INVITED EDITORIAL
研究了CAV1基因单核苷酸多态性与系统性硬化症（SSc）的关联，发现rs959173 C等位基因具有保护作用，且与CAV1蛋白表达增加相关，为SSc易感基因提供了新证据。
<h3>Objective</h3> Caveolin-1 (CAV1) is an inhibitor of tissue fibrosis and has been implicated in the pathogenesis of systemic sclerosis (SSc). The aim of the study was to analyse the possible association of <i>CAV1</i> gene single nucleotide polymorphisms (SNP) with SSc. <h3>Methods</h3> A total population of 3974 individuals (1355 SSc patients, 2619 controls) was studied. Genotype data for 23 SNP spanning the <i>CAV1–CAV2</i> gene locus were obtained from a genome-wide scan conducted in a French population (564 SSc patients, 1776 controls). Three <i>CAV1</i> SNP (rs926198, rs959173, rs9920) displaying the most significant associations with SSc and/or clinical phenotypes were then genotyped in an Italian population (791 SSc patients, 843 controls). CAV1 protein expression in skin biopsies was investigated by immunohistochemistry and western blotting. <h3>Results</h3> In the French population, the <i>CAV1</i> rs959173 C minor allele showed a significant protective association with susceptibility to SSc (OR 0.71, 95% CI 0.59 to 0.86, p<sub>adjusted</sub>=0.009), and with the subset of patients with limited cutaneous SSc (OR 0.71, 95% CI 0.56 to 0.89, p<sub>adjusted</sub>=0.018). The association was replicated in the Italian population and strengthened in the combined populations through Cochran–Mantel–Haenszel meta-analysis (SSc: pooled OR 0.81, 95% CI 0.71 to 0.92, p=0.0018; limited cutaneous SSc: pooled OR 0.80, 95% CI 0.69 to 0.93, p=0.0053). Genotype/protein expression correlations revealed that the rs959173 C protective allele was associated with increased <i>CAV1</i> protein expression. <h3>Conclusions</h3> These results add <i>CAV1</i> to the list of SSc susceptibility genes and provide further evidence for the contribution of this pathway in the fibrotic process that characterises SSc pathogenesis.