J Korean Med Sci.  2012 Apr;27(4):382-387. 10.3346/jkms.2012.27.4.382.

Effect of Interleukin-18 Gene Polymorphisms on Sensitization to Wheat Flour in Bakery Workers

• Kim SH
• Hur GY
• Jin HJ
• Choi H
• Park HS

• KMID: 2157898
• DOI: http://doi.org/10.3346/jkms.2012.27.4.382

Abstract

Lower respiratory symptoms in bakery workers may be induced by wheat flour and endotoxins. We hypothesized that endotoxins from wheat flour may stimulate innate immunity and that interleukin-18 (IL-18) gene polymorphisms may affect their regulatory role in innate immune responses to endotoxins. To investigate the genetic contribution of IL-18 to sensitization to wheat flour, we performed a genetic association study of IL-18 in Korean bakery workers. A total of 373 bakery workers undertook a questionnaire regarding work-related symptoms. Skin prick tests with common and occupational allergens were performed and specific antibodies to wheat flour were measured by ELISA. Three polymorphisms of the IL-18 gene (-607A/C, -137G/C, 8674C/G) were genotyped, and the functional effects of the polymorphisms were analyzed using the luciferase reporter assay. Genotypes of -137G/C (GC or CC) and haplotype ht3 [ACC] showed a significant association with the rate of sensitization to wheat flour. Luciferase activity assay indicated ht3 [AC] as a low transcript haplotype. In conclusion, the regulatory role of IL-18 in lipopolysaccharide-induced responses in bakery workers may be affected by this polymorphism, thus contributing to the development of sensitization to wheat flour and work-related respiratory symptoms.

Keyword

Interleukin-18; Genes; Polymorphism; Sensitization; Wheat Flour

MeSH Terms

Adult
Alleles
Allergens/immunology
Antibodies/analysis/immunology
Female
Genes, Reporter
Genotype
Haplotypes
Humans
Interleukin-18/*genetics
Male
Middle Aged
Occupational Diseases/*genetics/immunology
*Polymorphism, Single Nucleotide
Questionnaires
Respiratory Hypersensitivity/*genetics/immunology
Skin Tests
Triticum/*immunology

Figure

• 

  Fig. 1 Effects of promoter polymorphisms on transcription activity of the human IL-18 gene. (A) Promoter activity in a human alveolar basal epithelial cell line (A549). (B) Promoter activity in a human bronchial epithelial cell line (BEAS2B). Relative luciferase activity is represented as the ratio of activity to luciferase activity in cells transfected with the empty control vector pGL3-Basic. The luciferase activity assay was performed in three independent experiments (n = 9). Values represent the mean ± SD of nine data points in each group. Statistical differences were evaluated using an ANOVA.

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