Infection and Drug Resistance (Jan 2023)

Association of Single Nucleotide Polymorphisms in Nucleotide-Binding Domain Leucine-Rich Repeat Protein 1 with Clostridioides difficile Colonization or Infection

  • Tsai BY,
  • Tsai PJ,
  • Lee CC,
  • Chiu CW,
  • Lai YH,
  • Lee JC,
  • Ko WC,
  • Hung YP

Journal volume & issue
Vol. Volume 16
pp. 413 – 421

Abstract

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Bo-Yang Tsai,1,* Pei-Jane Tsai,1– 4,* Ching-Chi Lee,5,6 Chun-Wei Chiu,7 Yi-Hsin Lai,4 Jen-Chieh Lee,6 Wen-Chien Ko,6,8 Yuan-Pin Hung6– 9 1Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 2Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 3Department of Pathology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 4Centers of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan, Taiwan; 5Clinical Medicine Research Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 6Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 7Department of Internal Medicine, Tainan Hospital, Ministry of Health and Welfare, Tainan, Taiwan; 8Department of Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 9Department of Microbiology & Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan*These authors contributed equally to this workCorrespondence: Yuan-Pin Hung; Wen-Chien Ko, Department of Internal Medicine, Tainan Hospital, Ministry of Health and Welfare, Tainan, Taiwan, Email [email protected]; [email protected]: Nucleotide-binding domain leucine-rich repeat protein (NLRP) is critical in the inflammasome-activation pathway, which is important for host survival and the clearance of Clostridioides difficile. Therefore, the influence of NLRP1 polymorphisms on C. difficile colonization (CdC) or infection (CDI) was analyzed.Materials and Methods: A prospective cohort study consisted of hospitalized adults was conducted from January 2011 to January 2013. Single nucleotide polymorphisms (SNPs) of NLRP1, including rs12150220, rs2670660, rs6502867, rs878329, rs8182352, rs3744717, and rs11078571, were incorporating in analyses. The episodes of CdC and CDI were the primary and secondary outcome, respectively.Results: Of the total of 509 eligible patients, 376 (73.9%) had neither CdC nor CDI, 104 (21.8%) had CdC without developing CDI, and 29 (4.3%) developed CDI during the study period. Through multivariate analyses, comorbid diabetes mellitus (adjusted odds ratio [AOR] 1.59, P=0.04) and CC genotype in NLRP1 rs3744717 (AOR 1.70, P=0.02) were recognized as the risk factor of CdC. After adjusting the independent predictors of CDI, in terms of comorbid diabetes mellitus (AOR 3.18, P=0.005) and prior exposure to ceftazidime/ceftriaxone (AOR 2.87, P=0.04) or proton pump inhibitors (AOR 3.86, P=0.001), patients with CC+GC genotype in NLRP1, rs878329 (AOR 2.39, P=0.03) remained a higher risk of CDI.Conclusion: For hospitalized adults, the association of CC genotype in NLRP1 rs3744717 and CdC as well as the CC+GC genotype in NLRP1 rs878329 and CDI was respectively evidenced. We believed the prompt identification of patients having specific genotype in NLRP1 would prevent and improve the quality of care in CDI.Keywords: Clostridioides difficile infection, colonization, nucleotide-binding domain leucine-rich repeat protein 1, NLRP1, inflammasome, polymorphism

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