Gushiken F C, Arnett F C, Ahn C, Thiagarajan P
University of Texas Health Science Center, Houston 77030, USA.
Arthritis Rheum. 1999 Jun;42(6):1189-93. doi: 10.1002/1529-0131(199906)42:6<1189::AID-ANR15>3.0.CO;2-8.
To determine the frequency of mutations in the phospholipid binding domain of beta2-glycoprotein I (beta2GPI) in patients with systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS), and to analyze the clinical correlations of such mutations with thromboembolic complications.
Exons 7 and 8 of beta2GPI, which encode for its fifth domain, were amplified by polymerase chain reaction, and the presence of mutations was determined by restriction digestion and single-strand conformation polymorphism analysis. A clinical correlation with these mutations and the presence of antiphospholipid antibodies (aPL), lupus anticoagulant (LAC), anti-beta2GPI antibody, and the development of thromboembolic complications was performed using chi-square and Fisher's exact tests.
From a total of 143 patients studied, we found that 5.6% were heterozygous for the mutation at exon 7 (codon 306), and 7.7% were heterozygous for the mutation at exon 8 (codon 316). No homozygous subjects were found for either mutation. No significant correlation between these mutations and the presence of aPL, LAC, or anti-beta2GPI antibodies was found. In patients with SLE (n = 95), 4 of 6 patients with exon 8 mutation had thrombosis, compared with 22 of 82 patients without the mutation (P = 0.043).
The prevalence of mutations in the fifth domain of beta2GPI in these patients with SLE and/or APS were similar to those previously reported for the general population. Heterozygosity for either mutation does not influence the incidence of aPL, but in patients with SLE, the mutation at exon 8 may predispose to thrombosis as an independent factor.
确定系统性红斑狼疮（SLE）和/或抗磷脂综合征（APS）患者β2糖蛋白I（β2GPI）磷脂结合结构域的突变频率，并分析此类突变与血栓栓塞并发症的临床相关性。
通过聚合酶链反应扩增编码β2GPI第五结构域的第7和第8外显子，并通过限制性酶切和单链构象多态性分析确定突变的存在。使用卡方检验和Fisher精确检验对这些突变与抗磷脂抗体（aPL）、狼疮抗凝物（LAC）、抗β2GPI抗体的存在以及血栓栓塞并发症的发生进行临床相关性分析。
在总共研究的143例患者中，我们发现5.6%的患者第7外显子（密码子306）突变呈杂合状态，7.7%的患者第8外显子（密码子316）突变呈杂合状态。两种突变均未发现纯合子个体。未发现这些突变与aPL、LAC或抗β2GPI抗体的存在之间存在显著相关性。在SLE患者（n = 95）中，6例第8外显子突变患者中有4例发生血栓形成，而82例无该突变的患者中有22例发生血栓形成（P = 0.043）。
这些SLE和/或APS患者中β2GPI第五结构域的突变患病率与先前报道的一般人群相似。任一突变的杂合性不影响aPL的发生率，但在SLE患者中，第8外显子突变可能作为一个独立因素易导致血栓形成。
