日本人群的大规模哮喘基因分型研究
2009/05/22
背景：哮喘具有较为复杂的基因分型，受到基因和环境因素的双重影响。应用全基因组连锁分析和关联分析来筛选哮喘的易感基因，分析过程中发现了很多与哮喘有关的新基因，其中大部分以前未知。
目的：在日本人群中进行大规模的基因分型研究，筛选哮喘易感基因。
方法：采用多重PCR侵染检测法，在288名特应性哮喘患者和1032名对照人群中，进行大规模的、三阶段的基因关联分析。第一阶段共分析82935个单核苷酸多态性（SNPs）。第二阶段对来源于哮喘家庭（216个家庭，762名成员）的样本中与哮喘密切相关的SNPs进一步分型。第三阶段对来源于541名独立患者和744名对照人群的样本中与哮喘密切相关的SNPs进一步分型。
结果：通过1～3阶段研究，发现与哮喘密切相关的SNPs主要位于PEX19（rs2820421）的5’区（P < 0.05）。但p值未达到统计学差异水平（联合P值为3.8 x 10-5；进行Bonferroni校正后有统计学差异：p= 6.57 x 10-7）。第1和2阶段研究显示位于HPCAL1 (rs3771140) 和IL18R1 (rs3213733)的SNPs与哮喘相关，但该相关性未在第3阶段观察到。
结论：虽然未获得全基因组的相关性，但发现某些位点可能与哮喘有关。需要进一步的研究来证实上述结果，以便对哮喘进行更好的预防和治疗。
（林江涛 审校）
Imada Y, et al. BMC Res Notes. 2009 Mar 31;2(1):54. [Epub ahead of print]
Large scale genotyping study for asthma in the Japanese population.
BACKGROUND: 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.
OBJECTIVE: To perform a large-scale genotyping study to identify asthma-susceptibility genes in the Japanese population.
METHODS: 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).
RESULTS: 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 x 10-5; statistically significant levels with Bonferroni correction, P = 6.57 x 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.
CONCLUSION: 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.
