Genetic Polymorphisms of Hypoxia-Inducible Factor-1 Alpha and Cardiovascular Disease in Hemodialysis Patients

Abstract

BACKGROUND: Hemodialysis patients are prone to ischemic events potentially aggravated by hypoxia. The key player in adaptation to hypoxia is hypoxia-inducible factor-1 alpha (HIF-1alpha). Therefore, we investigated the association of HIF-1alpha polymorphisms with ischemia/hypoxia-related events in hemodialysis patients. METHODS: Patients on maintenance hemodialysis were enrolled from 4 training hospitals in Korea. Seven single nucleotide polymorphisms (SNP) of HIF-1alpha were genotyped. The association of these SNP with hypoxia-related clinical outcomes (ischemic diseases and anemia) and cancer was analyzed. RESULTS: A total of 376 patients participated in the study. No significant difference in genotype distribution was found between subjects with and without the hypoxia-related events. Three sets of linkage disequilibrium blocks were made for haplotype analyses (rs2783778 and rs7148720 in 5' upstream region; rs7143164 and rs10873142; rs2301113, rs11549465 and rs2057482). Of these, the CT haplotype in the first set was associated with both acute myocardial infarction and frequent intradialytic hypotension (acute myocardial infarction: adjusted odds ratio = 0.15, 95% CI: 0.03-0.69; frequent intradialytic hypotension: adjusted odds ratio = 0.29, 95% CI: 0.12-0.72). CONCLUSION: Genetic polymorphisms of HIF-1alpha were associated with acute myocardial infarction and intradialytic hypotension in hemodialysis patients.