Genotype and haplotype determination of IL1B (g.-511C> T and g.+3954C> T) and (IL1RN) in pediatric nephrolithiasis

Background: Nephrolithiasis is a multifactorial and polygenic disorder characterized by presence of stones in urinary tract. Interleukin1 (IL1) plays role in process of bone loss/hypercalciuria and is involved in formation of kidney stones. We investigated the association between IL1B promoter region and exon-5 (g.-511C > T and g.+3954C > T) polymorphism and variable number of tandem repeats in IL1 receptor antagonist, IL1RN (IVS2) with risk of stone formation in childhood nephrolithiasis in north Indian population. Methods: Control group of 60 healthy pediatric individuals (age range = 4-16 y) and 50 pediatric nephrolithiasis patients (age range = 2-14 y) were studied. Polymorphism was detected by PCR based restriction analysis. Haplotypes for IL1B and IL1RN were constructed using Arlequin v2.0 software. Results: Distribution of IL1RN gene polymorphism demonstrated significant difference (p = 0.023). Pediatric patients had significantly higher frequency of allele I in IL1RN (16% vs. 1.7%). The distribution of IL1B (g.-511C > T and g.+3954C > T) genotypes in patients and controls were similar (p = 0.263 and 0.694 respectively). There was a significant difference in haplotype frequencies between pediatric patients and control group (p < 0.05). Haplotype T-E1-I showed > 7-folds risk for trephrolithiasis (p = 0.033; OR = 7.07, 95% CI = 1.16-42.84). Conclusions: Significant association was observed for allele I* of IL1RN however, no association was observed for IL1B. Haplotype T-E1-I was significantly associated with higher risk of pediatric nephrolithiasis. These findings suggest that the IL1RN and haplotyping may be an influential marker for susceptibility to pediatric nephrolithiasis. (c) 2007 Elsevier B.V. All rights reserved.