Hypoxia Inducible Factor-2 Alpha and Prolinhydroxylase 2 Polymorphisms in Patients with Acute Respiratory Distress Syndrome (ARDS).

Hypoxia-inducible-factor-2α (HIF-2α) and HIF-2 degrading prolyl-hydroxylases (PHD) are key regulators of adaptive hypoxic responses i.e., in acute respiratory distress syndrome (ARDS). Specifically, functionally active genetic variants of (single nucleotide polymorphism (SNP) [ch2:46441523(hg18)]) and (C/T; SNP rs516651 and T/C; SNP rs480902) are associated with improved adaptation to hypoxia i.e., in high-altitude residents. However, little is known about these SNPs' prevalence in Caucasians and impact on ARDS-outcome. Thus, we tested the hypotheses that in Caucasian ARDS patients SNPs in or genes are (1) common, and (2) independent risk factors for 30-day mortality. After ethics-committee approval, 272 ARDS patients were prospectively included, genotyped for (Taqman SNP Genotyping Assay) and -polymorphism (restriction digest + agarose-gel visualization), and genotype dependent 30-day mortality was analyzed using Kaplan-Meier-plots and multivariate Cox-regression analyses. Frequencies were 99.62% for homozygous CC-carriers (CG: 0.38%; GG: 0%), 2.3% for homozygous SNP rs516651 TT-carriers (CT: 18.9%; CC: 78.8%), and 3.7% for homozygous SNP rs480902 TT-carriers (CT: 43.9%; CC: 52.4%). rs516651 TT-genotype in ARDS was independently associated with a 3.34 times greater mortality risk (OR 3.34, CI 1.09-10.22; = 0.034) within 30-days, whereas the other SNPs had no significant impact ( = ns). The homozygous GG-genotype was not present in our Caucasian ARDS cohort; however SNPs exist in Caucasians, and rs516651 TT-genotype was associated with an increased 30-day mortality suggesting a relevance for adaptive responses in ARDS.