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

Abstract

Introduction

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

Data Sharing Statement

The original contributions presented in the study are included in the article/Supplementary Materials. Further inquiries can be directed to the corresponding author.

Disclosure

All authors report no conflicts of interest relevant to this article.

Additional information

Funding

The present study was supported by research grants from the Ministry of Science and Technology, Taiwan (109-2314-B-006-089-MY3, 110-2320-B-006-024 and 110-2314-B-675-001), Ministry of Health and Welfare, Taiwan (MOHW 110-TDU-B-211-124003), and National Cheng Kung University Hospital, Tainan, Taiwan (NCKUH-11004029).