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
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
acute pyelonephritis susceptibilityIAGP 7207860DNA:SNP:promoter:g.-251T>A (rs4073) (human)RGD 
acute pyelonephritis susceptibilityIAGP 7207860DNA:polymorphism:3' utr:1208C>T (human)RGD 
acute pyelonephritis susceptibilityISOCXCL8 (Homo sapiens)7207860DNA:SNP:promoter:g.-251T>A (rs4073) (human)RGD 
acute pyelonephritis susceptibilityISOCXCR2 (Homo sapiens)7207860DNA:polymorphism: :1208C>T (human)RGD 
acute pyelonephritis susceptibilityISOCXCR2 (Homo sapiens)7207860DNA:polymorphism:3' utr:1208C>T (human)RGD 
pyelonephritis  IAGP 7207860DNA:SNP: :2608G>C (human)RGD 
pyelonephritis  ISOCXCR1 (Homo sapiens)7207860; 7207860DNA:SNP: :2608G>C (human)RGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Bacteriuria susceptibilityIAGP 7207860DNA:SNP:promoter:g.-251T>A (rs4073)RGD 
Bacteriuria susceptibilityIAGP 7207860DNA:polymorphism:3' utr:1208C>TRGD 
Elevated circulating C-reactive protein concentration susceptibilityIAGP 7207860DNA:SNP:promoter:g.-251T>A (rs4073)RGD 
Elevated circulating C-reactive protein concentration susceptibilityIAGP 7207860DNA:polymorphism:3' utr:1208C>TRGD 
Elevated erythrocyte sedimentation rate susceptibilityIAGP 7207860DNA:SNP:promoter:g.-251T>A (rs4073)RGD 
Elevated erythrocyte sedimentation rate susceptibilityIAGP 7207860DNA:polymorphism:3' utr:1208C>TRGD 
Fever susceptibilityIAGP 7207860DNA:SNP:promoter:g.-251T>A (rs4073) RGD 
Fever susceptibilityIAGP 7207860DNA:polymorphism:3' utr:1208C>TRGD 
Pyuria susceptibilityIAGP 7207860DNA:polymorphism:3' utr:1208C>TRGD 
Recurrent pyelonephritis susceptibilityIAGP 7207860DNA: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