Association of interleukin-1 beta gene and receptor antagonist polymorphisms with calcium oxalate urolithiasis

作者：Mittal Rama D^*; Bid Hemant K; Manchanda Parmeet K; Kapoor Rakesh

来源：Journal of Endourology, 2007, 21(12): 1565-1570.

DOI：10.1089/end.2007.0071

Background and Purpose: Genetic polymorphisms of the interleukin-1 beta (IL-1 beta) promoter region (-511) and exon 5 +3954 and a variable number of tandem repeats in the IL receptor antagonist (IL-IRA) gene have been proposed as markers for calcium oxalate urolithiasis. Because the prevalence of these polymorphisms could be influenced by racial variation/ethnicity, we explored the association of IL-1 gene-cluster polymorphisms with stone formation in a north India population.
Patients and Methods: The case-control study involved 150 stone-free control subjects (mean age 46.5 +/- 10.5 years) and 130 patients (mean age 40.0 +/- 11.5 years) with calcium oxalate urolithiasis. Biallelic polymorphisms of two loci, IL-1 beta (-511) and IL-1 beta (+3954), as well as the penta-allelic variable number of tandem repeats of IL-IRA, were genotyped by polymerase chain reaction-based restriction analysis. Haplotypes were constructed for the IL-1 gene cluster using SNP Analyzer software.
Results: We observed a significant association between stone disease and IL-1,6 -511 and IL-IRA polymorphisms (P < 0.001 and P = 0.039, respectively), whereas no association was observed for IL-1,6 +3954 (P = 0.408). The frequency of the TT (-511) and I/II (410/240; IL-IRA) genotypes was higher in patients than in control subjects (501130 v 16/150 and 551130 v 38/150, respectively), whereas the frequencies of the haplo-types were similar (P = 0.485). Significant linkage disequilibrium showed that three genes were strongly linked (P < 0.0001). Patients with a combination of high IL-1 beta (-511 and +3954) and low IL-IRA genotypes were at significantly higher risk for urolithiasis (P < 0.001; odds ratio = 5.448, 0.013, and 2.560, respectively).
Conclusion: Our study demonstrated a strong association of IL-IRA and IL-1,beta-511 and suggested that differences in them IL-1 gene cluster could be linked to the risk of urolithiasis. A combination of IL-1 beta and IL-1RA associations exhibiting gene-gene interaction further substantiates the finding of risk.

• 出版日期2007-12
• 单位河北医科大学