Borgmann S, Endisch G, Urban S, Sitter T, Fricke H
Department of Internal Medicine, Ludwig-Maximilians University of Munich, Ziemssenstrasse 1, Munich, D-80336, Germany.
Clin Immunol. 2001 Feb;98(2):244-8. doi: 10.1006/clim.2000.4962.
The frequency of carriers of the alpha1-antitrypsin (alpha1-AT) deficiency allele PIZ is increased in patients with Wegener's granulomatosis (WG). The polymorphic protease inhibitor (PI) gene is part of a cluster of serine protease inhibitor (serpin) genes (AACT; alpha1-antichymotrypsin, PCI; protein C inhibitor, CBG; corticosteroid binding globulin, PIL; PI-like pseudogene) at chromosome 14q32.1. In this study we investigated whether the serpin gene cluster contributes to the background of Wegener's granulomatosis. Therefore, phenotyping of alpha1-AT was performed and simple tandem repeat polymorphisms (STRP) in the genes for CBG, PI, and PCI as well as two STRP (D14S55 and D14S48) flanking the centromeric and one (D14S51) flanking the telomeric region of the gene cluster were examined in a population of 79 patients with WG and 128 unrelated healthy controls. In WG patients an increased frequency of the PIZ defective allele is demonstrated as well as a linkage disequilibrium between all members of this gene cluster plus the centromeric and telomeric STRP. These results indicate an involvement of the serpin genes in the pathogenesis of Wegener's granulomatosis and it is possible that other genes located in the vicinity of D14S55 or D14S51 contribute to the genetic background of the disease.
在韦格纳肉芽肿（WG）患者中，α1-抗胰蛋白酶（α1-AT）缺陷等位基因PIZ携带者的频率有所增加。多态性蛋白酶抑制剂（PI）基因是位于14号染色体q32.1区域的丝氨酸蛋白酶抑制剂（serpin）基因簇（AACT；α1-抗糜蛋白酶、PCI；蛋白C抑制剂、CBG；皮质类固醇结合球蛋白、PIL；PI样假基因）的一部分。在本研究中，我们调查了serpin基因簇是否与韦格纳肉芽肿的发病背景有关。因此，对α1-AT进行了表型分析，并在79例WG患者和128名无关健康对照人群中检测了CBG、PI和PCI基因中的简单串联重复多态性（STRP），以及基因簇着丝粒侧翼的两个STRP（D14S55和D14S48）和端粒侧翼的一个STRP（D14S51）。在WG患者中，PIZ缺陷等位基因的频率增加，并且该基因簇的所有成员加上着丝粒和端粒STRP之间存在连锁不平衡。这些结果表明serpin基因参与了韦格纳肉芽肿的发病机制，并且位于D14S55或D14S51附近的其他基因可能对该疾病的遗传背景有贡献。
