Genetic variants involved in extracellular matrix homeostasis play a role in the susceptibility to frozen shoulder: A case-control study

Author(s):Show less -

Cohen, Carina ^[1] ; Leal, Mariana F. ^{[1, 2]} ; Loyola, Leonor C. ^{[1, 2]} ; Santos, Sidney E. B. ^[3] ; Ribeiro-dos-Santos, Andrea K. C. ^[3] ; Belangero, Paulo S. ^[1] ; Figueiredo, Eduardo A. ^[1] ; Wajnsztejn, Andre ^[1] ; de Oliveira, Adrielle M. ^{[1, 2]} ; Smith, Marilia C. ^[2] ; Andreoli, Carlos V. ^[1] ; Pochini, Alberto de Castro ^[1] ; Cohen, Moises ^[1] ; Ejnisman, Benno ^[1] ; Faloppa, Flavio ^[1]

Affiliation

^[1] Univ Fed Sao Paulo, Dept Ortopedia & Traumatol, Sao Paulo, SP - Brazil

^[2] Univ Fed Sao Paulo, Dept Morfol & Genet, Disciplina Genet, Sao Paulo, SP - Brazil

^[3] Univ Fed Para, Lab Genet Humana & Med, Inst Ciencias Biol, Belem, Para - Brazil

• Document type: Journal article
• Source: JOURNAL OF ORTHOPAEDIC RESEARCH; v. 37, n. 4, p. 948-956, APR 2019.
• Web of Science Citations: 1

Abstract

Frozen shoulder is a condition of loss of active and passive motion as result of inflammatory contracture and fibrosis of the joint capsule. We hypothesize that genetic variants in genes involved in these processes such as genes that play a role in extracellular matrix homeostasis (collagens, glycoproteins, genes involved in TGF beta signaling, and metalloproteinases and its inhibitors) may contribute to the susceptibility to frozen shoulder. We evaluated eighteen SNPs of genes involved in extracellular matrix homeostasis in 186 cases (N-females = 114; N-males = 72) of frozen shoulder and 600 age-matched controls (N-females = 308; N-males = 292). Multivariate logistic regressions were carried out with age, gender, genetic ancestry, and common comorbidities as covariates. Carriers of the C allele of MMP13 rs2252070 and G/G MMP9 (rs17576 A>G/rs17577 G>A) haplotype may have an increased risk of frozen shoulder (p = 0.002, OR = 1.64, 95%CI = 1.20-2.26, and p = 0.046, OR = 1.40, 95%CI = 1.01-1.95, respectively), especially in females (p = 0.005, OR = 1.91, 95%CI = 1.22-2.99, and p = 0.046, OR = 1.59, 95%CI = 1.01-2.51, respectively). In females, the G allele of MMP9 rs17576 tended to contribute to the susceptibility to the studied disease (p = 0.05, OR = 1.51, 95%CI = 0.97-2.33). In contrast, the presence of the C allele of TGFB1 rs1800470 seems to be associated with a reduced risk (p = 0.04, OR = 0.47, 95%CI = 0.23-0.96) while the GG-genotype of TGFBR1 rs1590 was associated with increased risk (p = 0.027, OR = 4.11, 95%CI = 1.17-14.38) to frozen shoulder development in males. Thus, we identified genetic variants that were independent risk factors that can aid in the risk assessment of frozen shoulder reinforcing the involvement of MMP and TGF beta signaling in disease development. (c) 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res (AU)

• FAPESP's process: 11/22548-2 - Nontraumatic orthopedic conditions of shoulder: genetic and molecular aspects
• Grantee: Mariana Ferreira Leal
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 12/14768-5 - Nontraumatic orthopedic conditions of shoulder: genetic and molecular aspects
• Grantee: Mariana Ferreira Leal
• Support Opportunities: Scholarships in Brazil - Young Researchers
• FAPESP's process: 13/23332-9 - Expression and polymorphic variants analysis of fibronectin 1 and tenascin-C genes in rotator cuff tear
• Grantee: Leonor Isabel Casilla Loyola
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 15/02285-8 - Polymorphism analysis of extracellular matrix genes in anterior cruciate ligament injury
• Grantee: Leonor Isabel Casilla Loyola
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)