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-1α). Therefore, we investigated the association of HIF-1α 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-1α 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-1α were associated with acute myocardial infarction and intradialytic hypotension in hemodialysis patients.

Genetic variations in hypoxia response genes influence hypertrophic cardiomyopathy phenotype

“…Single-nucleotide polymorphisms (SNP) frequencies were similar in the two cohorts and comparable with those reported in the general population ( Table 1) (16)(17)(18). The two cohorts were comparable except for a higher frequency of blacks in cohort 1 vs. 2 (21% vs. 0%).…”

“…Genotyping was performed for SNPs chosen based on previous association studies, functional effects, allele frequency, and prevalence (16)(17)(18): VEGFA 2578A/C, VEGFA 1154A/G, both SNPs in the VEGF promoter, VEGFA 634C/G in the 5′ untranslated region, HIF1A 145C/T, HIF1A 1326C/T, and HIF1A 1744C/T in the 3′ untranslated region ( Table 6). Functioning alleles (major alleles) in HIF1A and loss-of-function alleles (minor alleles) in VEGFA were considered risk alleles.…”

“…Functioning alleles (major alleles) in HIF1A and loss-of-function alleles (minor alleles) in VEGFA were considered risk alleles. These alleles have shown previous associations with coronary artery disease and chronic heart failure (16,17,(38)(39)(40)(41). SNP assays were performed using Applied Biosystems Taqman SNP genotyping technology (Assays-by-Design, Burlington, Canada).…”

Polymorphisms of HIF1A gene are associated with prognosis of early stage non-small-cell lung cancer patients after surgery

“…Finally, we found only one functional SNP locus (rs2057482), which located in the 3′-UTR. Another SNP locus, rs2301113, was selected as previous studies reported [26, 27]. Genotyping was performed using Sequenom iPLEX genotyping system (Sequenom Inc, CA).…”

Common Polymorphisms in Angiogenesis

“…In contrast, in hemodialysis patients, polymorphisms are associated with acute myocardial infarction and hypotension (Zheng et al 2009). It is also associated with susceptibility to systemic sclerosis, a disease characterized by vascular inflammation and angiopathy (Wipff et al 2009).…”