Genome-Wide Association Scan of Serum Urea in European Populations Identifies Two Novel Loci

Thio, Chris H L; Reznichenko, Anna; Most, Peter J. van der; Kamali, Zoha; Vaez, Ahmad; Smit, Johannes H.; Penninx, Brenda W.J.H.; Haller, Toomas; Mihailov, Evelin; Metspalu, Andres; Damman, Jeffrey; Borst, Martin H. de; Harst, Pim van der; Verweij, Niek; Navis, Gerjan; Gansevoort, Ron T.; Nolte, Ilja M.; Snieder, Harold

doi:10.1159/000496930

Cited by 6 publications

(3 citation statements)

References 40 publications

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“…Urea is the end product of protein catabolism in mammals, which is synthesized by the ornithine cycle in the liver and excreted mainly by the kidneys. Serum urea concentrations are highly variable and depend, in addition to renal function, on the liver and cardiac functions, dietary protein intake, metabolic rate, medication status, and hydration status ( 39 ). These factors are common in critically ill patients in the ICUs, which supports that the patient's physical condition is closely related to their survival.…”

Section: Discussionmentioning

confidence: 99%

Carbapenem-resistant Pseudomonas aeruginosa infections in critically ill children: Prevalence, risk factors, and impact on outcome in a large tertiary pediatric hospital of China

Huang

Wei²,

Xu³

et al. 2023

Front. Public Health

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Background and aimsCarbapenem-resistant Pseudomonas aeruginosa (CRPA) is a major cause of healthcare-associated infections worldwide, but comprehensive study of clinical characteristics for CRPA infections among critically ill children remains limited in China. The objective of this study was to determine the epidemiology, risk factors, and clinical outcomes of CRPA infections among critically ill pediatric patients in a large tertiary pediatric hospital in China.MethodsA retrospective case-control study of patients with P. aeruginosa infections was conducted in the three intensive care units (ICUs) of Shanghai Children's Medical Center from January 2016 to December 2021. All patients with CRPA infection in the ICUs were enrolled as case patients. Patients with carbapenem-susceptible P. aeruginosa (CSPA) infection were randomly selected as control patients in a ratio of 1:1. Clinical characteristics of those inpatients were reviewed through the hospital information system. Univariate and multivariate analyses were performed to evaluate risk factors associated with the development of CRPA infections and mortality of P. aeruginosa infections.ResultsA total of 528 cases of P. aeruginosa infection in the ICUs were enrolled in the 6-year study. The prevalence of CRPA and MDRPA (multidrug-resistance P. aeruginosa) was 18.4 and 25.6%, respectively. Significant risk factors related to CRPA infection were the length of hospitalization >28 days (OR = 3.241, 95% CI 1.622–6.473, p = 0.001), receiving invasive operations (OR = 2.393, 95% CI 1.196–4.788, p = 0.014) and a blood transfusion (OR = 7.003, 95% CI 2.416–20.297, p < 0.001) within 30 days before infection. Conversely, birth weight ≥2,500 g (OR = 0.278, 95% CI 0.122–0.635, p = 0.001) and breast nursing (OR = 0.362, 95% CI 0.168–0.777, p = 0.009) were significant protective factors against CRPA infections. The in-hospital mortality rate was 14.2%, and no difference in mortality was observed between patients with CRPA and CSPA infections. Platelet < 100 × 109/L (OR = 5.729, 95% CI 1.048–31.308, p = 0.044) and serum urea <3.2 mmol/L (OR = 5.173, 95% CI 1.215–22.023, p = 0.026) were independent predictors for the mortality due to P. aeruginosa infection.ConclusionsOur findings provide insights into CRPA infections among critically ill children in China. They provide guidance in identifying patients that may be at high risk for a resistant infection and emphasize the importance of antimicrobial stewardship and infection control in hospitals.

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Section: Discussionmentioning

confidence: 99%

Carbapenem-resistant Pseudomonas aeruginosa infections in critically ill children: Prevalence, risk factors, and impact on outcome in a large tertiary pediatric hospital of China

Huang

Wei²,

Xu³

et al. 2023

Front. Public Health

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“…The instrumental variables (IVs) were obtained from the Lifelines Cohort Study of 13,312 participants, of European ancestry, on serum urea [26]. The participants were genotyped using the SNP array and called by GenomeStudio (San Diego, CA, USA).…”

Section: Study Design and Data Sourcesmentioning

confidence: 99%

“…We employed the published instrumental variables associated with serum urea from GWAS [26]. The six selected SNPs were within or near the THBS3, LPP, ADAMTS9-AS2, PT-GER4, RSPO3 and POU2AF1 genes and reached a significant threshold (p-value < 5 × 10 −8 ) for their association with serum urea.…”

Section: Selection Of Instrumental Variablesmentioning

confidence: 99%

Causal Associations between Serum Urea and Cancer: A Mendelian Randomization Study

Sun

et al. 2021

Genes

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Urea is largely derived from the urea cycle reactions through hepatic detoxification of free ammonia and cleared by urination, and the serum urea level is a crucial medical indicator for measuring the kidney function in patients with nephropathy; however, investigative revelations pointing to the serum urea level as a risk factor for cancer are very scarce, and relevant studies are restricted by potential biases. We aimed to explore the causal relationships of the serum urea level with cancer development by focusing on renal cell carcinoma (RCC) using the Mendelian randomization (MR) analyses. Summary estimates were collected from the inverse-variance weighted (IVW) method based on six single nucleotide polymorphisms (SNPs). The selected SNPs related to the serum urea were obtained from a large genome-wide association study (GWAS) of 13,312 European participants. The summary statistics of RCC were also available from public databases (IARC, n = 5219 cases, n = 8011 controls). Sensitivity analyses included the weighted median and MR-Egger methods. Serum urea was inversely associated with RCC in females (effect = 1.93; 95% CI: 1.24 to 3.01; p = 0.004) but exhibited null association with RCC in males, breast cancer (BRCA) in both genders and prostate cancer (PCa) in males. Similar conclusions were also drawn from the weighted median and MR-Egger. These findings reveal an intriguing link between serum urea and cancer risks for the very first time. Without ambiguity, the serum urea is causatively related to RCC specifically in females, although the mechanism(s) by which urea is involved in RCC development remains to be experimentally/clinically investigated. Our studies may well provide novel insights for RCC diagnosis, intervention and/or therapy.

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The Role of the Transcriptional Coactivator BOB.1/OBF.1 in Adaptive Immunity

Betzler,

Brunner

2024

Transcription Factors in Blood Cell Development

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Genome-Wide Association Scan of Serum Urea in European Populations Identifies Two Novel Loci

Cited by 6 publications

References 40 publications

Carbapenem-resistant Pseudomonas aeruginosa infections in critically ill children: Prevalence, risk factors, and impact on outcome in a large tertiary pediatric hospital of China

Carbapenem-resistant Pseudomonas aeruginosa infections in critically ill children: Prevalence, risk factors, and impact on outcome in a large tertiary pediatric hospital of China

Causal Associations between Serum Urea and Cancer: A Mendelian Randomization Study

The Role of the Transcriptional Coactivator BOB.1/OBF.1 in Adaptive Immunity

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