title: Cyclooxygenase-2 genetic polymorphism and stroke subtypes in Chinese.
abstract: BACKGROUND
  Cyclooxygenase-2 (COX-2) catalyzes the formation of prostaglandins that contribute to the inflammation in atherosclerosis. The aim of the present study was to investigate the relationship between two polymorphisms (-1195G>A and -765G>C) in the COX-2 gene and subtypes of ischemic stroke in a Chinese population.
  
  
  METHODS
  Genomic DNA of 224 patients with large artery atherosclerosis (LAA), 329 patients with small vessel occlusion (SVO), and 450 controls were genotyped for the COX-2 1195G>A (rs689466) and -765G>C (rs20417) polymorphisms using polymerase chain reaction-restriction fragment length polymorphism. Chi-square test and logistic regression analysis were performed for association analysis.
  
  
  RESULTS
  The frequencies of variant allele with -1195G>A and -765G>C polymorphisms were 0.46 and 0.22, respectively. The -1195GA genotype and 1195A allele carriers were identified independently to be related with ischemic stroke (adjusted OR = 1.51, 95 % CI: 1.09-2.10, P = 0.02; OR = 1.45, 95 % CI: 1.06-1.97, P = 0.02) and SVO (adjusted OR = 1.57, 95 % CI: 1.07-2.30, P = 0.02; OR = 1.50, 95 % CI: 1.05-2.16, P = 0.03). In contrast, the 1195G>A polymorphism was not associated with LAA. No relationship between the -765G>C polymorphism and risk of either ischemic stroke was observed. The linkage disequilibrium analysis showed that -1195G>A and -765G>C SNPs are moderate linkage disequilibrium in this study population (D' = 0.72, r (2) = 0.16). Compared with G-1195-G-765 haplotype, the haplotype of A-1195-G-765 showed significant increased risk of ischemic stroke (OR = 1.27, 95 % CI: 1.05-1.54, P = 0.02) and SVO (OR = 1.27, 95 % CI: 1.02-1.58, P = 0.03) but not LAA.
  
  
  CONCLUSIONS
  In conclusion, we found that -1195G>A polymorphism and A-1195-G-765 haplotype of COX-2 were associated with susceptibility to ischemic stroke in a Chinese population. The effects were confined to SVO among the stroke subtypes rather than to LAA.
authors.affiliation: Tongde Hospital of Zhejiang Province, Hangzhou, 311122, Zhejiang Province, People's Republic of China.
authors.forename: Guo-zhong
authors.initials: GZ
authors.lastname: Chen
authors.forename: Xiao-yun
authors.initials: XY
authors.lastname: Shan
authors.forename: Gan-ping
authors.initials: GP
authors.lastname: Cheng
authors.forename: Hong-miao
authors.initials: HM
authors.lastname: Tao
mesh_terms: D000328:Adult; D000368:Aged; D002545:Brain Ischemia / Q000235:genetics*; D016022:Case-Control Studies; D002681:China; D051546:Cyclooxygenase 2 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D020521:Stroke / Q000235:genetics*
chemical_list: D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human
references.citation: Arterioscler Thromb Vasc Biol. 2002 Oct 1;22(10):1631-6
references.pmid: 12377741
references.citation: Annu Rev Pharmacol Toxicol. 1998;38:97-120
references.pmid: 9597150
references.citation: Neurosci Res. 2009 Jul;64(3):311-6
references.pmid: 19447301
references.citation: Lancet Neurol. 2004 Jul;3(7):391-3
references.pmid: 15207791
references.citation: Atherosclerosis. 2008 Feb;196(2):926-30
references.pmid: 17350020
references.citation: Stroke. 2003 Jun;34(6):1364-9
references.pmid: 12714707
references.citation: World J Gastroenterol. 2011 Sep 28;17(36):4113-7
references.pmid: 22039326
references.citation: Can J Neurol Sci. 2012 Sep;39(5):626-31
references.pmid: 22931704
references.citation: Atherosclerosis. 2009 Jun;204(2):e58-63
references.pmid: 19046748
references.citation: PLoS One. 2010 Nov 24;5(11):e15011
references.pmid: 21124790
references.citation: Nature. 2002 Dec 19-26;420(6917):868-74
references.pmid: 12490960
references.citation: Stroke. 2005 Mar;36(3):533-9
references.pmid: 15692115
references.citation: Blood Coagul Fibrinolysis. 2006 Mar;17(2):93-6
references.pmid: 16479190
references.citation: Cytokine. 2011 Dec;56(3):550-9
references.pmid: 22019000
references.citation: Stroke. 1993 Jan;24(1):35-41
references.pmid: 7678184
references.citation: Atherosclerosis. 2009 Apr;203(2):459-65
references.pmid: 18768181
references.citation: Clin Chim Acta. 2006 Jun;368(1-2):138-43
references.pmid: 16458279
references.citation: Gastroenterology. 2005 Aug;129(2):565-76
references.pmid: 16083713
references.citation: Genomics. 1994 Oct;23(3):718-9
references.pmid: 7851909
references.citation: JAMA. 2004 May 12;291(18):2221-8
references.pmid: 15138244
references.citation: Brain. 2000 Sep;123 ( Pt 9):1784-812
references.pmid: 10960044
references.citation: Stroke. 2006 Nov;37(11):2843-5
references.pmid: 16990569
references.citation: Clin Pharmacol Ther. 2008 Jan;83(1):52-60
references.pmid: 17495879
references.citation: Stroke. 2005 Sep;36(9):2027-31
references.pmid: 16051898
references.citation: Circulation. 2001 Aug 21;104(8):921-7
references.pmid: 11514380
references.citation: Stroke. 2007 Oct;38(10):2663-9
references.pmid: 17702963
references.citation: Front Biosci (Schol Ed). 2012 Jan 01;4:620-38
references.pmid: 22202081
references.citation: FASEB J. 2004 May;18(7):790-804
references.pmid: 15117884
references.citation: Arterioscler Thromb Vasc Biol. 2004 Jul;24(7):1259-65
references.pmid: 15155382