Laboratório de Imunomodulação e Novas Abordagens Terapêuticas (LINAT), Núcleo de Pesquisa em Inovação Terapêutica - Suely Galdino (NUPIT-SG), Universidade Federal de Pernambuco (UFPE), Recife, PE, Brazil.
Departmento de Oceanografia, Universidade Federal de Pernambuco, Recife, PE, Brazil.
Autoimmunity. 2021 Jun;54(4):187-194. doi: 10.1080/08916934.2021.1919881. Epub 2021 May 11.
Systemic sclerosis (SSc) is a rare complex disease characterized by vascular damage, autoimmunity, and extensive skin and internal organs fibrosis. Galectin-3 (Gal-3) is encoded by gene (Lectin, Galactoside-Binding, Soluble, 3; 14q22.3) and it has been reported to play a central role in self-tolerance, inflammation, and fibrosis.
To investigate associations among single nucleotide polymorphisms (SNPs) and serum levels Gal-3 and SSc susceptibility and their clinical features.
A case-control study with 88 patients and 151 matched controls was performed. variants were analyzed by the TaqMan real-time polymerase chain reaction (PCR) system whereas Gal-3 serum levels were measured by sandwich enzyme linked immunosorbent assay (ELISA). Associations among genotypes, clinical features, and Gal-3 levels were performed by univariable and multivariable analysis through statistical packages.
The rs4652 A/C genotype was more frequent in SSc patients than controls according to overdominant model [OR 1.89 (CI 95% 1.01 - 3.52); = .046]. Also, rs4652 C/C polymorphic genotype was associated with lower patient Gal-3 levels ( = .03) and control group ( = 0.005), as noted by generalized linear model (GLM). The rs1009977 G/T controls showed higher Gal-3 levels than wild-type and polymorphic genotypes ( = .03); however, in SSc patients, no difference was found. None of the SNPs or Gal-3 levels was associated with clinical manifestations in SSc patients. Considering only the SSc group, GLM analysis pointed rs4652 and rs2075601, pulmonary arterial hypertension (PAH), myopathy, and health assessment questionnaire (HAQ) and scleroderma health assessment questionnaire (SHAQ) as important predictors for Gal-3 levels.
The rs4652 A/C was more frequent in SSc patients and related to lower Gal-3 levels. These findings were corroborated through a GLM to estimate Gal-3 values. Also, by model equations, Gal-3 levels may be predicted by HAQ, SHAQ, PAH, myopathy, and rs4652 and rs2075601 factors. In these ways, we suggest that galectins may be promising biomarkers to identify susceptibility to SSc as well as to identify HAQ, SHAQ, PAH, and myopathy outcomes.
系统性硬化症（SSc）是一种罕见的复杂疾病，其特征为血管损伤、自身免疫和广泛的皮肤及内脏器官纤维化。半乳糖凝集素-3（Gal-3）由基因（Lectin，Galactoside-Binding，Soluble，3；14q22.3）编码，据报道其在自身耐受、炎症和纤维化中发挥中心作用。
研究单核苷酸多态性（SNP）与血清 Gal-3 水平及 SSc 易感性及其临床特征之间的关系。
采用病例对照研究，共纳入 88 例患者和 151 例匹配对照。采用 TaqMan 实时聚合酶链反应（PCR）系统分析 变体，夹心酶联免疫吸附试验（ELISA）测定 Gal-3 血清水平。采用单变量和多变量分析统计软件包分析基因型与临床特征和 Gal-3 水平之间的关系。
根据超显性模型，SSc 患者的 rs4652 A/C 基因型比对照组更为常见[比值比（OR）1.89（95%置信区间[CI]1.01-3.52）； = .046]。此外， rs4652 C/C 多态性基因型与患者和对照组 Gal-3 水平较低相关（ = .03），通过广义线性模型（GLM）得到证实。与野生型和多态性基因型相比， rs1009977 G/T 基因型的对照组 Gal-3 水平更高（ = .03）；然而，在 SSc 患者中未发现差异。在 SSc 患者中，未发现任何 SNP 或 Gal-3 水平与临床表现相关。仅考虑 SSc 组，GLM 分析指出 rs4652 和 rs2075601、肺动脉高压（PAH）、肌病和健康评估问卷（HAQ）和硬皮病健康评估问卷（SHAQ）是 Gal-3 水平的重要预测因子。
SSc 患者中 rs4652 A/C 更为常见，与 Gal-3 水平较低有关。通过 GLM 估计 Gal-3 值对这些发现进行了验证。此外，通过模型方程，HAQ、SHAQ、PAH、肌病和 rs4652 和 rs2075601 等因素可以预测 Gal-3 水平。通过这些方式，我们认为半乳糖凝集素可能是识别 SSc 易感性以及识别 HAQ、SHAQ、PAH 和肌病结局的有前途的生物标志物。
