Yin Hong, Borghi Maria Orietta, Delgado-Vega Angélica M, Tincani Angela, Meroni Pier-Luigi, Alarcón-Riquelme Marta E
Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden.
Arthritis Rheum. 2009 Aug;60(8):2468-71. doi: 10.1002/art.24701.
Primary antiphospholipid syndrome (APS) is formally classified by the presence of antiphospholipid antibodies, recurrent thrombosis, and/or pregnancy morbidity in the absence of any underlying full-blown systemic autoimmune disease. However, systemic manifestations in patients with primary APS have been recently reported, as has the presence of serologic markers in common with systemic lupus erythematosus (SLE). In spite of similarities between the 2 diseases, only a minority of cases of primary APS evolve into full-blown SLE, even after a long followup period. The aim of this study was to investigate whether the analysis of SLE susceptibility genes may provide at least a partial explanation for such a discrepancy.
One hundred thirty-three patients with primary APS classified according to the Sydney criteria and 468 healthy control subjects from the same geographic area were recruited. We genotyped 3 single-nucleotide polymorphisms (SNPs) in IRF5 (rs2004640, rs2070197, and rs10954213), 4 SNPs in STAT4 (rs1467199, rs3821236, rs3024866, and rs7574865), 2 SNPs in BANK1 (rs10516487 and rs3733197), and 1 SNP in BLK (rs2736340).
STAT4 and BLK displayed a strong genetic association with primary APS (for rs7574865, odds ratio [OR] 2.19, P=5.17x10(-7); for rs2736340, OR 2.06, P=1.78x10(-6)), while a weak association with IRF5 and no association with BANK1 were observed.
The presence of a strong genetic association with only a few SLE susceptibility genes and the absence of a more complex gene association may contribute to the lack of cases of full-blown SLE developing in patients with primary APS, in spite of the clinical and serologic similarities between SLE and primary APS.
原发性抗磷脂综合征（APS）的正式分类依据是存在抗磷脂抗体、复发性血栓形成和/或妊娠并发症，且无任何潜在的全身性自身免疫性疾病。然而，近期有报道称原发性APS患者存在全身表现，以及与系统性红斑狼疮（SLE）共有的血清学标志物。尽管这两种疾病存在相似之处，但即使经过长时间随访，只有少数原发性APS病例会发展为典型的SLE。本研究的目的是调查对SLE易感基因的分析是否至少能部分解释这种差异。
招募了133例根据悉尼标准分类的原发性APS患者和来自同一地理区域的468名健康对照者。我们对IRF5基因中的3个单核苷酸多态性（SNP）（rs2004640、rs2070197和rs10954213）、STAT4基因中的4个SNP（rs1467199、rs3821236、rs3024866和rs7574865）、BANK1基因中的2个SNP（rs10516487和rs3733197）以及BLK基因中的1个SNP（rs2736340）进行基因分型。
STAT4和BLK与原发性APS显示出强烈的基因关联（对于rs7574865，比值比[OR]为2.19，P = 5.17×10⁻⁷；对于rs2736340，OR为2.06，P = 1.78×10⁻⁶），而观察到与IRF5的关联较弱，与BANK1无关联。
尽管SLE和原发性APS在临床和血清学上存在相似之处，但仅与少数SLE易感基因存在强烈的基因关联且不存在更复杂的基因关联，可能是原发性APS患者中典型SLE病例较少的原因。
