No association between interleukin‐18 gene polymorphisms and haplotypes in Dutch sarcoidosis patients

Abstract

Previously, an association between susceptibility to sarcoidosis and a polymorphism in the interleukin (IL-18) gene (IL-18 -607A/C) has been reported in Japanese. The aim of the present study was to validate this association in a clinically well-characterized population of Dutch Caucasians. Three other polymorphisms at positions -656, -137, and 1248 were included in order to extend the mapping of the IL-18 gene and to enable the construction of haplotypes. Polymorphisms were determined using sequence-specific primers (SSPs) and polymerase chain reaction (PCR). A total of 236 individuals was studied (133 patients and 103 controls). No significant differences were observed in the distribution of the -607 and the other polymorphisms between Dutch sarcoidosis patients and controls. However, significant differences in IL-18 -607 genotype and allele frequency distributions were found between the Dutch and the Japanese. From the investigated IL-18-promoter polymorphisms, we were able to deduce four haplotypes. No differences were observed in haplotype frequencies between Dutch sarcoidosis patients and controls. In conclusion, IL-18 polymorphisms do not appear to influence the susceptibility to sarcoidosis in Dutch Caucasians. Important differences in allele frequencies were observed between Japanese and Dutch sarcoidosis patients and controls.

IL18 and IL18R1 polymorphisms, lung CT and fibrosis: a longitudinal study in coal miners

“…TAKADA et al [3] reported a significantly higher frequency of the IL18 -607C allele in 119 Japanese sarcoidosis patients compared with 130 controls, and no association was found for the IL18 G-137C SNP. The significant association was not replicated in a population of Dutch Caucasians, where 133 sarcoidosis patients were compared with 103 controls [4]. The inconsistency between studies may be due to differences in IL18 -607A and -137C allelic frequencies between populations, or in asthma onset or biological pathways during disease progression.…”

“…CT score was not normally distributed, but nonparametric Kruskal-Wallis and standard parametric tests (ANOVA and unpaired t-test) gave similar pvalues. Analyses were conducted considering subjects heterozygous and subjects homozygous for the variant allele, and variant allele carriers, as in previous studies [3][4][5][6][7]. IL18 haplotype analysis was then performed using a maximum likelihood method for haplotype-phenotype association as implemented in the Testing Haplotype Effects In Association Studies (THESIAS) program [20,21].…”

“…A role for IL-18 in pulmonary inflammation has been suggested by studies in rodent models, but its importance is not clearly understood. In epidemiological genetic studies, the IL18 C-607A single nucleotide polymorphism (SNP) was significantly associated with higher prevalence of sarcoidosis in Japanese subjects [3] but not in Dutch subjects [4]. The IL18 A105C SNP was significantly associated with asthma [5], the G-allele of the IL18 promoter variant (-137G/ C) was associated with an increased risk of atopic asthma in the Swiss Study on Air Pollution and Lung Disease in Adults (SAPALDIA) Cohort Study [6], and the IL18 G-656A, G-137C, T-133G, T113G and C127T SNPs were significantly associated with high immunoglobulin (Ig)E levels, specific sensitisation to common allergens and seasonal allergic rhinitis in 105 Caucasian families [7].…”

Genetics of Sarcoidosis: Candidate Genes and Genome Scans

“…BALF and serum IL-18 levels are increased in sarcoidosis (71). An association between IL-18607 (A/C) polymorphism and sarcoidosis has been reported and refuted in Japanese (72,73) and white subjects (74,75).…”

Association of interleukin‐18 gene polymorphism with asthma in Chinese patients

“…These studies indicate that some detailed mechanisms of asthma formation are still controversial. Recent experiments have demonstrated that the 105A/C polymorphism of the IL-18 gene may be associated with the pathogenesis of asthma (31), but associations of some gene with a disease reported in previous studies could not be observed in different populations (32,33). That is, the same SNP but with distinct genetic backgrounds could either increase or decrease the risk of disease susceptibility.…”