Universidade de São Paulo, Ribeirão Preto-SP, Brazil.
Arch Dermatol Res. 2010 Oct;302(8):583-91. doi: 10.1007/s00403-010-1032-9. Epub 2010 Feb 7.
Antiphospholipid antibodies, such as anti-beta2-glycoprotein I (beta2GPI), are present in multibacillary leprosy (MB) patients; however, MB patients do not usually present with antiphospholipid antibody syndrome (APS), which is characterized by thromboembolic phenomena (TEP). Rare cases of TEP occur in leprosy patients, but the physiopathology of this condition remains unclear. In this case-control study, we examined whether single-nucleotide polymorphisms (SNPs) of the beta2GPI gene contributed to the risk of leprosy and APS co-morbidity. SNPs Ser88Asn, Leu247Val, Cys306Gly and Trp316Ser were identified in 113 Brazilian leprosy patients. Additionally, anti-beta2GPI antibodies and plasma concentrations of beta2GPI were quantified. The Ser88Asn, Cys306Gly and Trp316Ser SNPs were not risk factors for APS in leprosy. A higher frequency of Val/Val homozygosity was observed in leprosy patients compared to controls (36 vs. 5%; P < 0.001). Forty-two percent of MB and 17% of paucibacillary leprosy patients were positive for anti-beta2GPI IgM (P = 0.014). There was no correlation between SNP Ser88Asn or Cys306Gly and anti-beta2GPI antibody levels. In MB patients with positive anti-beta2GPI IgM, the frequency of Val/Val homozygosity was higher than in controls (32 vs. 15%; P = 0.042). The frequency of the mutant allele Ser316 was higher in MB patients with positive rather than negative anti-beta2GPI IgM levels (6 vs. 0%; P = 0.040) and was greater than in the control group (6 vs. 1%; P = 0.034). The studied polymorphisms did not influence the plasma concentrations of beta2GPI. These results suggest that Leu247Val and Trp316Ser SNPs may represent genetic risk factors for anti-beta2GPI antibody production in MB patients.
抗磷脂抗体，如抗β2-糖蛋白 I（β2GPI），存在于多菌型麻风病（MB）患者中；然而，MB 患者通常不出现抗磷脂抗体综合征（APS），其特征为血栓栓塞现象（TEP）。罕见的 TEP 发生在麻风病患者中，但该病症的病理生理学仍不清楚。在这项病例对照研究中，我们研究了β2GPI 基因的单核苷酸多态性（SNPs）是否导致麻风病和 APS 合并症的风险。在 113 名巴西麻风病患者中鉴定出了β2GPI 基因的 Ser88Asn、Leu247Val、Cys306Gly 和 Trp316Ser 等 SNPs。此外，还定量了抗β2GPI 抗体和β2GPI 血浆浓度。Ser88Asn、Cys306Gly 和 Trp316Ser SNPs 不是麻风病中 APS 的危险因素。与对照组相比，麻风病患者中观察到更高频率的 Val/Val 纯合性（36%对 5%；P < 0.001）。42%的 MB 和 17%的少菌型麻风病患者抗β2GPI IgM 阳性（P = 0.014）。SNP Ser88Asn 或 Cys306Gly 与抗β2GPI 抗体水平之间没有相关性。在抗β2GPI IgM 阳性的 MB 患者中，Val/Val 纯合性的频率高于对照组（32%对 15%；P = 0.042）。与抗β2GPI IgM 水平阴性的 MB 患者相比，携带突变等位基因 Ser316 的患者频率更高（6%对 0%；P = 0.040），且高于对照组（6%对 1%；P = 0.034）。所研究的多态性并未影响β2GPI 的血浆浓度。这些结果表明，Leu247Val 和 Trp316Ser SNPs 可能是 MB 患者抗β2GPI 抗体产生的遗传危险因素。
