Genetic variations of interleukin‐8, CXCR1 and CXCR2 genes and risk of acute pyelonephritis in children

Abstract

Acute pyelonephritis (APN) is the most severe form of urinary tract infection, the etiopathogenesis of which is still not well understood. Previous studies demonstrated that chemotaxis of neutrophils into the tissue and across the infected epithelial layer is a key step in rapid bacterial clearance. Variations within genes encoding the major chemokine interleukin-8 and its receptors CXCR1 and CXCR2 are therefore attractive candidates for participation in genetic predisposition to APN. The aim of our study was to evaluate the association of single nucleotide polymorphisms (SNPs) -251 T/A, +781 C/T, +1633 C/T and +2767 A/T in the IL-8 gene, +2608 G/C in the CXCR1 gene and +1208 C/T in the CXCR2 gene with susceptibility to APN in the Slovak population. PCR-SSP and PCR-RFLP were used to genotype SNPs in 147 children with APN (62 with recurrent and 85 with episodic form) and 215 healthy individuals. Statistical analysis revealed significantly increased frequency of CXCR1 +2608 C allele (P = 0.0238, OR = 2.452, 95% CI = 1.147-5.243) and GC genotype (P = 0.0201, OR = 2.627, 95% CI = 1.188-5.810) and lower frequency of CXCR2 +1208 T allele (P = 0.0408, OR = 0.645, 95% CI = 0.429-0.972) and TT+TC genotypes (P = 0.0497, OR = 0.5273, 95% CI = 0.288-0.964) in patients with recurrent APN compared with healthy controls. Furthermore, the A allele of IL-8 -251 T/A SNP was also significantly overrepresented in patients with recurrent APN when compared with those with only single episode of APN (P = 0.0439, OR = 1.627, 95% CI = 1.019-2.599). Our results indicate that the minor CXCR1 +2608 C allele is associated with significantly increased susceptibility to APN in childhood, while the CXCR2 +1208 T allele confers protection from recurrent APN. Moreover, allele A of the IL-8 -251 T/A may also increase the risk of developing recurrent attacks after the first-time APN.

CXCR1-mediated neutrophil degranulation and fungal killing promote Candida clearance and host survival

“…The mutant CXCR1-T276 SNP, which has been associated with increased susceptibility to bacterial renal infection in two independent cohorts of pediatric patients (14,15), provided a unique translational opportunity to extend our mouse findings to humans. Hence, we found that the CXCR1-T276 allele is associated with an increased likelihood for the development of disseminated candidiasis in candidemic patients of mixed European descent.…”

Distribution of CXCR2 +1208 T/C gene polymorphisms in relation to opportunistic infections among HIV-infected patients in Limpopo Province, South Africa

“…In a case-control study involving breast cancer patients with invasive ductal carcinoma, the CXCR2 +1208 C/T polymorphism showed no differences between studied groups (Kamali-Sarvestani et al, 2007). In a study conducted in Slovakia, the CXCR2 +1208 T allele was the least represented in that community and conferred protection from recurrent acute pyelonephritis (APN), which is the most severe form of urinary tract infection (Javor et al, 2012). Because of the limited number of participants in our study, further studies are necessary to confirm these results.…”

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

“…Two hundred and eighty‐four publications were retrieved from electronic databases. Eight studies met our inclusion and exclusion criteria, of which seven reported CXCR1 rs2234671 and two reported CXCR1 rs3138060 . Detailed genetic frequencies of CXCR1 rs16858808, CXCR2 1126579, and rs4674258 were reported in one article each (Fig.…”

“…As an example, Gond et al did not find any association between CXCR1 rs2234671 polymorphism and UTI susceptibility in adults, whereas Yin et al reported that rs2234671 GC genotype and C allele have lower prevalence in UTI sufferers than in controls . These paradoxical results were also observed in children …”