Indelicato Manuela, Chiarenza Valentina, Libra Massimo, Malaponte Grazia, Bevelacqua Valentina, Marchini Maurizio, McCubrey James A, Stivala Franca, Scorza Raffaella, Mazzarino Maria Clorinda
Department of Biomedical Sciences, University of Catania, Catania, Italy.
J Clin Lab Anal. 2006;20(5):173-6. doi: 10.1002/jcla.20128.
Systemic sclerosis (SSc) is an autoimmune disease characterized by skin and internal organs fibrosis due to an extracellular matrix (ECM) accumulation of type I collagen. The turnover of the ECM is dependent on the balance between matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs). The disruption of this balance is involved in SSc because higher serum TIMP-1 levels have been demonstrated in SSc patients than in controls. On this basis, we analyzed three polymorphisms: -19A>G, +261C>T, and +372T>C of the TIMP-1 gene in SSc patients (67 females, eight males) and controls (29 females, nine males). The C allele of the +372T>C single nucleotide polymorphism (SNP) was observed at a higher frequency in male patients than in healthy individuals (P=0.02), while no differences were observed in the female subjects. Our findings suggest that the +372T>C polymorphism of the TIMP-1 gene is associated with SSc in male individuals. No association with the clinical characteristics of SSc Italian patients and TIMP-1 gene polymorphisms was observed. Thus, the role of TIMP-1 gene in predisposition to SSc remains controversial.
系统性硬化症（SSc）是一种自身免疫性疾病，其特征是由于I型胶原蛋白在细胞外基质（ECM）中积聚导致皮肤和内脏器官纤维化。ECM的周转取决于基质金属蛋白酶（MMPs）和基质金属蛋白酶组织抑制剂（TIMPs）之间的平衡。这种平衡的破坏与SSc有关，因为已证明SSc患者的血清TIMP-1水平高于对照组。在此基础上，我们分析了SSc患者（67名女性，8名男性）和对照组（29名女性，9名男性）中TIMP-1基因的三种多态性：-19A>G、+261C>T和+372T>C。在男性患者中观察到+372T>C单核苷酸多态性（SNP）的C等位基因频率高于健康个体（P=0.02），而在女性受试者中未观察到差异。我们的研究结果表明，TIMP-1基因的+372T>C多态性与男性个体的SSc相关。未观察到TIMP-1基因多态性与意大利SSc患者临床特征之间的关联。因此，TIMP-1基因在SSc易感性中的作用仍存在争议。
