Rotator Cuff Tear Susceptibility Is Associated With Variants in Genes Involved in Tendon Extracellular Matrix Homeostasis

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Figueiredo, Eduardo A. ; Loyola, Leonor Casilla ; Belangero, Paulo S. ; Campos Ribeiro-dos-Santos, Andrea Kely ; Batista Santos, Sidney Emanuel ; Cohen, Carina ; Wajnsztejn, Andre ; de Oliveira, Adrielle Martins ; Smith, Marilia C. ; Pochini, Alberto de Castro ; Andreoli, Carlos V. ; Ejnisman, Benno ; Cohen, Moises ; Leal, Mariana F.

• Document type: Journal article
• Source: JOURNAL OF ORTHOPAEDIC RESEARCH; v. 38, n. 1, p. 10-pg., 2020-01-01.

Abstract

Rotator cuff tears (RCT) is a multifactorial disease with genetic factors contributing for the disease etiology. We hypothesized that genetic variants in genes involved in extracellular matrix (ECM) homeostasis may alter susceptibility to RCT. We evaluated 20 polymorphisms of genes involved in ECM homeostasis in 211 cases of full-thickness tears of the supraspinatus (N-females = 130; N-males = 81) and 567 age-matched controls (N-females = 317; N-males = 250). Multivariate logistic regressions were carried out with age, gender, genetic ancestry (based on the analysis of 61 biallelic short insertion/deletion polymorphisms), and common co-morbidities (diabetes, dyslipidemia, and smoking habits) as covariates. We observed that carriers of the rare allele of both studied variants of TGFB1, as well as their G/A (rs1800470/rs1800469) haplotype, were less susceptible to RCT (p < 0.05). In contrast, carriers of the G allele of MMP9 rs17576 (p = 0.014) or G/G haplotype (rs17576/rs17577; p < 0.001) had an increased risk for tendon tears. The presence of the T allele of MMP2 rs2285053 (p = 0.033), the T allele of MMP3 rs679620 (p = 0.024), and the TT-genotype of TIMP2 rs2277698 (p = 0.01) was associated with susceptibility to tears, especially in females. In males, the A allele of COL5A1 rs3196378 (p = 0.032) and the G allele of TGFBR1 rs1590 (p = 0.039) were independent risk factors for RCT. The C/T COL5A1 (rs3196378/rs11103544) haplotype was associated with a reduced risk of tears in males (p = 0.03). In conclusion, we identified the genetic variants associated with RCT susceptibility, thereby reinforcing the role of genes involved in the structure and homeostasis of the ECM of tendons in disease development. (C) 2019 Orthopedic Research Society. Published by Wiley Periodicals, Inc. (AU)

• 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)
• 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: 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: 12/14768-5 - Nontraumatic orthopedic conditions of shoulder: genetic and molecular aspects
• Grantee: Mariana Ferreira Leal
• Support Opportunities: Scholarships in Brazil - Young Researchers