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

Abstract

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.

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

“…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) .…”

“…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.…”

“…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.…”

“…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.…”

“…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.…”