Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, , Seoul, Korea.
Ann Rheum Dis. 2014 Jun;73(6):1240-5. doi: 10.1136/annrheumdis-2012-202675. Epub 2013 Jun 5.
To identify novel genetic candidates for systemic lupus erythematosus (SLE) in the Korean population, and to validate the risk loci for SLE identified in previous genome-wide association studies (GWAS).
We performed a GWAS in 400 Korean female SLE patients and 445 controls. Selected single-nucleotide polymorphisms (SNP) were then replicated in an independent cohort of 385 SLE patients and 583 controls (replication cohort 1), and in a further 811 SLE patients and 1502 controls (replication cohort 2).
In the GWAS phase, rs9275428 located near HLA-DQB1 showed the strongest association with SLE (OR 0.50, false discovery rate (FDR) p=3.07×10(-6)). Although no loci reached genome-wide significance outside major histocompatibility complex (MHC), C8orf13-BLK, STAT4, CSMD1, DIAPH3, GLDC and TNFSF4 showed FDR p < 0.05. Our results suggest that STAT4, BLK, IRF5, PTTG1-miR-146a, UBE2L3 and TNFAIP3 are shared susceptibility loci among Caucasians and Asians, while ETS1, IKZF1, SLC15A4 are likely to be Asian-specific loci. In a combined analysis of 1596 SLE patients and 2540 controls for selected 22 candidate SNP, STAT4 and BLK as positive controls showed a strong association with SLE (FDR p=9.85×10(-13) and 2.28×10(-8), respectively). Of these, 16 candidates (PEX5L, TRAJ50, MYO18B, SOS1, ARHGAP26, SMURF1, CADPS, HAND1, FAM78B, DIAPH3, TBL1XR1, CSMD1, ZBTB20, C3orf21, HIPK1 and AP001042.1) showed only nominal significance (7.05×10(-4)≤FDR p≤4.38×10(-2)).
There are similarities and differences in genetic susceptibility for SLE between Caucasian and Asian ethnic groups. Although 16 putative novel loci for SLE have been suggested in the Korean population, further research on a larger sample is required to discriminate truth from error.
在韩国人群中鉴定系统性红斑狼疮（SLE）的新遗传候选基因，并验证先前全基因组关联研究（GWAS）中鉴定的 SLE 风险基因座。
我们对 400 名韩国女性 SLE 患者和 445 名对照进行了 GWAS。然后在一个独立的队列中（验证队列 1）对选定的单核苷酸多态性（SNP）进行了复制，该队列包括 385 名 SLE 患者和 583 名对照，在另一个队列（验证队列 2）中包括 811 名 SLE 患者和 1502 名对照。
在 GWAS 阶段，位于 HLA-DQB1 附近的 rs9275428 与 SLE 相关性最强（OR 0.50，假发现率（FDR）p=3.07×10(-6)）。尽管除了主要组织相容性复合体（MHC）之外，没有任何基因座达到全基因组显著性，但 C8orf13-BLK、STAT4、CSMD1、DIAPH3、GLDC 和 TNFSF4 的 FDR p<0.05。我们的结果表明，STAT4、BLK、IRF5、PTTG1-miR-146a、UBE2L3 和 TNFAIP3 是白种人和亚洲人之间共同的易感基因座，而 ETS1、IKZF1、SLC15A4 可能是亚洲特有的基因座。在对 22 个候选 SNP 进行的 1596 名 SLE 患者和 2540 名对照的综合分析中，STAT4 和 BLK 作为阳性对照与 SLE 有很强的相关性（FDR p=9.85×10(-13)和 2.28×10(-8)）。其中，16 个候选基因（PEX5L、TRAJ50、MYO18B、SOS1、ARHGAP26、SMURF1、CADPS、HAND1、FAM78B、DIAPH3、TBL1XR1、CSMD1、ZBTB20、C3orf21、HIPK1 和 AP001042.1）仅显示出名义显著性（7.05×10(-4)≤FDR p≤4.38×10(-2)）。
白种人和亚洲人群的 SLE 遗传易感性既有相似之处，也有不同之处。尽管在韩国人群中提出了 16 个 SLE 的新候选基因座，但需要对更大的样本进行进一步研究，以区分真伪。
