Yatagai Yohei, Sakamoto Tohru, Masuko Hironori, Kaneko Yoshiko, Yamada Hideyasu, Iijima Hiroaki, Naito Takashi, Noguchi Emiko, Hirota Tomomitsu, Tamari Mayumi, Imoto Yoshimasa, Tokunaga Takahiro, Fujieda Shigeharu, Konno Satoshi, Nishimura Masaharu, Hizawa Nobuyuki
Department of Pulmonary Medicine, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
PLoS One. 2013 Dec 4;8(12):e80941. doi: 10.1371/journal.pone.0080941. eCollection 2013.
Most of the previously reported loci for total immunoglobulin E (IgE) levels are related to Th2 cell-dependent pathways. We undertook a genome-wide association study (GWAS) to identify genetic loci responsible for IgE regulation. A total of 479,940 single nucleotide polymorphisms (SNPs) were tested for association with total serum IgE levels in 1180 Japanese adults. Fine-mapping with SNP imputation demonstrated 6 candidate regions: the PYHIN1/IFI16, MHC classes I and II, LEMD2, GRAMD1B, and chr13∶60576338 regions. Replication of these candidate loci in each region was assessed in 2 independent Japanese cohorts (n = 1110 and 1364, respectively). SNP rs3130941 in the HLA-C region was consistently associated with total IgE levels in 3 independent populations, and the meta-analysis yielded genome-wide significance (P = 1.07×10(-10)). Using our GWAS results, we also assessed the reproducibility of previously reported gene associations with total IgE levels. Nine of 32 candidate genes identified by a literature search were associated with total IgE levels after correction for multiple testing. Our findings demonstrate that SNPs in the HLA-C region are strongly associated with total serum IgE levels in the Japanese population and that some of the previously reported genetic associations are replicated across ethnic groups.
先前报道的大多数与总免疫球蛋白E（IgE）水平相关的基因座都与Th2细胞依赖性途径有关。我们进行了一项全基因组关联研究（GWAS），以确定负责IgE调节的基因座。对1180名日本成年人的479,940个单核苷酸多态性（SNP）进行了与血清总IgE水平的关联性测试。通过SNP填充进行的精细定位显示了6个候选区域：PYHIN1/IFI16、I类和II类主要组织相容性复合体（MHC）、LEMD2、GRAMD1B和chr13∶60576338区域。在2个独立的日本队列（分别为n = 1110和1364）中评估了每个区域中这些候选基因座的重复性。HLA-C区域中的SNP rs3130941在3个独立人群中均与总IgE水平持续相关，荟萃分析产生了全基因组显著性（P = 1.07×10(-10)）。利用我们的GWAS结果，我们还评估了先前报道的与总IgE水平相关的基因关联性的可重复性。通过文献检索确定的32个候选基因中有9个在进行多重检验校正后与总IgE水平相关。我们的研究结果表明，HLA-C区域中的SNP与日本人群中的血清总IgE水平密切相关，并且一些先前报道的基因关联性在不同种族群体中得到了重复验证。
