Association between interleukin 8‐receptor gene (CXCR1 and CXCR2) polymorphisms and urinary tract infection: Evidence from 4097 subjects

Han, Shisheng; Lu, Yan; Chen, Min; Xu, Yawei; Wang, Yi

doi:10.1111/nep.13260

Cited by 10 publications

(9 citation statements)

References 33 publications

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“…Recently, Han and colleagues ( 68 ) performed a meta-analysis of articles concerning CXCR1 SNPs rs2234671 and rs3138060 published until the end of 2017. Their results showed no evidence of correlation between CXCR1 rs2234671 polymorphism and susceptibility for UTI in adults, but found a significantly increased risk of UTI in children carrying rs2234671 .…”

Section: Resultsmentioning

confidence: 99%

A Systematic Review of the (Un)known Host Immune Response Biomarkers for Predicting Recurrence of Urinary Tract Infection

Hosman

Roić²,

Lamot³

2022

Front. Med.

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Recurrent urinary tract infections (rUTI) represent a major healthcare and economic burden along with a significant impact on patient’s morbidity and quality of life, even in the absence of well-known risk factors, such as vesicoureteral reflux. Despite numerous attempts to find a suitable therapeutic option, there is no clear benefit of any currently available intervention for prevention of UTI recurrence and its long-term consequences such as hypertension, renal scarring and/or insufficiency. The common treatment practice in many centers around the globe involves the use of continuous low-dose antibiotic prophylaxis, irrespective of various studies indicating increased microbial resistance against the prophylactic drug, leading to prolonged duration and escalating the cost of UTI treatment. Moreover, the rapid appearance of multi-drug resistant uropathogens is threatening to transform UTI to untreatable disease, while impaired host-microbiota homeostasis induced by a long-term use of antibiotics predisposes patients for various autoimmune and infectious diseases. New biomarkers of the increased risk of UTI recurrence could therefore assist in avoiding such outcomes by revealing more specific patient population which could benefit from additional interventions. In this light, the recent findings suggesting a crucial role of urothelial innate immunity mechanisms in protection of urinary tract from invading uropathogens might offer new diagnostic, prognostic and even therapeutic opportunities. Uroepithelial cells detect uropathogens via pattern recognition receptors, resulting in activation of intracellular signaling cascade and transcription factors, which ultimately leads to an increased production and secretion of chemokines, cytokines and antimicrobial peptides into the urinary stream. Emerging evidence suggest that the disturbance of a single component of the urinary tract innate immunity system might increase susceptibility for rUTI. The aim of the current review is to update clinicians and researchers on potential biomarkers of host immune response alterations predisposing for rUTI and propose those well worth exploring further. For this purpose, over a hundred original papers were identified through an extensive PubMed and Scopus databases search. This comprehensive review might enrich the current clinical practice and fill the unmet clinical needs, but also encourage the development of therapeutic agents that would facilitate urinary bacterial clearance by enhancing the host immune response.

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Section: Resultsmentioning

confidence: 99%

A Systematic Review of the (Un)known Host Immune Response Biomarkers for Predicting Recurrence of Urinary Tract Infection

Hosman

Roić²,

Lamot³

2022

Front. Med.

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“…CXCR1 and CXCR2 are specific receptors for IL-8, which plays a role in recruiting neutrophils and bacterial clearance [ 19 ]. Rs2234671 causes the amino acid serine to replace threonine at amino acid residue 276 of the CXCR1 protein [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

VDR, CXCR1, CXCR2, PSCA Polymorphisms and Recurrent Urinary Tract Infections in Women: Genetic Association Study

Sarker,

Pereira,

Khullar

et al. 2024

Int Urogynecol J

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Introduction and hypothesis Urinary tract infection (UTI) is one of the most common human infections. Evidence suggests that there might be a genetic predisposition to UTI. Previous small candidate gene studies have suggested that common variants in genes involved in the immune response to UTI could increase susceptibility to the development of recurrent UTI (rUTI). The objective was to conduct a gene association study to replicate previous gene association studies identifying single nucleotide polymorphisms (SNPs) putatively associated with rUTI in adult women. Methods Women with a history of rUTI and healthy controls were recruited (n = 1,008) from gynaecology outpatient clinics. Participants completed a signed consent form and questionnaire for phenotyping. DNA was extracted from blood or saliva samples for each participant. Putative associated SNPs were identified from a comprehensive systematic review of prior gene association studies. Primers for each selected SNP were designed, and genotyping was conducted using a competitive polymerase chain reaction (PCR) method. The Chi-squared test was used to assess the association between each variant and rUTI. Genotyping quality was assessed by checking for deviation from Hardy–Weinberg equilibrium. Results We found no association between SNPs tested in the VDR (p = 0.16, p = 0.09, p = 0.36), CXCR1 (p = 0.09), CXCR2 (p = 0.39), PSCA (p = 0.74) genes, and rUTI in adult women. Conclusions To our knowledge, this is the largest study to date, finding no significant associations. Previously reported positive associations may have been due to type 1 error, or genotyping errors. Future studies should adjust for confounders and employ adequate sample sizes. A greater understanding of the genetic components associated with rUTI may influence future treatment guidelines and screening for susceptible patients.

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“…Last, but not least, CXC chemokines and their receptors have an important role in providing an inflammatory local response to UTIs [ 24 ]. Polymorphisms in the interleukin 8-receptor (CXCR1), which is a crucial chemokine receptor involved in neutrophil recruitment, and, therefore, in an optimal function of the innate immune system, can be associated with UTIs, especially in children [ 25 , 26 ]. However, more research is needed, as evidence is conflicting [ 27 ].…”

Section: Genetic and Immunological Aspectsmentioning

confidence: 99%

Chronic Kidney Disease, Urinary Tract Infections and Antibiotic Nephrotoxicity: Are There Any Relationships?

et al. 2022

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Chronic kidney disease (CKD) has been a constant burden worldwide, with a prevalence of more than 10% of the population and with mortality reaching 1.2 million deaths and 35.8 million disability-adjusted life years (DALYs) in 2017, as it is claimed by the Global Burden of Diseases. Moreover, an increase in its prevalence is expected in the next years due to a rise in the number of people suffering from obesity, diabetes mellitus and hypertension. On the other hand, with cardiovascular morbidity and mortality showing a downward trend, maybe it is time to focus on CKD, to minimize the preventable risk factors involved in its progression toward end-stage kidney disease (ESKD) and to offer a better quality of life. Another major health burden is represented by infectious diseases, particularly urinary tract infections (UTIs), as it is considered that approximately 40–50% of women and 5% of men will have at least one episode during their lifetime. Additionally, CKD consists of a constellation of immunological and metabolical disturbances that lead to a greater risk of UTIs: increased apoptosis of lymphocytes, elevated levels of tumor necrosis factor α and interleukin 6, which lower the function of neutrophils and increased levels of uremic toxins like p-cresyl sulfate and indoxyl sulfate, which alter the adherence and migration of leukocytes to the sites of injury. Moreover, UTIs can lead to a more rapid decline of kidney function, especially in stages G3-G5 of CKD, with all the complications involved. Last, but not least, antibiotherapy is often complicated in this category of patients, as antibiotics can also negatively affect the kidneys. This review will try to focus on the particularities of the urinary microbiome, asymptomatic bacteriuria and UTIs and the subtle balance between the risks of them and the risks of antibiotherapy in the evolution of CKD.

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Association between interleukin 8‐receptor gene (CXCR1 and CXCR2) polymorphisms and urinary tract infection: Evidence from 4097 subjects

Cited by 10 publications

References 33 publications

A Systematic Review of the (Un)known Host Immune Response Biomarkers for Predicting Recurrence of Urinary Tract Infection

A Systematic Review of the (Un)known Host Immune Response Biomarkers for Predicting Recurrence of Urinary Tract Infection

VDR, CXCR1, CXCR2, PSCA Polymorphisms and Recurrent Urinary Tract Infections in Women: Genetic Association Study

Chronic Kidney Disease, Urinary Tract Infections and Antibiotic Nephrotoxicity: Are There Any Relationships?

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