Haplotype analysis of the interleukin-18 gene in Czech patients with allergic disorders

Abstract

The interleukin-18 ( IL-18) gene on chromosome 11q22 has been suggested as a susceptibility factor for allergies. To test for a possible role of IL-18 polymorphisms in Czech population, case-control study including 958 subjects (633 allergic patients and 325 healthy controls) was performed. An allele-specific polymerase chain reaction was used to analyze variants at positions −607 C/A (rs1946518) and −137 G/C (rs187238) in the promoter region together with the polymerase chain reaction–restriction fragment length polymorphism method for the detection of polymorphism at position −140 C/G (previously −133 C/G, rs360721) in intron 1 of the IL-18 gene. The −1297 C/T (rs360719) polymorphism was genotyped by real-time–polymerase chain reaction, using a predevelopment TaqMan allele discrimination assay. There were no significant differences in distribution of alleles or genotypes in any of four single nucleotide polymorphisms in the IL-18 gene between controls and patients. However, subsequent analysis revealed a significant difference in haplotype frequencies between the allergic patients and healthy subjects ( p < 0.01). Haplotype formed by −1297 C/−607 A/−137 C/−140 C alleles occurred significantly more frequently in patients than controls (0.0433 vs 0.0129; p < 0.0003; p corr< 0.01, OR = 3.37; 95% CI = 1.59–7.14). In contrast, there was no relationship among the IL-18 variants and total serum IgE level. Our results indicate that promoter polymorphisms in the IL-18 gene act in interaction and could play a role in allergic disorders.