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 nephrolithiasis (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.