Investigation of hypoxia-inducible factor-1alpha (HIF-1α) gene polymorphisms in individuals with high levels of hemoglobin

Objective: A classic physiologic response to systemic hypoxia is the increase in red blood cell production. Hypoxia-inducible factors (HIFs) orchestrate oxygen-sensing machinery and hypoxic cell metabolism. Recent works suggest that mutation of the HIF oxygen-sensing pathway plays a key role in the pathogenesis of the erythrocytosis. In the present study, the probable role of the polymorphic HIF-1 alpha variants, C1772T (P582S) (rs11549465) and G1790A (A588T) (rs115494657), which are known to enhance transcriptional activity, were evaluated in the etiology of the polycythemia. Methods: A total of 284 subjects 97 with normal levels of hemoglobin (Hgb) 157 with high levels of Hgb, and 30 with polycythemia vera (PV)) were recruited for this study. Genomic DNA was extracted from peripheral blood lymphocytes of all subjects. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was performed for HIF-1 alpha C1772T and G1790A single nucletide polymorphisms (SNP). A complete blood count was performed for all subjects. Results: There was a significant decrease in the frequency of the HIF-1 alpha C1772T allele T in subjects with PV compared with those in the normal level Hgb group (OR 0.51; 95% CI 0.75-0.95; p=0.03). High level Hgb subjects had a significantly higher frequency of the HIF-1 alpha G1790A allele A (OR 10.79; 95% CI 0.62-; 187.96; p=0.027) than the subjects in the normal level Hgb group. A significant difference was observed in genotype distribution of GG and combined GA+AA genotypes of HIF-1 alpha G1790A in PV and normal Hgb level subjects (OR 17.11; 95% CI 0.80-366,61; p>0.05). Conclusion: Our results suggest that the HIF-1 alpha C1772T and G1790A polymorphisms may be associated with PV in the study population.