Additional file 1: of Evidence for a protective role for the rs805305 single nucleotide polymorphism of dimethylarginine dimethylaminohydrolase 2 (DDAH2) in septic shock through the regulation of DDAH activity
Creators: name: Lambden, Simon
name: Tomlinson, James
name: Piper, Sophie
name: Gordon, Anthony
name: Leiper, James
Publisher: name: figshare
Year: 2018
Subjects: subject: Medicine
subject: Cell Biology
subject: Molecular Biology
subject: Physiology
subject: FOS: Biological sciences
subject: FOS: Biological sciences
subject: Pharmacology
subject: Biotechnology
subject: Immunology
subject: FOS: Clinical medicine
subject: FOS: Clinical medicine
subject: Cancer
subject: Science Policy
subject: 110309 Infectious Diseases
subject: FOS: Health sciences
subject: FOS: Health sciences
subject: 60506 Virology

description: Table S1. Median (IQR) peak concentrations of L-arginine, ADMA and SDMA (μM) in patients with septic shock categorised by treatment arm in the VANISH trial; p value for Kruskall-Wallis test, no intergroup differences detected on Dunn’s multiple comparison testing. Table S2. Pattern of plasma L-arginine concentrations over the first 7 days of the VANISH trial in survivors and non-survivors. Median (IQR) concentrations (μM). Table S3. Pattern of plasma ADMA concentrations over the first 7 days of the VANISH trial in survivors and non-survivors. Median (IQR) concentrations (μM). Table S4. Pattern of plasma SDMA concentrations over the first 7 days of the VANISH trial in survivors and non-survivors. Median (IQR) concentrations (μM). Table S5. Relationship between eight intronic SNPs of DDAH1 and mortality in septic shock. The prevalence of the rare genotype in each of the eight DDAH1 SNPs was noted. The odds ratio of death at 28 days after study inclusion was calculated for the common homozygotes against the combined heterozygote and rare homozygote populations. No significant differences in outcome were observed between the groups expressing the less common alleles and the common homozygotes. Figure S1. Plasma concentrations of L-arginine (A), ADMA (B) and SDMA (C) in septic shock and association with survival. Plasma from 249 patients with septic shock enrolled in the VANISH trial was collected collection on inclusion into the trial, which was prior to the start of vasopressor therapy (Day 0), and on days 3, 5 and 7 of the study. Dot plot (with median (IQR) overlay in black (survivors) or red (non-survivors)) comparing plasma concentrations on study inclusion and on days 3, 5 and 7 after study inclusion in survivors and non-survivors at 28 days after admission with septic shock. Median (IQR) plasma L-arginine concentrations were similar in non-survivors at each time point. Plasma ADMA and SDMA concentrations were higher in non-survivors at each time point. D Plasma SDMA concentration changes over the first 7 days of inclusion in the VANISH trial, notation describes the number of samples available for analysis at each time point. Median and interquartile range plotted in red. E Dot plot (with median (IQR) overlay in black (survivors) or red (non-survivors)) comparing plasma ADMA:L-arginine concentrations on study inclusion and on days 3, 5 and 7 after study inclusion in survivors and non-survivors at 28 days after admission with septic shock. Median (IQR) plasma ADMA:L-arginine concentrations appeared higher in non-survivors at days 3,5 and 7. Figure S2. Association between the rs805305 SNP of the DDAH2 promoter region and outcome in septic shock. Presence of the rare G:G homozygote was associated with a trend towards reduced hospital length of stay but was not statistically significant. Figure S3. Association between the rs805305 SNP of the DDAH2 promoter region and DDAH activity and outcome in septic shock. Plasma ADMA:SDMA ratio was elevated in the rare G:G genotype compared to the common C:C expression pattern, p = 0.004. (DOCX 3485 kb)