Ribonuclease 7 polymorphism rs1263872 reduces antimicrobial activity and associates with pediatric urinary tract...

Area of Science:

• Immunology
• Genetics
• Microbiology

Background:

• Ribonuclease 7 (RNase 7) is a key antimicrobial peptide protecting against urinary tract infections (UTIs).
• The impact of genetic variations in the RNASE7 gene on RNase 7's function and UTI susceptibility remains unclear.

Purpose of the Study:

• To investigate the prevalence of the RNASE7 single nucleotide polymorphism (SNP) rs1263872 in children with UTIs.
• To determine how the rs1263872 variant influences RNase 7's antimicrobial activity against uropathogenic Escherichia coli (UPEC).

Main Methods:

• Genotyping for rs1263872 was performed in two national pediatric UTI cohorts and compared to female controls.
• RNase 7 peptides and genetically modified urothelial cultures (wild-type and variant) were generated to assess antimicrobial activity.
• Urothelial cultures were used to evaluate the effect of RNase 7 variants on UPEC invasion.

Main Results:

• The RNASE7 variant rs1263872 was found to be more prevalent in girls with UTIs compared to controls.
• Wild-type RNase 7 peptide exhibited greater bactericidal activity against UPEC than the missense variant.
• Overexpression of wild-type RNase 7 in urothelial cultures significantly reduced UPEC invasive infection compared to the mutant variant.

Conclusions:

• Children with UTIs show a higher prevalence of the RNASE7 rs1263872 variant.
• This genetic variation may increase UTI susceptibility by impairing the antibacterial function of RNase 7.
• Targeting RNASE7 or its variants could offer new strategies for UTI prevention and treatment.