The Transforming Growth Factor β Genes and Susceptibility to Musculoskeletal Injuries in a Physically Active Caucasian Cohort

Sep 30, 2026

Changes in transforming growth factor-beta (TGF-β) family activity driven by genetic variability may shape musculoskeletal phenotype and influence sports-injury risk. This study tested whether polymorphisms in TGFBI (rs1442), TGFBR3 (rs1805113, rs1805117), and MSTN (rs11333758), separately or combined, relate to susceptibility to muscle injury, ACL rupture, and other injuries. Genotyping covered 202 physically active Caucasians with sport injuries and 133 controls, with statistical evaluation including Bonferroni correction.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages19

Reading Time48 min

AccessFree to download

Abstract

1. Introduction

TGF-β family roles in musculoskeletal biology

Myostatin (MSTN) and ECM remodeling

Rationale for studying gene polymorphisms in injury risk

Article The Transforming Growth Factor β Genes and Susceptibility to Musculoskeletal Injuries in a Physically Active Caucasian Cohort Agata Rzeszutko-Bełzowska 1, * and Agata Leo ´nska-Duniec 2 Academic Editor: Zan Gao Received: 13 November 2025 Revised: 23 December 2025 Accepted: 31 December 2025 Published: 3 January 2026 Copyright: © 2026 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license. 1 Faculty of Physical Culture Sciences, College of Medical Sciences, University of Rzeszow, 35-326 Rzeszow, Poland 2 Faculty of Physical Education, Gdansk University of Physical Education and Sport, 80-336 Gdansk, Poland; [agata.leonska-duniec@awf.gda.pl](agata.leonska-duniec@awf.gda.pl) * Correspondence: [arzeszutko@ur.edu.pl](arzeszutko@ur.edu.pl) Abstract Background/Objectives: Changes in the physiological activity of transforming growth factor-beta (TGF-β) family caused by genetic variability may significantly affect the phenotype of the musculoskeletal system and, consequently, the risk of sports injuries. This study aimed to investigate whether the TGFBI (rs1442), TGFBR3 (rs1805113 and rs1805117), and MSTN (rs11333758) polymorphisms, either individually or in combination, were associated with susceptibility to muscle injury, anterior cruciate ligament (ACL) rupture, and other injuries. Methods: The study group included 202 physically active Caucasians with reported sport injuries and 133 healthy controls. All the samples were genotyped using real-time polymerase chain reaction (real-time PCR) . Results: The results revealed that (1) the TGFBR3 rs1805117 TC genotype was nominally associated with increased ACL injury risk; (2) the MSTN rs11333758 heterozygotes was more frequent in the one injury group (vs controls) and in the ACL group, whereas [in the multiple vs. one](in the multiple vs. one) comparison the over-dominant model suggested lower odds for heterozygotes; and (3) the TGFBI rs1442 CG genotype was nominally associated with lower odds of fractures, dislocations or sprains. In addition, simultaneous analysis of chosen SNPs revealed interactions between TGFBR3 rs1805117 and rs1805113, with a nominal association of the rs1805113 G allele with increased injury risk, as did rs11333758 and rs1805113, with a potential effect of rs11333758 on injury status. However, haplotype analysis of the TGFBR3 SNPs revealed no significant associations. After Bonferroni correction, none of the associations remained statistically significant. Conclusions: The results suggested that carrying specific TGFBI, TGFBR3, and MSTN genotypes may be potentially associated with susceptibility to musculoskeletal injuries in a physically active Caucasians. Keywords: TGFBI; TGFBR3; MSTN; sport; ACL rupture; muscle injury 1. Introduction The adaptive capacity of skeletal muscle and tendons to changing external factors, such as the volume and intensity of exercise, as well as previous injuries and other physiological conditions, is a key element in determining an individual’s overall mobility, athletic ability, and health. The close anatomical connection between musculoskeletal structures and the shared microcirculation and interstitial fluid suggests efficient communication between these tissues mediated by activated transforming growth factor-beta (TGF-β) family members [1] . This family consists of more than 50 molecules that are structurally related, namely, numerous peptide growth and differentiation factors, including activins, bone morphogenetic proteins (BMPs), growth and differentiation factors (GDFs), and three isoforms, namely, TGF-β 1–3. Among them, GDF8, also known as myostatin (MSTN), is a negative regulator of skeletal muscle growth and development [2,3] . Biological processes under the regulation of TGF-β, specifically myoblast and fibroblast cell survival, growth, differentiation

FAQs

Which gene polymorphisms were investigated in relation to musculoskeletal injuries?

The study assessed TGFBI (rs1442), TGFBR3 (rs1805113 and rs1805117), and MSTN (rs11333758), evaluated individually and in combination.

How was the study designed and who were the participants?

It included 202 physically active Caucasians who reported sport injuries and 133 healthy controls. All samples were genotyped using real-time PCR.

Did any associations remain significant after multiple-testing correction?

After Bonferroni correction, none of the associations remained statistically significant, despite nominal findings reported before correction.

Sep 30, 2026

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