Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 2.1
5-Year Impact Factor – 2.2
Scopus CiteScore – 3.4 (CiteScore Tracker 3.4)
Index Copernicus  – 161.11; MEiN – 140 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

Download original text (EN)

Advances in Clinical and Experimental Medicine

2020, vol. 29, nr 5, May, p. 623–628

doi: 10.17219/acem/118846

Publication type: review article

Language: English

License: Creative Commons Attribution 3.0 Unported (CC BY 3.0)

Download citation:

  • BIBTEX (JabRef, Mendeley)
  • RIS (Papers, Reference Manager, RefWorks, Zotero)

The role of genetic factors in carpal tunnel syndrome etiology: A review

Andrzej Żyluk1,A,B,C,D,E,F

1 Clinic of General and Hand Surgery, Pomeranian Medical University in Szczecin, Poland

Abstract

The direct causes of idiopathic carpal tunnel syndrome (CTS) still remain obscure. It has been suggested that the pathology of tendons and other connective tissue structures within the carpal tunnel may be involved in its etiology. The objective of this study was to review the literature about the potential role of genetic factors in the etiology of CTS. Three different mechanisms are suspected to be involved in genetic predisposition to CTS: collagen synthesis, collagen degradation and protection against oxidative stress effect in connective tissue. Several gene groups are involved in the regulation and modulation of these mechanisms, and the research reviewed in this study showed their possible effect on the development of CTS. Variants within the COL1A1, COL5A1 and COL11A1 genes – encoding the synthesis of minor collagen subtypes – may potentially be involved, as they alter the mechanical properties of tendons and other connective tissue structures within the carpal tunnel. The collagen within connective tissue structures is also remodeled by matrix metalloproteinases (MMPs), so variants of these genes have also been investigated for their possible role in the risk of CTS development. Next, the variants of genes encoding glutathione S-transferase (GST) synthesis were found to be involved in the etiology of CTS. The findings from the abovementioned studies provide reliable information on the potential role of genetic risk factors in the development of CTS.

Key words

genetic factors, collagen synthesis, gene variants, carpal tunnel syndrome etiology

References (25)

  1. Puchalski P, Zyluk P, Szlosser Z, Zyluk A. Factors involving the clinical profile of carpal tunnel syndrome. Handchir Mikrochir Plast Chir. 2018;50(1):8–13.
  2. Burger M, de Wet H, Collins M. The BGN and ACAN genes and carpal tunnel syndrome. Gene. 2014;551(2):160–166.
  3. Dada S, Burger MC, Massij F, de Wet H, Collins M. Carpal tunnel syndrome: The role of collagen gene variants. Gene. 2016;587(1):53–58. doi:10.1016/j.gene.2016.04.030
  4. Burger M, de Wet H, Collins M. The COL5A1 gene is associated with increased risk of carpal tunnel syndrome. Clin Rheumatol. 2014;34(4):767–774.
  5. Wenstrup RJ, Smith SM, Florer JB, et al. Regulation of collagen fibril nucleation and initial fibril assembly involves coordinate interactions with collagens V and XI in developing tendon. J Biol Chem. 2011;286(23):20455–20465.
  6. Ficek K, Cieszyk O, Kaczmarczyk M, et al. Gene variants within the COL1A1 gene are associated with reduced ACL injury in professional soccer players. J Sci Med Sport. 2013;16(5):396–400.
  7. Hay M, Patricos J, Collins R, et al. Association of type XI collagen genes with chronic Achilles tendinopathy in independent populations form South Africa and Australia. Br J Sports Med. 2013;47(9):569–574.
  8. Posthumus M, September AV, Keegan M, et al. Genetic risk factors for anterior cruciate ligament ruptures: COL1A1 gene variant. Br J Sports Med. 2009;43(5):352–356.
  9. Posthumus M, September AV, O’Cuinneagain D, van der Merwe W, Schwellnus MP, Collins M. The association between the COL12A1 gene and anterior cruciate ligament ruptures. Br J Sports Med. 2010;44(16):1160–1165.
  10. Mio F, Chiba K, Hirose Y, et al. A functional polymorphism in COL11A1, which encodes the alpha 1 chain of type XI collagen, is associated with susceptibility to lumbar disc herniation. Am J Hum Genet. 2007:81(6):1271–1277.
  11. Pasternak B, Aspenberg P. Metalloproteinases and their inhibitors: Diagnostic and therapeutic opportunities in orthopedics. Acta Orthop. 2009;80(6):693–703.
  12. Burger MC, De Wet H, Collins M. Matrix metalloproteinase genes on chromosome 11q22 and risk of carpal tunnel syndrome. Rheumatol Int. 2016;36(3):413–419. doi:10.1007/s00296-015-3385-z
  13. Raleigh SM, van der Merwe L, Ribbans WJ, Smith RK, Schwellnus MP, Collins M. Variants within the MMP3 gene are associated with Achilles tendinopathy: Possible interaction with the COL5A1 gene. Br J Sport Med. 2009;43(7):514–520.
  14. Posthumus M, Collins M, van der Merwe L, et al. Matrix metalloproteinase genes on chromosome 11q22 and the risk of ACL rupture. Scand J Med Sci Sport. 2012;22(4):523–533.
  15. Somerville RP, Oblader SA, Aptek SS. Matrix metalloproteinases: Old dogs with new tricks. Genome Biol. 2003;4(6):216. doi:10.1186/gb-2003-4-6-216
  16. Malila S, Yuktanandana P, Saowaprut S, Jiamjarasrangsi W, Honsawek S. Association between matrix metalloproteinase-3 polymorphism and ACL ruptures. Genet Mol Res. 2011;10(4):4158–4165.
  17. Kim JK, Koh YD, Hann HJ, Kim MJ. Oxidative stress in sub-synovial connective tissue of idiopathic carpal tunnel syndrome. J Orthop Res. 2010;28(11):1463–1468.
  18. Eroğlu P, Erkol İnal E, Sağ ŞÖ, Görükmez Ö, Topak A, Yakut T. Associations analysis of GSTM1, T1 and P1 Ile105Val polymorphisms with carpal tunnel syndrome. Clin Rheumatol. 2016;35(5):1245–1251. doi:10.1007/s10067-014-2855-0
  19. Board PG, Menon D. Glutathione transferases, regulator of cellular metabolism and physiology. Biochem Biophys Acta. 2013;1830(5):3267–3288.
  20. Ali-Osman F, Akande O, Antoun G, Mao XJ, Buolamwini J. Molecular cloning, characterization and expression in Escherichia coli of full-length cDNAs of three human GSTP1 variants: Evidence of catalytic activity of encoded proteins. J Biol Chem. 1007;272(15):10004–10012.
  21. Fernandez-de-Las-Penas C, Ambite-Quesada S, Fahandezh-Saddi Díaz H, Paras-Bravo P, Palacios-Cena D, Cuadrado ML. The Val158Met poly-morphism of the catechol-O-methyltransference gene is not associated with long-term treatment outcomes in carpal tunnel syndrome: A randomized clinical trial. PLoS One. 2018;13(10):e0205516. doi:10.1371/journal.pone.0205516
  22. Cevik B, Tekcan A, Inanir A, Kurt SG, Yigit S. The investigation of association between IL-1Ra and ACE I/D polymorphisms in carpal tunnel syndrome. J Clin Lab Anal. 2018;32(1):e22204. doi:10.1002/jcla.22204
  23. Puchalski P, Szlosser Z, Zyluk A. Familial occurrence of carpal tunnel syndrome. Neurol Neurochir Pol. 2019;53(1):43–46. doi:105603/PJNNS.a2019.0004
  24. Gossett JG, Chance PF. Is there a familial carpal tunnel syndrome? An evaluation and literature review. Muscle Nerve. 1998;21(11):1533–1536.
  25. Alford JW, Weiss AP, Akelman E. The familial incidence of carpal tunnel syndrome in patients with unilateral and bilateral disease. AmJ Orthop (Belle Mead NJ). 2004;33(8):397–400.
© Wroclaw Medical University