A dysfunctional allele of the mannose binding protein gene associates with systemic lupus erythematosus in a Spanish population.
A dysfunctional allele of the mannose binding protein gene associates with systemic lupus erythematosus in a Spanish population.
复制标题
甘露糖结合蛋白基因的功能失调等位基因与西班牙人群的系统性红斑狼疮有关。
作者：
E. Davies;L. Teh;J. Ordi‐Ros;Neil Snowden;M. Hillarby;A. H. Hajeer;Rachelle Donn;P. Perez;M. Vilardell‐Tarrés;W. Ollier
目标
确定西班牙系统性红斑狼疮 (SLE) 患者功能失调的甘露糖结合蛋白 (MBP) 状态，并确定 MBP 和补体 C4 无效等位基因是否以附加方式增加 SLE 易感性。
方法
MBP 等位基因的频率（以外显子 1 密码子 54 和密码子 57 的多态性为特征）通过扩增难治性突变系统聚合酶链反应测定了 50 名西班牙 SLE 患者和 49 名匹配对照者。使用 Ban I 限制酶消化方法确认密码子 54 突变的突变基因型。通过对神经氨酸酶/羧肽酶 B 消化的血浆样品进行琼脂糖凝胶电泳，然后进行免疫固定和染色，实现补体 C4 同种异型分型。
结果
52% 的 SLE 患者和 31% 的对照者中至少存在一种功能失调的 MBP 等位基因，无法激活补体（OR = 2.4，95% CI 1.1-5.6）。 61% 的患者和 43% 的对照者存在补体 C4 无效等位基因（C4A 或 C4B）（OR = 2.1，95% CI 0.9-4.9）。 41% 的患者和 16% 的对照者存在功能失调的 MBP 等位基因和 C4 无效等位基因（OR = 3.2，95% CI 1.2-8.1）。
结论
功能失调的 MBP 等位基因的存在是西班牙人群患 SLE 的一个危险因素，并且可能以与 C4 无效等位基因相加的方式影响易感性。
OBJECTIVE
To determine dysfunctional mannose binding protein (MBP) status of Spanish patients with systemic lupus erythematosus (SLE) and to determine whether MBP and complement C4 null alleles contribute in an additive way to SLE susceptibility.
METHODS
The frequencies of MBP alleles (characterized by polymorphisms at codon 54 and codon 57 of exon 1) were determined by the amplification refractory mutation system-polymerase chain reaction in 50 Spanish patients with SLE and 49 matched controls. Mutant genotypes for the codon 54 mutation were confirmed using a Ban I restriction enzyme digest method. Complement C4 allotyping was achieved by agarose gel electrophoresis of neuraminidase/carboxypeptidase B digested plasma samples followed by immunofixation and staining.
RESULTS
At least one dysfunctional MBP allele, unable to activate complement, was present in 52% of patients with SLE and in 31% of controls (OR = 2.4, 95% CI 1.1-5.6). Complement C4 null alleles (either C4A or C4B) were present in 61% of patients and 43% of controls (OR = 2.1, 95% CI 0.9-4.9). A dysfunctional MBP allele and C4 null allele were present in 41% of patients and 16% of controls (OR = 3.2, 95% CI 1.2-8.1).
CONCLUSION
The presence of a dysfunctional MBP allele is a risk factor for developing SLE in this Spanish population and may affect susceptibility in an additive way with C4 null alleles.