Large scale genotyping study for asthma in the Japanese population

To perform a large-scale genotyping study to identify asthma-susceptibility genes in the Japanese population.We performed a large-scale, three-stage association study on 288 atopic asthmatics and 1032 controls, by using multiplex PCR-Invader assay methods at 82,935 single nucleotide polymorphisms (SNPs) (1st stage). SNPs that were strongly associated with asthma were further genotyped in samples from asthmatic families (216 families, 762 members, 2nd stage), 541 independent patients, and 744 controls (3rd stage).SNPs located in the 5' region of PEX19 (rs2820421) were significantly associated with P < 0.05 through the 1st to the 3rd stage analyses; however, the P values did not reach statistically significant levels (combined, P = 3.8 × 10-5; statistically significant levels with Bonferroni correction, P = 6.57 × 10-7). SNPs on HPCAL1 (rs3771140) and on IL18R1 (rs3213733) were associated with asthma in the 1st and 2nd stage analyses, but the associations were not observed in the 3rd stage analysis.No association attained genome-wide significance, but several loci for possible association emerged. Future studies are required to validate these results for the prevention and treatment of asthma.Asthma is the most common chronic disorder in children, and asthma exacerbation is an important cause of childhood morbidity and hospitalization. Currently, approximately 300 million people worldwide have asthma, and this disease claims the lives of 180,000 people every year [1].Asthma and atopy are complex phenotypes that are influenced by both genetic and environmental factors. Twin studies have supported the role of a strong genetic contribution with a heritability of 0.71 [2], and asthma shows a familial risk higher than that of many common diseases such as stroke, epilepsy, and most types of cancer [3]. Atopy is characterized by increased levels of immunoglobulin E (IgE) against common environmental allergens, and is considered the strongest predisposing factor for asthma. M