RGD Reference Report - Genetic variations of interleukin-8, CXCR1 and CXCR2 genes and risk of acute pyelonephritis in children. - Rat Genome Database

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

Authors: Javor, J  Bucova, M  Cervenova, O  Kralinsky, K  Sadova, E  Suchankova, M  Liptakova, A 
Citation: Javor J, etal., Int J Immunogenet. 2012 Aug;39(4):338-45. doi: 10.1111/j.1744-313X.2012.01096.x. Epub 2012 Feb 10.
RGD ID: 7207860
Pubmed: PMID:22325052   (View Abstract at PubMed)
DOI: DOI:10.1111/j.1744-313X.2012.01096.x   (Journal Full-text)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CXCL8Humanacute pyelonephritis susceptibilityIAGP DNA:SNP:promoter:g.-251T>A (rs4073) (human)RGD 
CXCR2Humanacute pyelonephritis susceptibilityIAGP DNA:polymorphism:3' utr:1208C>T (human)RGD 
Cxcl15Mouseacute pyelonephritis susceptibilityISOCXCL8 (Homo sapiens)DNA:SNP:promoter:g.-251T>A (rs4073) (human)RGD 
Cxcr2Ratacute pyelonephritis susceptibilityISOCXCR2 (Homo sapiens)DNA:polymorphism: :1208C>T (human)RGD 
Cxcr2Mouseacute pyelonephritis susceptibilityISOCXCR2 (Homo sapiens)DNA:polymorphism:3' utr:1208C>T (human)RGD 
CXCR1Humanpyelonephritis  IAGP DNA:SNP: :2608G>C (human)RGD 
Cxcr1Ratpyelonephritis  ISOCXCR1 (Homo sapiens)DNA:SNP: :2608G>C (human)RGD 
Cxcr1Mousepyelonephritis  ISOCXCR1 (Homo sapiens)DNA:SNP: :2608G>C (human)RGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CXCL8HumanBacteriuria susceptibilityIAGP DNA:SNP:promoter:g.-251T>A (rs4073)RGD 
CXCR2HumanBacteriuria susceptibilityIAGP DNA:polymorphism:3' utr:1208C>TRGD 
CXCL8HumanElevated circulating C-reactive protein concentration susceptibilityIAGP DNA:SNP:promoter:g.-251T>A (rs4073)RGD 
CXCR2HumanElevated circulating C-reactive protein concentration susceptibilityIAGP DNA:polymorphism:3' utr:1208C>TRGD 
CXCL8HumanElevated erythrocyte sedimentation rate susceptibilityIAGP DNA:SNP:promoter:g.-251T>A (rs4073)RGD 
CXCR2HumanElevated erythrocyte sedimentation rate susceptibilityIAGP DNA:polymorphism:3' utr:1208C>TRGD 
CXCL8HumanFever susceptibilityIAGP DNA:SNP:promoter:g.-251T>A (rs4073) RGD 
CXCR2HumanFever susceptibilityIAGP DNA:polymorphism:3' utr:1208C>TRGD 
CXCR2HumanPyuria susceptibilityIAGP DNA:polymorphism:3' utr:1208C>TRGD 
CXCL8HumanRecurrent pyelonephritis susceptibilityIAGP DNA:SNP:promoter:g.-251T>A (rs4073)RGD 
Objects Annotated

Genes (Rattus norvegicus)
Cxcr1  (C-X-C motif chemokine receptor 1)
Cxcr2  (C-X-C motif chemokine receptor 2)

Genes (Mus musculus)
Cxcl15  (C-X-C motif chemokine ligand 15)
Cxcr1  (C-X-C motif chemokine receptor 1)
Cxcr2  (C-X-C motif chemokine receptor 2)

Genes (Homo sapiens)
CXCL8  (C-X-C motif chemokine ligand 8)
CXCR1  (C-X-C motif chemokine receptor 1)
CXCR2  (C-X-C motif chemokine receptor 2)


Additional Information