097: Comparison of Hypoxia Inducible Factor-1A Polymorphisms Between Chronic Kidney Disease Patients & Healthy Subjects

Statement of Purpose, Innovation or Hypothesis: Hypoxia-inducible factor 1 (HIF-1) is an important factor in oxygen homeostasis and has been shown to promote tissue response in hypoxic chronic kidney disease (CKD) conditions. HIF-1 is a heterodimeric protein complex. It has two subunits, alpha and beta. The alpha subunit dimerizes with the beta and forms the HIF-1 molecule in the hypoxic condition. HIF-1 is abundant in the kidneys, and previous studies illustrate that HIF-1A polymorphism is correlated with various kidney conditions. Prolyl Hydroxylase inhibitors (PHD-I) that target HIF-1A  have been approved for anemia of CKD.  Potential polymorphism in HIF-1A can affect the efficacy of PHD-I. In this study, we aim to identify particular polymorphisms in HIF-1A that may be more prevalent in CKD patients compared to healthy controls.

Description of Methods & Materials: This study was approved by the Shenandoah Univ IRB committee. After obtaining the participants’ consent, DNA samples were obtained for genetic testing using oral swabs. Forty-eight healthy individuals were recruited in the control group.  Participants’ eGFR and SrCr were collected from their latest lab results. In collaboration with our affiliated kidney and hypertension specialist clinic, ninety patients with CKD stage II-V were recruited. Patient eGFR and SrCr values were obtained from electronic medical records.  DNA samples were extracted using the QIAamp MinElute Virus Spin Kit protocol for plasma samples or QIAcube blood mini kit for buccal swabs and quantified using PicoDrop. Genotyping was done using Applied Biosystems Taqman assays and Quantstudio-6 PCR analysis for three known SNPs (rs1951795, rs1957757 and rs11549465) in the HIF-1A gene. Genotype frequencies were compared between patients with CKD and healthy individuals.

Data & Results: Among the three SNPs we studied, differences were found between the patient and control groups for rs1951795 SNP. The homozygous variant (A/A) genotype had a higher frequency in the patient group compared to control (Relative risk =9.0250,95% CI 14.004 to 2.849, p-value: 0.0289). In contrast, for the rs1957757 SNP, the heterozygous variant (C/T) genotype had a significantly higher frequency in healthy subjects compared to the patient group (Relative risk= 0.5643, 95% CI 2.431 to 16.059, p-value: 0.0093).  No significant differences were found in the heterozygous genotype frequency of  rs11549465 polymorphism between CKD and control groups.

Interpretation, Conclusion or Significance: We report that the frequencies of the homozygous variant (A/A) genotype of rs1951795 and the heterozygous (C/T) variant genotype of rs1957757 have the potential to be associated with CKD.

Disclosures: Shahrzad Ashena: Nothing to disclose. Hanifa Aktar: Nothing to disclose. Shahrzad Movafagh: Nothing to disclose. Acknowledgment: Debbie Lynn.

Citations/References: 1. Semenza GL. Hydroxylation of HIF-1: oxygen sensing at the molecular level. Physiology (Bethesda) 2004 Aug;19:176-82 . 2. Kolyada AY, Tighiouart H, Perianayagam MC, Liangos O, Madias NE, Jaber BL. A genetic variant of hypoxia-inducible factor-1alpha is associated with adverse outcomes in acute kidney injury. Kidney Int 2009 Jun;75(12):1322-1329.

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