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Variation in the human soluble epoxide hydrolase gene and risk of restenosis after percutaneous coronary intervention.

ABSTRACT: BACKGROUND: Restenosis represents the major limiting factor for the long-term efficacy of percutaneous coronary intervention (PCI). Several genetic factors involved in the regulation of the vascular system have been described to play a role in the pathogenesis of restenosis. We investigated whether the EPHX2 K55R polymorphism, previously linked to significantly higher risk for coronary heart disease (CHD), was associated with the occurrence of restenosis after PCI. The association with incident CHD should have been confirmed and a potential correlation of the EPHX2 K55R variant to an increased risk of hypertension was analysed. METHODS: An overall cohort of 706 patients was studied: This cohort comprised of 435 CHD patients who had undergone successful PCI. Follow-up coronary angiography in all patients was performed 6 months after intervention. Another 271 patients in whom CHD had been excluded by coronary angiography served as controls. From each patient EDTA-blood was drawn at the baseline ward round. Genomic DNA was extracted from these samples and genotyping was performed by real-time PCR and subsequent melting curve analysis. RESULTS: In CHD patients 6 month follow-up coronary angiography revealed a restenosis rate of 29.4%, classified as late lumen loss as well as lumen re-narrowing >or= 50%.Statistical analysis showed an equal genotype distribution in restenosis patients and non-restenosis patients (A/A 82.0% and A/G + G/G 18.0% versus A/A 82.1% and A/G + G/G 17.9%). Moreover, neither a significant difference in the genotype distribution of CHD patients and controls nor an association with increased risk of hypertension was found. CONCLUSION: The results of the present study indicate that the EPHX2 K55R polymorphism is not associated with restenosis after PCI, with incidence of CHD, or with an increased risk of hypertension and therefore, can not serve as a predictor for risk of CHD or restenosis after PCI.

SUBMITTER: Kullmann S

PROVIDER: S-EPMC2767343 | biostudies-literature | 2009

REPOSITORIES: biostudies-literature

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Variation in the human soluble epoxide hydrolase gene and risk of restenosis after percutaneous coronary intervention.

Kullmann Silke S Binner Priska P Rackebrandt Kirsten K Huge Andreas A Haltern Georg G Lankisch Mark M Füth Reiner R von Hodenberg Eberhard E Bestehorn Hans-Peter HP Scheffold Thomas T

BMC cardiovascular disorders 20091008

<h4>Background</h4>Restenosis represents the major limiting factor for the long-term efficacy of percutaneous coronary intervention (PCI). Several genetic factors involved in the regulation of the vascular system have been described to play a role in the pathogenesis of restenosis. We investigated whether the EPHX2 K55R polymorphism, previously linked to significantly higher risk for coronary heart disease (CHD), was associated with the occurrence of restenosis after PCI. The association with in ...[more]

PMID: 19814804

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Project description:Background Single nucleotide polymorphisms (SNPs) in the EPHX2 gene have been implicated in susceptibility to cardiovascular diseases, including coronary heart disease (CHD). EPHX2 encodes for soluble epoxide hydrolase, an important enzyme involved in the metabolic breakdown of arachidonic acid-derived vasoactive and anti-inflammatory eicosanoids referred to as epoxyeicosatrienoic acids to their corresponding diols. Our pilot study aimed to investigate whether common SNPs such as rs751141, rs4149253, and rs1042064 of the EPHX2 gene are associated with susceptibility to CHD in Russian population. Methods A total of 1,183 unrelated Russian subjects comprising 602 patients with angiographically diagnosed CHD and 581 age- and sex-matched healthy subjects were recruited and their DNA samples were genotyped for the selected SNPs using a high-throughput Mass-ARRAY genotyping platform. Results No significant associations were found between the investigated SNPs and CHD risk (P>0.05). A polymorphism rs751141 (amino acid substitution, R287Q) displayed a trend towards association with CHD (odds ratio adjusted by sex and age was 3.02, 95% CI: 0.97–9.43, P correction =0.16). SNP-smoking interaction analyses did not identify synergic effects of the studied SNPs and cigarette smoking on the disease risk (P>0.05). A linkage disequilibrium was found between SNPs rs751141 and rs4149253 (D’ =0.995), rs751141 and rs1042064 (D’ =0.967), rs4149253 and rs1042064 (D’ =0.965). Four common haplotypes G-G-T (73%), A-G-C (10%), G-G-C (9%) and G-A-C (7%) have been identified, however, none of them showed a significant association with the risk of CHD in the studied population (P>0.05). Conclusions The investigated polymorphisms do not contribute to CHD susceptibility in our population. Nevertheless, because of a limited number of SNPs was investigated in this study, definitive conclusions yet to be made in further studies on the contribution of the EPHX2 gene to the development of CHD in Russians.

Dataset Information

Variation in the human soluble epoxide hydrolase gene and risk of restenosis after percutaneous coronary intervention.

Publications

Variation in the human soluble epoxide hydrolase gene and risk of restenosis after percutaneous coronary intervention.

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