Genetic Susceptibility to Postdiarrheal Hemolytic-Uremic Syndrome After Shiga Toxin–Producing Escherichia coli Infection: A Centers for Disease Control and Prevention FoodNet Study

Kallianpur, Asha R.; Bradford, Yuki; Mody, Rajal K.; Garman, Katie N.; Comstock, Nicole; Lathrop, Sarah L.; Lyons, Carol; Saupe, Amy; Wymore, Katie; Canter, Jeffrey A.; Olson, Lana M.; Palmer, Amanda; Jones, Timothy F.

doi:10.1093/infdis/jix633

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Genetic Susceptibility to Postdiarrheal Hemolytic-Uremic Syndrome After Shiga Toxin–Producing Escherichia coli Infection: A Centers for Disease Control and Prevention FoodNet Study

3 05 2018
By Kallianpur, Asha R. ; Bradford, Yuki ; Mody, Rajal K. ; ...
http://dx.doi.org/10.1093/infdis/jix633
Source: J Infect Dis. 217(6):1000-1010

[PDF-867.34 KB]

English

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Details:

Alternative Title:

J Infect Dis
Personal Author:

Kallianpur, Asha R. ; Bradford, Yuki ; Mody, Rajal K. ; Garman, Katie N. ; Comstock, Nicole ; ... More +

Kallianpur, Asha R. ; Bradford, Yuki ; Mody, Rajal K. ; Garman, Katie N. ; Comstock, Nicole ; Lathrop, Sarah L. ; Lyons, Carol ; Saupe, Amy ; Wymore, Katie ; Canter, Jeffrey A. ; Olson, Lana M. ; Palmer, Amanda ; Jones, Timothy F. Less -
Description:

Background.

Postdiarrheal hemolytic-uremic syndrome (D+HUS) following Shiga toxin–producing Escherichia coli (STEC) infection is a serious condition lacking specific treatment. Host immune dysregulation and genetic susceptibility to complement hyperactivation are implicated in non–STEC-related HUS. However, genetic susceptibility to D+HUS remains largely uncharacterized.

Methods.

Patients with culture-confirmed STEC diarrhea, identified through the Centers for Disease Control and Prevention FoodNet surveillance system (2007–2012), were serotyped and classified by laboratory and/or clinical criteria as having suspected, probable, or confirmed D+HUS or as controls and underwent genotyping at 200 loci linked to nondiarrheal HUS or similar pathologies. Genetic associations with D+HUS were explored by multivariable regression, with adjustment for known risk factors.

Results.

Of 641 enrollees with STEC O157:H7, 80 had suspected D+HUS (41 with probable and 32 with confirmed D+HUS). Twelve genes related to cytokine signaling, complement pathways, platelet function, pathogen recognition, iron transport, and endothelial function were associated with D+HUS in multivariable-adjusted analyses (P ≤ .05). Of 12 significant single-nucleotide polymorphisms (SNPs), 5 were associated with all levels of D+HUS (intergenic SNP rs10874639, TFRC rs3804141, EDN1 rs5370, GP1BA rs121908064, and B2M rs16966334), and 7 SNPs (6 non–complement related) were associated with confirmed D+HUS (all P < .05).

Conclusions.

Polymorphisms in many non–complement-related genes may contribute to D+HUS susceptibility. These results require replication, but they suggest novel therapeutic targets in patients with D+HUS.
Subjects:

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Adolescent Centers For Disease Control And Prevention, U.S. Child Child, Preschool Diarrhea Escherichia Coli Infections Female Genetic Predisposition To Disease Hemolytic-Uremic Syndrome Humans Male Risk Factors Shiga-Toxigenic Escherichia Coli United States
Keywords:

[+]

Diarrheal HUS Foodborne Illness Genetic Variant Shiga Toxin STEC Typical Hemolytic-uremic Syndrome Verocytotoxin
Source:

J Infect Dis. 217(6):1000-1010
Pubmed ID:

29216383
Pubmed Central ID:

PMC11318523
Document Type:

Journal Article
Funding:

CC999999/ImCDC/Intramural CDC HHSUnited States/ ; U50 CK000315/CK/NCEZID CDC HHSUnited States/

CC999999/ImCDC/Intramural CDC HHSUnited States/ ; U50 CK000315/CK/NCEZID CDC HHSUnited States/ Less -
Collection(s):

CDC Public Access
Main Document Checksum:

[+]

urn:sha-512:c2f958be428d3c214f84d6fbee8cc983516b8b01fb2546a888ba8761852e02454d7049ebfbbf542b592ff8cd7382701e5f63c1969f4c7273890f926327cdf443
Download URL:

https://stacks.cdc.gov/view/cdc/159827/cdc_159827_DS1.pdf
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