| Summary: | <p>Abstract</p> <p>Background</p> <p>Asthma is a complex phenotype that is influenced by both genetic and environmental factors. Genome-wide linkage and association studies have been performed to identify susceptibility genes for asthma. These studies identified new genes and pathways implicated in this disease, many of which were previously unknown.</p> <p>Objective</p> <p>To perform a large-scale genotyping study to identify asthma-susceptibility genes in the Japanese population.</p> <p>Methods</p> <p>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) (1<sup>st </sup>stage). SNPs that were strongly associated with asthma were further genotyped in samples from asthmatic families (216 families, 762 members, 2<sup>nd </sup>stage), 541 independent patients, and 744 controls (3<sup>rd </sup>stage).</p> <p>Results</p> <p>SNPs located in the 5' region of <it>PEX19 </it>(rs2820421) were significantly associated with <it>P </it>< 0.05 through the 1<sup>st </sup>to the 3<sup>rd </sup>stage analyses; however, the <it>P </it>values did not reach statistically significant levels (combined, <it>P </it>= 3.8 × 10<sup>-5</sup>; statistically significant levels with Bonferroni correction, <it>P </it>= 6.57 × 10<sup>-7</sup>). SNPs on <it>HPCAL1 </it>(rs3771140) and on <it>IL18R1 </it>(rs3213733) were associated with asthma in the 1<sup>st </sup>and 2<sup>nd </sup>stage analyses, but the associations were not observed in the 3<sup>rd </sup>stage analysis.</p> <p>Conclusion</p> <p>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.</p>
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