The Effect of ACTN3 and VDR Polymorphisms on Skeletal Muscle Performance in Axial Spondyloarthropathies

Isabel Pimenta; Hugo Mateus; Santiago Rodrigues-Manica; Rita Pinheiro-Torres; Agna Neto; Lúcia Domingues; Carolina Lage Crespo; Atlas Sardoo; Pedro Machado; Jaime C Branco; Susana N Silva; Fernando M Pimentel-Santos

doi:10.3389/fgene.2021.688984

The Effect of ACTN3 and VDR Polymorphisms on Skeletal Muscle Performance in Axial Spondyloarthropathies

Front Genet. 2021 Aug 11:12:688984. doi: 10.3389/fgene.2021.688984. eCollection 2021.

Authors

Isabel Pimenta^{1

2}, Hugo Mateus^{1

3}, Santiago Rodrigues-Manica^{1

4}, Rita Pinheiro-Torres^{1

4}, Agna Neto^{1

4}, Lúcia Domingues^{1

5}, Carolina Lage Crespo¹, Atlas Sardoo^{1

6}, Pedro Machado⁷, Jaime C Branco^{1

4}, Susana N Silva⁸, Fernando M Pimentel-Santos^{1

4}

Affiliations

¹ Chronic Diseases Research Center (CEDOC), NOVA Medical School, Universidade Nova de Lisboa, Lisboa, Portugal.
² Faculdade de Ciências, Universidade de Lisboa, Lisboa, Portugal.
³ Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, Lisboa, Portugal.
⁴ Centro Hospitalar de Lisboa Ocidental, Hospital de Egas Moniz, Serviço de Reumatologia, Lisboa, Portugal.
⁵ Instituto Politécnico de Setúbal, Escola Superior de Saúde, Setúbal, Portugal.
⁶ Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Lisboa, Portugal.
⁷ Centre for Rheumatology and Department of Neuromuscular Diseases, University College London, London, United Kingdom.
⁸ Center for Toxicogenomics and Human Health (ToxOmics), NOVA Medical School, Universidade Nova de Lisboa, Lisboa, Portugal.

Abstract

Background: Spondyloarthritis (SpA) are the most common group of chronic inflammatory rheumatic diseases affecting about 1.5% of the adult Caucasian population. Low back pain is the most common symptom. The aetiopathogenesis of SpA is multifactorial, with well-known genetic and environmental contributions. Furthermore, muscle properties might also be involved in the pathophysiological process and these could be modulated by the genetic background. Alpha-actinin-3 (ACTN3) and Vitamin D receptor (VDR) genes are well-known genes related with muscle performance. Our aim was to analyze four SNPs of these genes and to evaluate their influence in axial SpA (axSpA) susceptibility, phenotype and muscle properties.

Methods: We performed a pilot study based on case-control approach involving 56 participants: 28 axSpA patients and 28 healthy controls matched by age, gender and levels of physical activity. Clinical, epidemiological and muscle characterization data-muscle physical properties (stiffness, tone, and elasticity), strength, mass, and performance, were collected. Two different muscles were considered for analysis, the Multifidus and Gastrocnemius. Four SNPs of ACTN3 (rs1815739) and VDR (rs2228570, rs731236, and rs7975232), were selected, analyzed and correlated with clinical, epidemiological and muscle characterization data.

Results: In total, 51 individuals (27 axSpA patients and 24 matched controls) were eligible for further genetic analysis, 66.7% being male and with a mean age of 36 years. Muscle physical properties, muscle strength and muscle mass were similar in both groups; however, axSpA patients showed a decrease in muscle performance. None of the studied SNPs were associated with disease susceptibility/phenotype, muscle physical properties, muscle strength or muscle mass. However, ACTN3 rs1815739 and VDR rs2228570 were shown to be associated with muscle performance.

Conclusion: Our results suggest an association between ACTN3 and VDR polymorphisms and muscle performance in axSpA.

Keywords: ACTN3; VDR; muscle; muscle performance; spondyloarthropathies.