Genetic variants in <i>LGALS3</i> are related to lower galectin-3 serum levels and clinical outcomes in systemic sclerosis patients: A case-control study
Creators: name: Cunha, Eudes Gustavo Constantino
name: De Lima, Camilla Albertina Dantas
name: De Melo Vilar, Kamila
name: De Nóbrega, Marcelo Francisco
name: De Almeida, Anderson Rodrigues
name: Michelly Cristiny Pereira
name: Dantas, Andréa Tavares
name: Gonçalves, Rafaela Silva Guimarães
name: Moacyr Jesus Barreto De Melo Rêgo
name: Duarte, Angela Luzia Branco Pinto
name: Da Rocha Pitta, Maira Galdino
Publisher: name: Taylor & Francis
Year: 2021
Subjects: subject: Biochemistry
subject: Medicine
subject: Cell Biology
subject: Genetics
subject: FOS: Biological sciences
subject: FOS: Biological sciences
subject: Biotechnology
subject: Ecology
subject: Immunology
subject: FOS: Clinical medicine
subject: FOS: Clinical medicine
subject: Developmental Biology

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