Asthma is a complex phenotype influenced by genetic and environmental factors. We conducted a genome-wide association study (GWAS) with 938 Japanese pediatric asthma patients and 2,376 controls. Single-nucleotide polymorphisms (SNPs) showing strong associations (P<1×10−8) in GWAS were further genotyped in an independent Japanese samples (818 cases and 1,032 controls) and in Korean samples (835 cases and 421 controls). SNP rs987870, located between HLA-DPA1 and HLA-DPB1, was consistently associated with pediatric asthma in 3 independent populations (P combined = 2.3×10−10, odds ratio [OR] = 1.40). HLA-DP allele analysis showed that DPA1*0201 and DPB1*0901, which were in strong linkage disequilibrium, were strongly associated with pediatric asthma (DPA1*0201: P = 5.5×10−10, OR = 1.52, and DPB1*0901: P = 2.0×10−7, OR = 1.49). Our findings show that genetic variants in the HLA-DP locus are associated with the risk of pediatric asthma in Asian populations.

The aim of the study was to clarify the relationship between current pet ownership, passive smoking, and allergic diseases among the Japanese children. From 1995 to 2001, we distributed the Japanese edition of the questionnaire of the American Thoracic Society and the Division of Lung Diseases (ATS-DLD) to survey allergic diseases among 35,552 6-yr-old children at primary school in the city of Himeji, Japan. We analyzed the data by multiple logistic regression and calculated adjusted odds ratios for environmental factors, including passive smoking and pet (dog and/or cat) ownership. There were no significant relationships between the prevalence of asthma and current pet ownership and passive smoking. However, current cat ownership was related to a significantly lower prevalence of atopic dermatitis [adjusted odds ratio (aOR) 0.79, 95% confidence interval (CI) 0.67-0.93], allergic rhinitis (aOR: 0.71, 95% CI 0.57-0.89) and Japanese cedar pollinosis (aOR 0.57, 95% CI 0.44-0.75). Strikingly, passive smoking was also related to a significantly lower prevalence of allergic rhinitis (aOR 0.83, 95% CI 0.77-0.89) and Japanese cedar pollinosis (aOR 0.81, 95% CI 0.74-0.88). Current cat ownership was associated with a lower prevalence of atopic dermatitis, allergic rhinitis, and Japanese cedar pollinosis. In addition, passive smoking was also associated with a lower prevalence of allergic rhinitis and Japanese cedar pollinosis.