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01 April 2010

Gene polymorphism of epidermal growth factor receptor and airway hyperresponsiveness in young allergic subjects without respiratory symptoms

Takahiro YoshikawaABCDEF, Hiroshi KanazawaADE, Junji TanakaCDE, Shigeo FujimotoB, Takushi YamamotoCE

Med Sci Monit 2010; 16(4): CR163-171 :: ID: 878497

Abstract

Background
Airway hyperresponsiveness (AHR) in young asymptomatic adults with atopy can be one of indicators of future symptomatic asthma. We aimed to investigate genetic association of epidermal growth factor receptor (EGFR) with the asymptomatic AHR.
Material and Method
We recruited one-hundred and eighty-nine allergic volunteers (mean age 19.5+/-1.4 y.o.) without history of respiratory symptoms, measured bronchial responsiveness to methacholine (0.3 to 10.0 mg/ml) and classified them into subjects with AHR and those without AHR according to a cutoff level of PC20 (8.0 mg/ml). Then, we genotyped 12 SNPs on EGFR gene, and estimate total imbalance of haplotypes frequencies within haplotype block between two groups.
Results
Seventy-two (38.1%) in 189 subjects exhibited 20% decrease in FEV1 from the baseline values by inhalation of methacholine 8.0mg/ml or less. Significant results were observed in the following haplotype block: rs 4947972 - rs 12718945 - rs 2072454 (block-1), rs 4947972 - rs 12718945 - rs 2227983 (block-2), or rs 4947972 - rs 12718945 - rs 2293347 (block-3). In each haplotype block, higher frequency of a haplotype, C-T-C (block-1), C-T-A (block-2) and C-T-A (block-3), was observed in subjects with AHR than in those without AHR (odds ratio and the corresponding P value; 3.289 and 0.00087 (block-1), 3.436 and 0.00055 (block-2), and 4.036 and 0.00181 (block-3), respectively). No significant differences were observed in serological parameters and pulmonary function between two subject groups.
Conclusions
Our results indicate that the EGFR gene polymorphism might be associated with presence of asymptomatic AHR in young allergic adults.

Keywords: Polymorphism, Genetic, Odds Ratio, Models, Genetic, Methacholine Chloride - pharmacology, Introns, Hypersensitivity - pathology, Haplotypes, Genotype, Gene Frequency, Bronchial Hyperreactivity - pathology, Alleles, Adult, Adolescent, Polymorphism, Single Nucleotide, Receptor, Epidermal Growth Factor - genetics

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750