A Haplotype of the CYP4F2 Gene is Associated With Cerebral Infarction in Japanese Men

Fu, Zhen-Yan; Nakayama, Tomohiro; Sato, Naoyuki; Izumi, Yasukatsu; Kasamaki, Yuji; Shindo, Atsushi; Ohta, Masakatsu; Soma, Masayoshi; Aoi, Noriko; Sato, Mitsugu; Matsumoto, Koichí; Ozawa, Yukio; Ma, Yun

doi:10.1038/ajh.2008.276

Cited by 33 publications

(38 citation statements)

References 28 publications

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“…Apart from the rs9333025 variant, there were no significant differences in association with IS identified for other variants using a singlelocus analytical approach. These results were consistent with those of some previous studies 29,34,35) and in contrast to some others 20,22,[25][26][27][28][36][37][38] . For instance, Gschwendtner et al have reported that genetic variations in the EPHX2 gene are associated with IS risk, an association that has been described as predominantly mediated by large-vessel disease 36) .…”

Section: Logistic Regression Analysissupporting

confidence: 83%

“…In addition, Ward et al have reported that a single polymorphism in the CYP4F2 gene is associated with increased 20-HETE 38) . Some studies also have reported that CYP4F2 polymorphisms are associated with IS risk [25][26][27][28] . There could be numerous potential explanations for the differences in the findings of the present study.…”

Section: Logistic Regression Analysismentioning

confidence: 99%

“…These findings indicate that interactions of rs17110453, rs751141, and rs9333025 could potentially provide these individuals with lower circulating EET levels and higher 20-HETE levels than those without this particular three-gene-variant interaction, thereby increasing the risk of IS. According to previous studies [20][21][22][25][26][27][28][29] and the results of this study, rs17110453AA, rs751141AA, and rs9333025AA are low-risk genotypes. Thus, the associations between IS and different combinations of genotypes were compared with rs17110453AA, rs751141AA, and rs9333025AA.…”

Section: Logistic Regression Analysismentioning

confidence: 99%

“…20-HETE plays an important role in the autoregulation of cerebral blood flow 23) , and blockade of 20-HETE synthesis reduced the infarct size in a middle cerebral artery occlusion model of IS 24) . The CYP4A11 and CYP4F2 genes encode CYP -hydroxylase, and the V433M polymorphisms of CYP4F2 [25][26][27][28] as well as the CYP4A11 C-296T mutation 29) have been independently associated with an elevated risk of IS.…”

Section: Participantsmentioning

confidence: 99%

“…The single-nucleotide polymorphisms (SNPs) of the CYP2J2, CYP2C8, CYP2C9 2, CYP2C9 3, CYP3A5, and EPHX2 genes in the CYP epoxygenase pathway as well as the CYP4A11 and CYP4F2 genes encoding CYP -hydroxylase were selected from the NCBI database (http://www.ncbi.nlm.nih.gov/SNP) according to the following criteria: (1) the SNPs had been examined in previous studies and have demonstrated significant associations between the SNPs and stroke [20][21][22][25][26][27][28][29] ; (2) tic regression analyses were performed to adjust some risk factors in order to assess the independent contribution of gene -gene interactions on stroke risk. Odds ratios (ORs) with 95% confidence intervals (CIs) were obtained.…”

Section: Genotypingmentioning

confidence: 99%

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Interaction among CYP2C8, EPHX2, and CYP4A11 Gene Variants Significantly Increases the Risk for Ischemic Stroke in Chinese Populations

Liao

et al. 2015

JAT

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Aim: Ischemic stroke (IS) is a multifactorial disease caused by environmental risk factors and genetic susceptibility. However, few studies have assessed whether gene -gene interactions among cytochrome P450 (CYP) pathway genes influence the risk of IS. The aim of the present study was to investigate the association of 10 variants of eight CYP pathway genes with IS and to determine whether these gene -gene interactions increase the risk of IS. Methods: Ten variants of eight CYP pathway genes were examined using mass spectrometry methods in 396 patients with IS and 378 controls. Gene -gene interactions were analyzed using generalized multifactor dimensionality reduction (GMDR) methods. Results: Apart fro m variant rs9333025, there were no significant differences in the genotype distributions of the other nine variants between the two groups using the single -locus analytical approach. However, the GMDR analysis showed a significant gene -gene interaction among rs17110453, rs751141, and rs9333025, which scored 10 for cross-validation consistency and nine for the sign test (p 0.011). Individual patients with the combination of 17110453CC, rs751141GG, and rs9333025GG had a significantly higher risk for IS than those with the combination of 17110453AA, rs751141AA, and rs9333025AA [odds ratio (OR) 2.86, 95% confidence interval (CI): 1.24 -7.26, p 0.004]. Logistic regression analysis showed that certain gene -gene interactions among rs17110453, rs751141, and rs9333025 predict a higher risk for IS (OR 2.36, 95% CI: 1.228 -5.297, p 0.005). Conclusion:The three-loci interaction may confer a higher risk for IS. The combinatorial analysis used in this study may be helpful to elucidate complex genetic risk factors for IS.

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Section: Logistic Regression Analysissupporting

confidence: 83%

Section: Logistic Regression Analysismentioning

confidence: 99%

Section: Logistic Regression Analysismentioning

confidence: 99%

Section: Participantsmentioning

confidence: 99%

Section: Genotypingmentioning

confidence: 99%

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Interaction among CYP2C8, EPHX2, and CYP4A11 Gene Variants Significantly Increases the Risk for Ischemic Stroke in Chinese Populations

Liao

et al. 2015

JAT

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Eicosanoids and Their Drugs in Cardiovascular Diseases: Focus on Atherosclerosis and Stroke

Capra

Bäck

Barbieri

et al. 2012

Medicinal Research Reviews

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Eicosanoids are biologically active lipids in both physiologic and pathophysiologic situations. These mediators rapidly generate at sites of inflammation and act through specific receptors that following the generation of a signal transduction cascade, lead to coordinated cellular responses to specific stimuli. Prostanoids, that is, prostaglandins and thromboxane A(2), are active products of the cyclooxygenase pathway, while leukotrienes and lipoxins derive from the lipoxygenase pathway. In addition, a complex family of prostaglandin isomers called isoprostanes is derived as free-radical products of oxidative metabolism. While there is a wide consensus on the importance of the balance between proaggregating (thromboxane A(2)) and antiaggregating (prostacyclin) cyclooxygenase products in cardiovascular homeostasis, an increasing body of evidence suggests a key role also for other eicosanoids generated by lipoxygenases, epoxygenases, and nonenzymatic pathways in cardiovascular diseases. This intricate network of lipid mediators is unique considering that from a single precursor, arachidonic acid, may derive an array of bioproducts that interact within each other synergizing or, more often, behaving as functional antagonists.

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Association of 1347 G/A cytochrome P450 4F2 (CYP4F2) gene variant with hypertension and stroke

et al. 2011

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Genetic variants of cytochrome P450 4F2 (CYP4F2) gene have been suggested to be risk factors for hypertension, cardiovascular diseases and stroke. In the present case-control study we investigated the association of 1347 G/A polymorphism (rs2108622) in the 11th exon region of CYP4F2 gene with hypertension, ischemic stroke and stroke subtypes classified according to TOAST (Trial of Org 10172 in Acute Stroke Treatment) classification. Five hundred and seven stroke patients (hypertensives: normotensives = 279:228) and four hundred and eighty seven, age and sex matched controls (males: females = 356:131) (hypertensives: normotensives = 148:339) were involved in the study. The genotypes were determined by PCR-RFLP technique. Genotypes were confirmed by subjecting the PCR products to sequencing. Significant difference was observed in the genotypic distribution and allelic frequency between the stroke patients and healthy controls. AA genotype and A allele associated significantly with stroke and hypertension [P = 0.009; OR = 1.59 (95% CI = 1.119-2.283) and P = 0.010; OR = 1.26 (95% CI = 1.056-1.502); P = 0.01; OR = 1.58 (95% CI = 1.11-2.272) and P = 0.010; OR = 1.25(95% CI = 1.054-1.504) respectively]. A stepwise logistic regression analysis confirmed these findings. To establish that this polymorphism is associated with stroke independent of hypertension; we compared stroke patients without hypertension with normotensive controls. Significant difference was observed in genotypic distribution and allelic frequency between the two groups (P = 0.001 and 0.002 respectively). Evaluating the association of this polymorphism with stroke subtypes we found significant associations with cardioembolic stroke (P < 0.001). In conclusion our study suggests that 1347A allele of CYP4F2 gene is an important risk factor for hypertension and ischemic stroke.

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A Haplotype of the CYP4F2 Gene is Associated With Cerebral Infarction in Japanese Men

Abstract: The results of this study indicate that, in Japanese men, CI is associated with the G allele of rs2108622 and, in addition, that the T-C-G haplotype appears to be a useful genetic marker for CI.

Cited by 33 publications

References 28 publications

Interaction among <i>CYP2C8</i>, <i>EPHX2</i>, and <i>CYP4A11</i> Gene Variants Significantly Increases the Risk for Ischemic Stroke in Chinese Populations

Interaction among <i>CYP2C8</i>, <i>EPHX2</i>, and <i>CYP4A11</i> Gene Variants Significantly Increases the Risk for Ischemic Stroke in Chinese Populations

Eicosanoids and Their Drugs in Cardiovascular Diseases: Focus on Atherosclerosis and Stroke

Association of 1347 G/A cytochrome P450 4F2 (CYP4F2) gene variant with hypertension and stroke

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