The genotype distributions and allele frequencies in 167 patients for eNOS G894T (rs1799983) and in 166 patients for iNOS G2087A (rs2297518) out of 172 patients with acute Puumala hantavirus infection^*.

<p>Abbreviations: eNOS = endothelial nitride oxide synthase, iNOS = inducible nitride oxide synthase.</p><p>*The genotyping was successful in 167 patients for eNOS and in 166 patients for iNOS.</p><p>The genotype distributions and allele frequencies in 167 patients for eNOS G894T (rs1799983) and in 166 patients for iNOS G2087A (rs2297518) out of 172 patients with acute Puumala hantavirus infection<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0142872#t002fn002" target="_blank">^*</a>.</p

Endothelial Nitric Oxide Synthase G894T Polymorphism Associates with Disease Severity in Puumala Hantavirus Infection

<div><p>Introduction</p><p>Hantavirus infections are characterized by both activation and dysfunction of the endothelial cells. The underlying mechanisms of the disease pathogenesis are not fully understood. Here we tested the hypothesis whether the polymorphisms of endothelial nitric oxide synthase, eNOS G894T, and inducible nitric oxide synthase, iNOS G2087A, are associated with the severity of acute Puumala hantavirus (PUUV) infection.</p><p>Patients and Methods</p><p>Hospitalized patients (n = 172) with serologically verified PUUV infection were examined. Clinical and laboratory variables reflecting disease severity were determined. The polymorphisms of eNOS G894T (Glu298Asp, rs1799983) and iNOS G2087A (Ser608Leu, rs2297518) were genotyped.</p><p>Results</p><p>The rare eNOS G894T genotype was associated with the severity of acute kidney injury (AKI). The non-carriers of G-allele (TT-homozygotes) had higher maximum level of serum creatinine than the carriers of G-allele (GT-heterozygotes and GG-homozygotes; median 326, range 102–1041 vs. median 175, range 51–1499 μmol/l; p = 0.018, respectively). The length of hospital stay was longer in the non-carriers of G-allele than in G-allele carriers (median 8, range 3–14 vs. median 6, range 2–15 days; p = 0.032). The rare A-allele carriers (<i>i</i>.<i>e</i>. AA-homozygotes and GA-heterozygotes) of iNOS G2087A had lower minimum systolic and diastolic blood pressure than the non-carriers of A-allele (median 110, range 74–170 vs.116, range 86–162 mmHg, p = 0.019, and median 68, range 40–90 vs. 72, range 48–100 mmHg; p = 0.003, respectively).</p><p>Conclusions</p><p>Patients with the TT-homozygous genotype of eNOS G894T had more severe PUUV-induced AKI than the other genotypes. The eNOS G894T polymorphism may play role in the endothelial dysfunction observed during acute PUUV infection.</p></div

Box plots of the maximum plasma creatinine (A), hematocrit (B) and leukocyte count in TT-homozygotes (n = 10) and GT-heterozygotes or GG-homozygotes (n = 157) of eNOS G894T(rs1799983) polymorphism in 169 patients with PUUV infection.

<p>Box plot illustrates median (thick line inside box), 25^th and 75^th percentiles (box), and range (whiskers). Extremes and outliers have been omitted from the figure.</p

Additional file 2: of Central wave reflection is associated with peripheral arterial resistance in addition to arterial stiffness in subjects without antihypertensive medication

Spearman’s correlation matrix for the haemodynamic variables and age. (DOCX 14.5 KB

The clinical and laboratory findings in 172 patients with acute Puumala hantavirus infection.

<p>Abbreviation: CRP, C-reactive protein.</p><p>Normal values: CRP < 10 mg/ml, creatinine ≤ 100 μmol/l for males and ≤ 90 μmol/l for females, platelet count 150–360 x 10⁹/l, leukocyte count 3.4–8.2 x 10⁹/l, hematocrit 0.35–0.50 for males and 0.35–0.46 for females.</p><p>*Equals to the onset of illness before the first blood test was taken.</p><p>**Change in weight during hospital stay reflects the fluid accumulation in the body during the oliguric phase.</p><p>The clinical and laboratory findings in 172 patients with acute Puumala hantavirus infection.</p

Qualitative analysis of plasma cf-DNA in 10 patients with maximum plasma creatinine >370 µmol/l (A) and 10 patients with maximum plasma creatinine <125 µmol/l (B) after NucleoSpin® Plasma XS kit extraction.

<p>Analyses were performed with Agilent's High Sensitivity Lab-on-a-chip DNA assay. Green lines indicate the low weight (35 base pairs (bp)) DNA marker and purple lines the high weight (10 380 bp) DNA marker. The intensity of low-molecular weight cf-DNA band was graded as follows: 1 = no visible cf-DNA or weak band intensity, 2 = intermediate band intensity, 3 = strong band intensity.</p

Laboratory data for 61 patients with Puumala hantavirus infection.

<p>Min = minimum, Max = maximum, CRP = plasma C-reactive protein, IL-6 = plasma inteleukin-6, IDO = serum kynurenine/tryptophan ratio.</p

Clinical data for 61 patients with Puumala hantavirus infection.

<p>BMI = body mass index, min = minimum, max = maximum</p

Qualitative analysis of urine cf-DNA after NucleoSpin® Plasma XS kit extraction.

<p>Analyses were performed with Agilent's High Sensitivity Lab-on-a-chip DNA assay. Green lines indicate the low weight (35 base pairs (bp)) DNA marker and purple lines the high weight (10 380 bp) DNA marker. During the acute phase of the disease low-molecular weight (150–200 bp) pattern of cf-DNA was detected only in patients no 5 and 7, while patients no 3 and 20 had random-sized cf-DNA fragments in their control urine samples. Data from patients no 11 and 14 are depicted as examples of the 16 subjects who had no findings in the urinary cf-DNA fragment analyses.</p

Additional file 2: of Genome-wide association study of nocturnal blood pressure dipping in hypertensive patients

Table S1. Covariates used for calculation of night-to-day blood pressure ratio residuals in GENRES. Table S2. Meta-analysis of blood pressure dipping (night-to-day blood pressure ratio) in all three studies (n = 567). Table S3. Association of SNPs of circadian genes with blood pressure dipping (night-to-day blood pressure ratio) in GENRES. Table S4. Association of circadian genes with blood pressure dipping (night-to-day blood pressure ratio) in GENRES. Table S5. Replication of SNPs previously associated with blood pressure dipping in GENRES. Table S6. Functional analysis of the lead SNPs associated with blood pressure dipping (night-to-day blood pressure ratio) in GENRES GWAS. Table S7. Association of the top blood pressure dipping SNPs with selected UK Biobank GWAS phenotypes. (XLS 167 kb