Interleukin-8 and CXCR1 Receptor Functional Polymorphisms and Susceptibility to Acute Pyelonephritis
We performed a case-control study in children diagnosed by the first episode of upper urinary tract infection with or without vesicoureteral reflux to evaluate the association of functional polymorphism of interleukin-8 (−251A>T and +2767A>G), and its receptor CXCR1 (+2607G>C).
Materials and Methods:
Genomic DNA was obtained from 265 children with a clinical and laboratory diagnosis of urinary tract infection who were recruited in northeast Italy. The children were subdivided as 173 who were dimercapto-succinic acid scan positive with positive static renal scintigraphy in acute conditions, consistent with the diagnosis of acute pyelonephritis, and 92 who were dimercapto-succinic acid scan negative. Genetic analysis for the same polymorphisms was also extended to a control population of 106 umbilical cord DNA samples.
Statistical analysis of genotype data showed that 1) the tested populations were in Hardy-Weinberg equilibrium, 2) there were significant differences between the dimercapto-succinic acid scan positive and negative groups (p = 0.049), and the dimercapto-succinic acid scan positive group vs controls (p = 0.032) in terms of interleukin-8 −251A>T polymorphism frequency, 3) there was also a significant difference in the distribution of IL-8 −251A>T and +2767A>G polymorphisms between dimercapto-succinic acid scan positive and negative children in the subgroup without vesicoureteral reflux (p = 0.03 and 0.02, respectively) and 4) no significant differences were found in the frequency of the distribution of CXCR1 +2607G>C polymorphism in all groups.
These data suggest that the gene for the proinflammatory chemokine interleukin-8 is involved in susceptibility to acute pyelonephritis during upper urinary tract infection in children with or without vesicoureteral reflux.
- 1 : Morbidity, age and sex distribution, recurrences, and renal scarring in symptomatic urinary tract infection in childhood. Kidney Int1975; 8: S101. Google Scholar
- 2 : Cytokine profiles of pediatric patients treated with antibiotics for pyelonephritis: potential therapeutic impact. Clin Diagn Lab Immunol2001; 8: 1060. Google Scholar
- 3 : Incidence rate of first-time symptomatic urinary tract infection in children under 6 years of age. Acta Paediatr1998; 87: 549. Google Scholar
- 4 : Long-term prognosis of post-infectious renal scarring in relation to radiological findings in childhood—a 27 year follow-up. Pediatr Nephrol1992; 6: 19. Google Scholar
- 5 : Relationship between acute pyelonephritis, renal scarring, and vesicoureteral reflux. Pediatr Nephrol2004; 19: 1122. Google Scholar
- 6 : Childhood urinary tract infection: a clinical analysis of 597 cases. Acta Paediatr Taiwan2004; 45: 313. Google Scholar
- 7 : ACE gene polymorphism and renal scar in children with acute pyelonephritis. Pediatr Nephrol2002; 17: 491. Google Scholar
- 8 : Association of transforming growth factor-β1 gene polymorphism with reflux nephropathy. J Urol2005; 174: 1609. Link, Google Scholar
- 9 : Association between RANTES promoter polymorphism –401A and enhanced RANTES production in atopic dermatitis patients. J Dermatol Sci2005; 39: 189. Google Scholar
- 10 : Elevated interleukin-8 levels in the urine of patients with urinary tract infections. Infect Immun1993; 61: 1307. Google Scholar
- 11 : Escherichia coli-induced expression of IL-1 alpha, IL-1 beta, IL-6 and IL-8 in normal human renal tubular epithelial cells. Clin Exp Immunol2001; 124: 423. Google Scholar
- 12 : Interleukin-8 receptor deficiency confers susceptibility to acute pyelonephritis. J Infect Dis2001; 183: S56. Google Scholar
- 13 : Single nucleotide polymorphisms in the coding regions of human CXC-chemokine receptors CXCR1, CXCR2 and CXCR3. Genes Immun2000; 1: 330. Google Scholar
- 14 : Unusual haplotypic structure of IL8, a susceptibility locus for a common respiratory virus. Am J Hum Genet2001; 69: 413. Google Scholar
- 15 : Interleukin 8 gene polymorphism is associated with increased risk of nephritis in cutaneous vasculitis. J Rheumatol2002; 29: 2367. Google Scholar
- 16 : Association study suggests opposite effects of polymorphisms within IL8 on bronchial asthma and respiratory syncytial virus bronchiolitis. J Allergy Clin Immunol2004; 114: 671. Google Scholar
- 17 : Increased in vivo transcription of an IL-8 haplotype associated with respiratory syncytial virus disease-susceptibility. Genes Immun2004; 5: 274. Google Scholar
- 18 : Review: nomenclature and biologic significance of cytokines involved in inflammation and the host immune response. J Infect Dis1995; 172: 1573. Google Scholar
- 19 : A novel interleukin-8 polymorphism is associated with severe systemic lupus erythematosus nephritis. Kidney Int2002; 62: 261. Google Scholar
- 20 : The 3′-untranslated region of human interleukin-8 mRNA suppresses IL-8 gene expression. Immunology2001; 102: 498. Google Scholar
University of Padova, Padova, Italy