Interleukin-13 genetic polymorphisms in Singapore Chinese children correlate with long-term outcome of minimal-change disease.
BACKGROUND
Minimal-change nephrotic syndrome (MCNS) has been associated with atopy. As interleukin-13 (IL-13) has been implicated in the pathogenesis of MCNS, we postulated that IL-13 genetic polymorphisms could influence either susceptibility or clinical course of the disease.


METHODS
Seventy-two Singapore Chinese children with MCNS and 78 normal controls were screened for single nucleotide polymorphisms (SNPs) in the IL-13 gene by direct sequencing. Allele and genotype frequencies of these SNPs were determined and their relationship with different clinical courses was analysed.


RESULTS
Six SNPs were identified in the 5' promoter, exon 4 and 3' untranslated region (3'UTR). The three SNPs in the 3'UTR--4738 (G/A), 4793 (C/A) and 4926 (C/T)--were in tight linkage disequilibrium (Delta > or = 0.99). There was no difference in allele or genotype frequencies between MCNS children and normal controls. However, there was a significantly lower frequency of allele 4738G in those MCNS children who were still relapsing after 5 years of follow-up (G = 0.52), compared with those in complete remission (G = 0.72; P<0.05) and normal controls (G = 0.69; P<0.05). Haplotype analysis showed a significantly higher frequency of the GCC haplotype in controls and MCNS patients in complete remission (chi2 = 6.35; P<0.02), while the frequency of AAT haplotype was higher in those MCNS children still relapsing after 5 years of follow-up (chi2 = 5.38; P<0.02). Moreover, peripheral blood mononuclear cell IL-13 mRNA expression in patients with haplotype AAT was significantly higher than in those with haplotype GCC.


CONCLUSIONS
These results suggest that genetic polymorphisms in the 3'UTR of the IL-13 gene correlate with long-term outcome of MCNS, rather than disease susceptibility, in Singapore Chinese children.
Wei
Chang-Li
CL
Department of Pediatrics, National University of Singapore, 10 Lower Kent Ridge Crescent, 119074 Singapore.
Cheung
Wai
W
Heng
Chew-Kiat
CK
Arty
Novi
N
Chong
Samuel S
SS
Lee
Bee-Wah
BW
Puah
Ken-Lee
KL
Yap
Hui-Kim
HK
D002648:Child; D002675:Child, Preschool; D002681:China / Q000208:ethnology; D005260:Female; D006801:Humans; D007223:Infant; D018793:Interleukin-13 / Q000235:genetics*; D008297:Male; D009402:Nephrosis, Lipoid / Q000235:genetics*; D011110:Polymorphism, Genetic; D012846:Singapore; D013997:Time Factors
D018793:Interleukin-13