Genome-wide association study of Klebsiella pneumoniae urinary tract infection in Taiwanese patients identifies potential genetic risk factors

Abstract

Background Urinary tract infections (UTI) are the most common bacterial infections worldwide, and Klebsiella pneumoniae (K. pneumoniae) UTI are a notable issue worldwide, especially in Taiwan. This is not only because of the association with immunocompromised patients, but also because of the issue of antibiotic resistance caused by K. pneumoniae. Therefore, the aim of this study was to identify possible risk factors in the genomes of Taiwanese patients with K. pneumoniae UTI using genome-wide association studies (GWASs). Methods Genotyping results were collected from participants recruited from Tri-Service General Hospital who had a medical history of urinary tract infection and joined the Taiwan Precision Medicine Initiative (TPMI). A case-control study was designed using GWAS to identify possible susceptibility single-nucleotide polymorphisms (SNPs) in patients with K. pneumoniae infected UTI. The corresponding genes were identified using the genome browser, and their expression profiles were confirmed using the GTEx database. To determine the relationship between these genes and biological function, molecular pathway and diseases, we also searched the GO, Rectome, DisGeNET, and MalacCards databases. Results The GWAS analysis identified 11 variants with a higher odds ratio than the control groups. These variants are involved in adhesion, protein depolymerization, Ca2+-activated potassium channels, SUMOylation, and protein ubiquitination, which might further impact the host immune response. Disease association analysis based on these risk variants also revealed several diseases that were compatible with the medical histories of the included patients. Conclusion This GWAS study based on the Taiwanese population suggests the idea that some risk variants may be associated with K. pneumoniae infection by affecting various molecular functions that could impact host immunity. Further studies and follow-up are required to clarify the impact of these risk variants on infectious diseases.