78.
• [20]Linsel-Nitschke P, Götz A, Medack A, König IR, Bruse P, Lieb W, Mayer B, Stark K, Hengstenberg C, Fischer M, Baessler A, Ziegler A, Schunkert H, Erdmann J: Genetic variation in the arachidonate 5-lipoxygenase-activating protein (ALOX5AP) is associated with myocardial infarction in the German population. Clin Sci (Lond) 2008, 115:309-315.
• [21]Ji R, Jia J, Ma X, Wu J, Zhang Y, Xu L: Genetic variants in the promoter region of the ALOX5AP gene and susceptibility of ischemic stroke. Cerebrovasc Dis 2011, 32:261-268.
• [22]Horvath S, Xu X, Laird NM: The family based association test method: strategies for studying general genotype–phenotype associations. Eur J Hum Genet 2001, 9:301-306.