The first genome-wide association study identifying new susceptibility loci for obstetric antiphospholipid syndrome
The first genome-wide association study identifying new susceptibility loci for obstetric antiphospholipid syndrome
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第一项全基因组关联研究确定了产科抗磷脂综合征的新易感位点
DOI：
10.1038/jhg.2017.46
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发表时间：
2017
影响因子：
3.5
通讯作者：
Ozaki Ya
中科院分区：
文献类型：
--
作者：
Sugiura-Ogasawara Mayumi;Omae Yosuke;Kawashima Minae;Toyo-Oka Licht;Khor Seik-Soon;Sawai Hiromi;Horita Tetsuya;Atsumi Tatsuya;Murashima Atsuko;Fujita Daisuke;Fujita Tomio;Morimoto Shinji;Morishita Eriko;Katsuragi Shinji;Kitaori Tamao;Katano Kinue;Ozaki Ya
抗磷脂综合征（APS）是反复妊娠丢失的最重要的可治疗原因。在接受既定抗凝治疗的APS患者中，活产率仅限于70-80%。狼疮抗凝剂（LA），而不是抗心磷脂抗体（ACL），被发现预测不良妊娠结局。最近的APS全基因组关联研究（GWAS）集中于ACL，表明可能涉及几种分子。这是第一个针对产科APS的GWAS，重点是洛杉矶。一个GWAS进行比较115例日本产科APS患者，诊断标准的国际会议上APS，419名健康人。共比较了426344个单核苷酸多态性（SNP）的等位基因或基因型频率。还对GWAS检测到的候选区域进行了插补分析。根据Bonferroni校正后的隐性模型，TSHR 3′-UTR上的一个SNP（rs 2288493）在整个实验范围内显示出显著的APS关联（P= 7.85 E-08，OR= 6.18）。另一个位于C1 D附近的SNP（rs79154414）在应用SNP插补后的等位基因模型下显示出全基因组显著的APS关联（P= 4.84 E-08，OR= 6.20）。我们的研究结果表明，TSHR和C1 D基因的特定基因型可能是产科APS的危险因素。
Antiphospholipid syndrome (APS) is the most important treatable cause of recurrent pregnancy loss. The live birth rate is limited to only 70–80% in patients with APS undergoing established anticoagulant therapy. Lupus anticoagulant (LA), but not anticardiolipin antibody (aCL), was found to predict adverse pregnancy outcome. Recent genome-wide association studies (GWAS) of APS focusing on aCL have shown that several molecules may be involved. This is the first GWAS for obstetric APS focusing on LA. A GWAS was performed to compare 115 Japanese patients with obstetric APS, diagnosed according to criteria of the International Congress on APS, and 419 healthy individuals. Allele or genotype frequencies were compared in a total of 426 344 single-nucleotide polymorphisms (SNPs). Imputation analyses were also performed for the candidate regions detected by the GWAS. One SNP (rs2288493) located on the 3′-UTR of TSHR showed an experiment-wide significant APS association (P= 7.85 E-08, OR= 6.18) under a recessive model after Bonferroni correction considering the number of analyzed SNPs. Another SNP (rs79154414) located around the C1D showed a genome-wide significant APS association (P= 4.84 E-08, OR= 6.20) under an allelic model after applying the SNP imputation. Our findings demonstrate that a specific genotype of TSHR and C1D genes can be a risk factor for obstetric APS.