Abstract

Introduction

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 LGALS3 (Lectin, Galactoside-Binding, Soluble, 3; 14q22.3) and it has been reported to play a central role in self-tolerance, inflammation, and fibrosis.

Objective

To investigate associations among LGALS3 single nucleotide polymorphisms (SNPs) and serum levels Gal-3 and SSc susceptibility and their clinical features.

Methods

A case-control study with 88 patients and 151 matched controls was performed. LGALS3 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.

Results

The LGALS3 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); p = .046]. Also, LGALS3 rs4652 C/C polymorphic genotype was associated with lower patient Gal-3 levels (p = .03) and control group (p = 0.005), as noted by generalized linear model (GLM). The LGALS3 rs1009977 G/T controls showed higher Gal-3 levels than wild-type and polymorphic genotypes (p = .03); however, in SSc patients, no difference was found. None of the LGALS3 SNPs or Gal-3 levels was associated with clinical manifestations in SSc patients. Considering only the SSc group, GLM analysis pointed LGALS3 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.

Conclusion

The LGALS3 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 LGALS3 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.

中文翻译：

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LGALS3 的遗传变异与系统性硬化症患者较低的半乳糖凝集素 3 血清水平和临床结果有关：病例对照研究

摘要

介绍

系统性硬化症 (SSc) 是一种罕见的复杂疾病，其特征是血管损伤、自身免疫以及广泛的皮肤和内脏器官纤维化。Galectin-3 (Gal-3) 由基因LGALS3 (Lectin, Galactoside-Binding, Soluble, 3; 14q22.3) 编码，据报道它在自我耐受、炎症和纤维化中发挥核心作用。

客观的

研究LGALS3单核苷酸多态性 (SNP) 与血清水平 Gal-3 和 SSc 易感性及其临床特征之间的关联。

方法

对 88 名患者和 151 名匹配对照进行了病例对照研究。通过 TaqMan 实时聚合酶链反应 (PCR) 系统分析LGALS3变体，而通过夹心酶联免疫吸附测定 (ELISA) 测量 Gal-3 血清水平。基因型、临床特征和 Gal-3 水平之间的关联通过统计包的单变量和多变量分析进行。

结果

根据过度显性模型，SSc 患者的LGALS3 rs4652 A/C 基因型比对照组更常见 [OR 1.89 (CI 95% 1.01 - 3.52)；p  = .046]。此外，正如广义线性模型 (GLM) 所指出的， LGALS3 rs4652 C/C 多态性基因型与较低的患者 Gal-3 水平 ( p  = .03) 和对照组 ( p  = 0.005) 相关。LGALS3 rs1009977 G/T 对照显示出比野生型和多态基因型更高的 Gal-3 水平 ( p  = .03)；然而，在 SSc 患者中，没有发现差异。没有一个LGALS3SNP 或 Gal-3 水平与 SSc 患者的临床表现相关。仅考虑 SSc 组，GLM 分析指出LGALS3 rs4652 和 rs2075601、肺动脉高压 (PAH)、肌病、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。

结论

LGALS3 rs4652 A/C 在 SSc 患者中更常见，并且与较低的 Gal-3 水平有关。这些发现通过 GLM 得到证实，以估计 Gal-3 值。此外，通过模型方程，Gal-3 水平可以通过 HAQ、SHAQ、PAH、肌病和LGALS3 rs4652 和 rs2075601 因子预测。通过这些方式，我们认为半乳凝素可能是有希望的生物标志物，可用于识别 SSc 易感性以及识别 HAQ、SHAQ、PAH 和肌病结果。