RESUMEN
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.
Asunto(s)
Hipersensibilidad/genética , Interleucina-18/genética , Adulto , Estudios de Casos y Controles , República Checa , Análisis Mutacional de ADN , Femenino , Genes Letales , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Haplotipos , Humanos , Hipersensibilidad/inmunología , Hipersensibilidad/fisiopatología , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido SimpleRESUMEN
The study aimed to examine an association of three different single nucleotide polymorphisms (SNPs) of the IL-18 gene (-607 C/A, -137 G/C and -133 C/G) on chromosome 11q22 with allergic rhinitis (AR). Genotyping for the SNPs was performed using 539 patients with AR and 312 healthy control volunteers. Positivity to the skin prick test for the fungus Alternaria sp. in patients with AR, and IgE levels according to particular genotypes of selected SNPs, were also determined. There were no significant differences in the distribution of single IL-18 alleles or genotypes between controls and AR patients. However, frequencies of combined IL-18 genotypes arising from combinations of the three common polymorphisms (-607, -137 and -133) were significantly different between both groups (P = 0.009, P (corr) < 0.05, OR = 5.35, 95% CI: 1.9-15.2). There was a marginally significant association of the IL-18-607 variant with IgE levels (P = 0.05) in patients, but not in the case of the other SNPs. Patients allergic to Alternaria, but not those allergic to other antigens, showed a significant association with the IL-18-607 polymorphism (P = 0.0037, P (corr) < 0.05). Results suggest that IL-18 gene variants may be one of the factors participating in the pathogenesis of AR or its intermediary phenotypes.
Asunto(s)
Interleucina-18/genética , Polimorfismo de Nucleótido Simple/genética , Rinitis Alérgica Perenne/genética , Rinitis Alérgica Estacional/genética , Adulto , Estudios de Casos y Controles , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Inmunoglobulina E/sangre , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de RestricciónRESUMEN
Over ten genome-wide screens and many candidate genes studies were performed worldwide to elucidate genetic factors involved in the pathogenesis of bronchial asthma and other atopic diseases. Results from these studies were often discordant, which might have reflected complexity and heterogeneity of these multifactorial diseases. Among a variety of other loci, specific variants of the gene for IKAP (IKK complex-associated protein) were shown to be associated with bronchial asthma in children in a Japanese study. To test the possible role of SNPs in the coding region of the IKAP gene in atopic asthma or other atopic phenotypes in a highly homogenous Czech population, a case-control study including 373 patients and 309 healthy control subjects was performed. There were no significant differences in the genotype and allele distributions for any of five SNPs in the IKAP gene (T819C, G2295A, A2490G, T3214A and C3473T) between patients with atopic asthma or other atopic diseases and healthy controls. These results suggest that the polymorphisms in the coding region of the IKAP gene are unlikely to contribute to atopic disease risk in the Czech population.