Journal article
Polymorphisms in α-Defensin-Encoding DEFA1A3 Associate with Urinary Tract Infection Risk in Children with Vesicoureteral Reflux
Journal of the American Society of Nephrology, Vol.27(10), pp.3175-3186
10/2016
DOI: 10.1681/ASN.2015060700
PMCID: PMC5042661
PMID: 26940096
Abstract
The contribution of genetic variation to urinary tract infection (UTI) risk in children with vesicoureteral reflux is largely unknown. The innate immune system, which includes antimicrobial peptides, such as the α-defensins, encoded by DEFA1A3, is important in preventing UTIs but has not been investigated in the vesicoureteral reflux population. We used quantitative real-time PCR to determine DEFA1A3 DNA copy numbers in 298 individuals with confirmed UTIs and vesicoureteral reflux from the Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) Study and 295 controls, and we correlated copy numbers with outcomes. Outcomes studied included reflux grade, UTIs during the study on placebo or antibiotics, bowel and bladder dysfunction, and renal scarring. Overall, 29% of patients and 16% of controls had less than or equal to five copies of DEFA1A3 (odds ratio, 2.09; 95% confidence interval, 1.40 to 3.11; P<0.001). For each additional copy of DEFA1A3, the odds of recurrent UTI in patients receiving antibiotic prophylaxis decreased by 47% when adjusting for vesicoureteral reflux grade and bowel and bladder dysfunction. In patients receiving placebo, DEFA1A3 copy number did not associate with risk of recurrent UTI. Notably, we found that DEFA1A3 is expressed in renal epithelium and not restricted to myeloid-derived cells, such as neutrophils. In conclusion, low DEFA1A3 copy number associated with recurrent UTIs in subjects in the RIVUR Study randomized to prophylactic antibiotics, providing evidence that copy number polymorphisms in an antimicrobial peptide associate with UTI risk.
Details
- Title: Subtitle
- Polymorphisms in α-Defensin-Encoding DEFA1A3 Associate with Urinary Tract Infection Risk in Children with Vesicoureteral Reflux
- Creators
- Andrew L Schwaderer - The Centers for Clinical and Translational Medicine andHuanyu Wang - The Centers for Clinical and Translational Medicine andSungHwan Kim - Departments of Biostatistics andJennifer M Kline - Emergency Medicine andDong Liang - Innate Immunity Translational Research Center, Children's Foundation Research Institute at Le Bonheur Children's Hospital, Memphis, TennesseePat D Brophy - Division of Nephrology, Department of Pediatrics, University of Iowa Children's Hospital, Iowa City, IowaKirk M McHugh - Division of Anatomy, The Ohio State University, Columbus, OhioGeorge C Tseng - Departments of Biostatistics andVijay Saxena - The Centers for Clinical and Translational Medicine andEvan Barr-Beare - The Centers for Clinical and Translational Medicine andKeith R Pierce - Innate Immunity Translational Research Center, Children's Foundation Research Institute at Le Bonheur Children's Hospital, Memphis, TennesseeNader Shaikh - Pediatrics, University of Pittsburgh, Pittsburgh, PennsylvaniaJ Robert Manak - Departments of Biology and Pediatrics, University of Iowa, Iowa; andDaniel M Cohen - Nationwide Children's HospitalBrian Becknell - The Centers for Clinical and Translational Medicine andJohn D Spencer - Nationwide Children's HospitalPeter B Baker - Department of Pathology, Nationwide Children's Hospital, Columbus, OhioChack-Yung Yu - Molecular and Human Genetics, The Research Institute at Nationwide Children's Hospital, Columbus, OhioDavid S Hains - Innate Immunity Translational Research Center, Children's Foundation Research Institute at Le Bonheur Children's Hospital, Memphis, Tennessee; Department of Pediatrics, University of Tennessee Health Science Center, Memphis, Tennessee dhains@uthsc.edu
- Resource Type
- Journal article
- Publication Details
- Journal of the American Society of Nephrology, Vol.27(10), pp.3175-3186
- DOI
- 10.1681/ASN.2015060700
- PMID
- 26940096
- PMCID
- PMC5042661
- NLM abbreviation
- J Am Soc Nephrol
- ISSN
- 1046-6673
- eISSN
- 1533-3450
- Publisher
- United States
- Grant note
- K08 DK094970 / NIDDK NIH HHS UL1 TR001878 / NCATS NIH HHS U01 DK074053 / NIDDK NIH HHS U01 DK074064 / NIDDK NIH HHS UL1 TR000005 / NCATS NIH HHS U01 DK074063 / NIDDK NIH HHS K08 DK102594 / NIDDK NIH HHS RC4 DK090937 / NIDDK NIH HHS U01 DK074059 / NIDDK NIH HHS UL1 RR024153 / NCRR NIH HHS U01 DK074062 / NIDDK NIH HHS UL1 TR000003 / NCATS NIH HHS U01 DK074082 / NIDDK NIH HHS
- Language
- English
- Date published
- 10/2016
- Academic Unit
- Stead Family Department of Pediatrics; Epidemiology; Biology; Craniofacial Anomalies Research Center
- Record Identifier
- 9983992094402771
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