Cyclooxygenase 2 Genetic Polymorphism May Increase the Risk of Developing Leukoaraiosis in Chinese

Xu, Shan; Chen, Guozhong; Cheng, Gan-ping; Tao, Hong-miao

doi:10.1007/s12031-013-0066-9

Cited by 8 publications

(9 citation statements)

References 29 publications

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“…The finding is in agreement with a recent case-control Chinese study showing an association between WMH and two functional COX-2 gene polymorphisms (rs20417 and rs689466)(23). White matter disease is a marker of small vessel disease and increases with aging and cumulative burden of cerebrovascular risk factors(12, 18).…”

Section: Discussionsupporting

confidence: 93%

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COX-2 rs20417 Polymorphism Is Associated with Stroke and White Matter Disease

Oliveira‐Filho

Ornellas

Zhang

et al. 2015

Journal of Stroke and Cerebrovascular Diseases

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Goals To investigate the effect of COX-2 polymorphism and its product, prostaglandin-E2 (PGE2), on stroke risk in an endemic area for Chagas disease. In a separate cohort, to investigate the effect of COX-2 polymorphisms on the total burden of cerebral white matter disease. Methods Cases were outpatients with ischemic stroke; controls were stroke-free subjects from two outpatient clinics (heart failure and caregivers of a movement disorders clinic). We extracted DNA from total blood to investigate the rs20417 COX-2 polymorphism. Serologic tests (ELISA) were performed to confirm T. cruzi infection and to quantify PGE2 levels. In the Boston cohort, white matter hyperintensity volume (WMHv) was quantified on the admission brain MRIs of subjects with ischemic stroke, who also donated DNA for the COX-2 gene region analysis. Findings We studied 44 patients with stroke and 96 controls (46 with heart failure and 50 caregivers) in the Brazilian cohort; and 788 stroke patients (302 cardioembolic, 486 non-cardioembolic) in the Boston cohort. In the Brazilian cohort, rs20417 polymorphism was associated with both stroke (p=5x10−6) and decreased PGE2 levels (p=4x10−5); similarly, Chagas was associated with stroke (p=4x10−3) and decreased PGE2 levels (p=7x10−3). In the Boston cohort, rs20417 polymorphism was associated with increased WMHv among non-cardioembolic (p=0.037), but not among cardioembolic stroke patients. Conclusions Variation in COX-2 gene is associated with both symptomatic and silent brain cerebrovascular disease. This candidate gene region should be tested in population-based samples.

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Section: Discussionsupporting

confidence: 93%

“…While adequately powered cohorts have suggested an association(19–23), the most recent meta-analysis did not confirm prior findings(2). One potential explanation is that the association is highly dependent on the interaction with environmental factors affecting expression of the gene.…”

Section: Discussionmentioning

confidence: 75%

COX-2 rs20417 Polymorphism Is Associated with Stroke and White Matter Disease

Oliveira‐Filho

Ornellas

Zhang

et al. 2015

Journal of Stroke and Cerebrovascular Diseases

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“…In addition, 15 SNPs were included in the second group ( Table 1 ). Since they resulted in the missense changes, those SNPs were chosen from 28 SNPs which were reported to be related with the risk of WMHs or WMLs in previous candidate gene association studies amongst European or American individuals and listed in Supplemental Table 1 (Schmidt et al, 2000; Henskens et al, 2005; van Rijn et al, 2006; Fornage et al, 2007; Hogh et al, 2007; van Rijn et al, 2007; Taylor et al, 2008; Godin et al, 2009; Paternoster et al, 2009; Fernandez-Cadenas et al, 2011; Shan et al, 2013; Lin et al, 2015). Eleven of 28 SNPs were excluded from the present study since they were located in the non-coding regions of genes and considered to be non-functional SNPs.…”

Section: Methodsmentioning

confidence: 99%

The Associations of PMF1, ICAM1, AGT, TRIM65, FBF1, and ACOX1 Variants With Leukoaraiosis in Chinese Population

Huang

Cai

et al. 2019

Front. Genet.

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Background: Leukoaraiosis (LA) is shown as white matter hyperintensities on T2-weighted magnetic resonance imaging brain scans. Together with candidate gene association studies (CGAS), multiple genome-wide association studies (GWAS) have reported large numbers of single nucleotide polymorphisms (SNPs) to be associated with LA in European populations. To date, no replication studies have been reported in independent Chinese samples. Methods: Here, we performed a candidate gene association study comprising 220 Chinese subjects with LA and 50 controls. Thirty-nine polymorphisms on 32 risk genes were selected from previous studies, and they were genotyped through matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Genetic association analysis was firstly performed in all subjects with LA. Then, the same analysis was conducted in the six random sampling cohorts of 50 LA patients, respectively. Data analyses on the associations of SNPs with LA risk were evaluated through Pearson’s χ 2 and multivariate logistic regression tests. Results: We found that eight polymorphisms in six genes ( PMF1 , ICAM1 , TRIM65 , AGT , FBF1 , and ACOX1 ) were significantly associated with LA in the genetic association tests. Except for those eight gene variants, 24 other polymorphisms were not found to be significantly associated with LA in general genetic model, dominant model, recessive model, or multiplicative model. Among those eight polymorphisms, rs2984613 in PMF1 showed significant association with LA in the cohort of 220 LA subjects, and such significant association remained in both general genetic model (OR: 0.262, 95% CI: 0.091–0.752, p adj = 0.030) and recessive model (OR: 0.323, 95% CI: 0.119–0.881, p adj = 0.038) when controlling for clinical variables. Seven other significant variants (rs5498 in ICAM1 , rs699 in AGT , rs2305913 in FBF1 , rs1135640 in ACOX1 , and rs3760128, rs7214628, and rs7222757 in TRIM65 ) were identified in those six random sampling tests that were conducted in the adjusted cohorts of 50 LA patients. In addition, except for rs699 which showed detrimental effect and represented a risk variant for LA, seven other polymorphisms seemed to exert protective effects on LA and to reduce the risk of LA. It is necessary to confirm these associations in an independent cohort. Conclusions: This first replication study on multiple genes in an independent Chinese population did not replicate any risk polymorphisms for LA other than rs 699 in AGT but revealed the significantly negative associations of ...

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“…It has been shown that the COX-2-765G>C polymorphism is a protective factor against ischemic stroke in Italians [34], but the association between COX-2-765G>C and ischemic stroke and leukoaraiosis could not be replicated in Chinese [27,38] and Koreans [39]. As for COX-2-8473T>C, Maguire et al [40] demonstrated a significant effect of the COX-2-8473T>C polymorphisms on ischemic stroke functional outcome in Australians, while no association between the COX-2-8473T>C polymorphisms and intracerebral hemorrhage was observed in Koreans [41].…”

Section: Plos Onementioning

confidence: 99%

Association of the cyclooxygenase-2 1759A allele with migraine in Chinese Han individuals

et al. 2020

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Cyclooxygenase-2 (COX-2) is known to be involved in the pathogenesis of migraine, and some polymorphisms are known to affect the expression of COX-2. This retrospective casecontrol study aimed to explore the associations between the-765 G>C (rs20417),-1759 G>A (rs3218625), and-8473 C>T (rs5275) COX-2 polymorphisms and migraine in Chinese Han individuals. One hundred and ten unrelated Han Chinese patients with migraine and 108 healthy controls were recruited between 03/2014 and 08/2016 at the First Affiliated Hospital of Nanjing Medical University and the First People's Hospital of Lianyungang City. The genotypes of all polymorphisms in controls followed the Hardy-Weinberg equilibrium (P = 0.215, P = 0.884, and P = 0.689). There were differences in the genotype and allele distributions of the COX-2-1759G>A (Gly587Arg) polymorphism between the migraine and control groups (P = 0.038 and P = 0.040, respectively). Compared with the COX-2-1759AG genotype, GG genotype carriers had an increased risk of migraine (odds ratio (OR) = 8.720, 95% confidence interval (CI): 1.072-70.960, P = 0.038). The frequency of the COX-2-1759A allele in patients with migraine was significantly lower than the controls (OR = 0.119, 95%CI: 0.015-0.957, P = 0.040). Adjusted age and sex, a statistical difference was found in the dominant model of COX-2-1759 G>A (OR = 0.118, 95% CI 0.014 to 0.962, P = 0.046). No significant difference was detected regarding the-765G>C and-8473T>C polymorphisms between the two groups. The COX-2 1759A allele might be involved in the development of migraine in Chinese Han individuals, but this will have to be confirmed in large-scale studies.

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Cyclooxygenase 2 Genetic Polymorphism May Increase the Risk of Developing Leukoaraiosis in Chinese

Cited by 8 publications

References 29 publications

COX-2 rs20417 Polymorphism Is Associated with Stroke and White Matter Disease

COX-2 rs20417 Polymorphism Is Associated with Stroke and White Matter Disease

The Associations of PMF1, ICAM1, AGT, TRIM65, FBF1, and ACOX1 Variants With Leukoaraiosis in Chinese Population

Association of the cyclooxygenase-2 1759A allele with migraine in Chinese Han individuals

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