Genetic factors contributing to the development of inguinal hernias – a narrative review
DOI:
https://doi.org/10.15584/ejcem.2024.2.2Keywords:
genes, genetics, genome-wide association, inguinal hernias, polymorphisms, studiesAbstract
Introduction and aim. Inguinal hernias are one of the major disorders in the field of general and visceral surgery and can be viewed as multifactorial diseases. Although the molecular mechanism that led to predistortion to inguinal herniation still remain unclear, is well known that defects leading to improper closure of the inguinal canal during fetal development and mechanisms contributing to weaker muscles of the abdominal wall can greatly increase the risk of developing the latter disease.
Material and methods. A literature search was performed in all major electronic databases using keywords and Boolean operators to retrieve all available literature related to the topic. Due to the narrative nature of the review, there were no specific inclusion and exclusion criteria.
Analysis of the literature. Genetic factors, undoubtedly, can interfere with these mechanisms and therefore play major role in developing hernias. To this end, the present narrative review provides an overview of genes with altered expression and genetic polymorphisms associated with inguinal herniation. Moreover, the results of genome-wide association studies (GWAS) exploring susceptible genetic loci associated with the disease have been reported.
Conclusion. Nevertheless, more case-control studies and GWAS need to be conducted in different ethnic populations so as to provide better insights into the topic.
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References
Abebe MS, Tareke AA, Alem A, Debebe W, Beyene A. Worldwide magnitude of inguinal hernia: Systematic review and meta-analysis of population-based studies. SAGE Open Med. 2022;10:20503121221139150. doi: 10.1177/20503121221139150
Holzheimer RG. Inguinal Hernia: classification, diagnosis and treatment--classic, traumatic and Sportsman's hernia. Eur J Med Res. 2005;10(3):121-134.
Shakil A, Aparicio K, Barta E, Munez K. Inguinal Hernias: Diagnosis and Management. Am Fam Physician. 2020;102(8):487-492.
Öberg S, Andresen K, Rosenberg J. Etiology of Inguinal Hernias: A Comprehensive Review. Front Surg. 2017;4:52. doi: 10.3389/fsurg.2017.00052
Yeap E, Pacilli M, Nataraja RM. Inguinal hernias in children. Aust J Gen Pract. 2020;49(1-2):38-43. doi: 10.31128/ajgp-08-19-5037
O'Brien J, Sinha S, Turner R. Inguinal hernia repair: a global perspective. ANZ J Surg. 2021;91(11):2288-2295. doi: 10.1111/ans.17174
Campanelli G, Pettinari D, Nicolosi FM, Cavalli M, Avesani EC. Inguinal hernia recurrence: classification and approach. Hernia. 2006;10(2):159-161. doi: 10.1007/s10029-005-0053-3
Carbonell JF, Sanchez JL, Peris RT, et al. Risk factors associated with inguinal hernias: a case control study. Eur J Surg. 1993;159(9):481-486.
Burcharth J, Pommergaard HC, Bisgaard T, Rosenberg J. Patient-related risk factors for recurrence after inguinal hernia repair: a systematic review and meta-analysis of observational studies. Surg Innov. 2015;22(3):303-317. doi: 10.1177/1553350614552731
Öberg S, Sæter AH, Rosenberg J. The inheritance of groin hernias: an updated systematic review with meta-analyses. Hernia. 2022;27(6):1339-1350. doi: 10.1007/s10029-022-02718-3
Csapo R, Gumpenberger M, Wessner B. Skeletal Muscle Extracellular Matrix – What Do We Know About Its Composition, Regulation, and Physiological Roles? A Narrative Review. Review. Front Physiol. 2020;11:253. doi: 10.3389/fphys.2020.00253
Rozario T, DeSimone DW. The extracellular matrix in development and morphogenesis: a dynamic view. Dev Biol. 2010;341(1):126-140. doi: 10.1016/j.ydbio.2009.10.026
Walma DAC, Yamada KM. The extracellular matrix in development. Development. 2020;147(10): 175596. doi: 10.1242/dev.175596
Naba A, Clauser KR, Ding H, Whittaker CA, Carr SA, Hynes RO. The extracellular matrix: Tools and insights for the “omics” era. Matrix Biology. 2016;49:10-24. doi: 10.1016/j.matbio.2015.06.003
Harrison B, Sanniec K, Janis JE. Collagenopathies—Implications for Abdominal Wall Reconstruction: A Systematic Review. Plastic and Reconstructive Surgery – Global Open. 2016;4(10):1036. doi: 10.1097/gox.0000000000001036
Kral JG, Levine RG. Increases in type III collagen gene expression and protein synthesis in patients with inguinal hernias. Ann Surg. 1995;221(1):116-117.
Asgari M, Latifi N, Heris HK, Vali H, Mongeau L. In vitro fibrillogenesis of tropocollagen type III in collagen type I affects its relative fibrillar topology and mechanics. Sci Rep. 2017;7(1):1392. doi: 10.1038/s41598-017-01476-y
Meyer AL, Berger E, Monteiro O, Jr., Alonso PA, Stavale JN, Gonçalves MP. Quantitative and qualitative analysis of collagen types in the fascia transversalis of inguinal hernia patients. Arq Gastroenterol. 2007;44(3):230-234. doi: 10.1590/s0004-28032007000300010
Rodrigues Junior AJ, Rodrigues CJ, da Cunha AC, Jin Y. Quantitative analysis of collagen and elastic fibers in the transversalis fascia in direct and indirect inguinal hernia. Rev Hosp Clin Fac Med Sao Paulo. 2002;57(6):265-270. doi: 10.1590/s0041-87812002000600004
Holle AW, Young JL, Van Vliet KJ, et al. Cell–Extracellular Matrix Mechanobiology: Forceful Tools and Emerging Needs for Basic and Translational Research. Nano Letters. 2018;18(1):1-8. doi: 10.1021/acs.nanolett.7b04982
Peng X, Guo Z, Zhang Y, Sun B, Zhang Q. EFEMP1 in Direct Inguinal Hernia: correlation with TIMP3 and Regulation Toward Elastin Homoeostasis as Well as Fibroblast Mobility. J Invest Surg. 2022;35(1):203-211. doi: 10.1080/08941939.2020.1811812
Rymen D, Ritelli M, Zoppi N, et al. Clinical and Molecular Characterization of Classical-Like Ehlers-Danlos Syndrome Due to a Novel TNXB Variant. Genes (Basel). 2019;10(11):843. doi: 10.3390/genes10110843
Klinge U, Zheng H, Si ZY, Schumpelick V, Bhardwaj R, Klosterhalfen B. Synthesis of type I and III collagen, expression of fibronectin and matrix metalloproteinases-1 and -13 in hernial sac of patients with inguinal hernia. Int J Surg Investig. 1999;1(3):219-227.
Taghavi K, Geneta vP, Mirjalili SA. The pediatric inguinal canal: Systematic review of the embryology and surface anatomy. Clinical Anatomy. 2016;29(2):204-210. doi: 10.1002/ca.22633
Skandalakis JE, Colborn GL, Androulakis JA, Skandalakis LJ, Pemberton LB. Embryologic And Anatomic Basis Of Inguinal Herniorrhaphy. Surgical Clinics of North America. 1993;73(4):799-836. doi: 10.1016/S0039-6109(16)46086-X
Mouravas VK, Koletsa T, Sfougaris DK, et al. Smooth muscle cell differentiation in the processus vaginalis of children with hernia or hydrocele. Hernia. 2010;14(2):187-191. doi: 10.1007/s10029-009-0588-9
Hutson JM, Albano FR, Paxton G, et al. In vitro fusion of human inguinal hernia with associated epithelial transformation. Cells Tissues Organs. 2000;166(3):249-258. doi: 10.1159/000016738
Sezer S, Şimşek N, Celik HT, et al. Association of collagen type I alpha 1 gene polymorphism with inguinal hernia. Hernia. 2014;18(4):507-512. doi: 10.1007/s10029-013-1147-y
Stępien-Słodkowska M, Ficek K, Eider J, et al. The +1245g/t polymorphisms in the collagen type I alpha 1 (col1a1) gene in polish skiers with anterior cruciate ligament injury. Biol Sport. 2013;30(1):57-60. doi: 10.5604/20831862.1029823
Wu J, Yu M, Zhou Y. Association of collagen type I alpha 1 +1245G/T polymorphism and osteoporosis risk in post-menopausal women: a meta-analysis. International Journal of Rheumatic Diseases. 2017;20(7):903-910. doi: 10.1111/1756-185X.13052
Chang HH, Juan YS, Li CC, Lee HY, Chen JH. Congenital collagenopathies increased the risk of inguinal hernia developing and repair: analysis from a nationwide population-based cohort study. Sci Rep. 2022;12(1):2360. doi: 10.1038/s41598-022-06367-5
Duque Lasio ML, Kozel BA. Elastin-driven genetic diseases. Matrix Biol. 2018;71-72:144-160. doi: 10.1016/j.matbio.2018.02.021
Rodrigues C, Yoo J, Junior A. Elastin (ELN) gene point mutation in patients with inguinal hernia. Genet Mol Biol. 2006;29:45-46. doi: 10.1590/S1415-47572006000100009
Zhang MC, He L, Giro M, Yong SL, Tiller GE, Davidson JM. Cutis laxa arising from frameshift mutations in exon 30 of the elastin gene (ELN). J Biol Chem. 1999;274(2):981-986. doi: 10.1074/jbc.274.2.981
Kun Y, Mengdong S, Cong F, Ran H. Congenital Cutis Laxa: A Case Report and Literature Review. Case Report. Front Surg. 2022;9:814897. doi: 10.3389/fsurg.2022.814897
Van Doren SR. Matrix metalloproteinase interactions with collagen and elastin. Matrix Biology. 2015;44-46:224-231. doi: 10.1016/j.matbio.2015.01.005
Arpino V, Brock M, Gill SE. The role of TIMPs in regulation of extracellular matrix proteolysis. Matrix Biology. 2015;44-46:247-254. doi: 10.1016/j.matbio.2015.03.005
Antoniou GA, Tentes IK, Antoniou SA, Simopoulos C, Lazarides MK. Matrix Metalloproteinase Imbalance in Inguinal Hernia Formation. Journal of Investigative Surgery. 2011;24(4):145-150. doi: 10.3109/08941939.2011.558610
Isik A, Gursul C, Peker K, Aydın M, Fırat D, Yılmaz İ. Metalloproteinases and Their Inhibitors in Patients with Inguinal Hernia. World J Surg. 2017;41(5):1259-1266. doi: 10.1007/s00268-016-3858-6
Serra R, Buffone G, Costanzo G, et al. Altered metalloproteinase-9 expression as least common denominator between varicocele, inguinal hernia, and chronic venous disorders. Ann Vasc Surg. 2014;28(3):705-709. doi: 10.1016/j.avsg.2013.07.026
Sugiyama H. WT1 (Wilms' tumor gene 1): biology and cancer immunotherapy. Jpn J Clin Oncol. 2010;40(5):377-387. doi: 10.1093/jjco/hyp194
Yen HC, Chen IC, Lin GC, et al. Sex-specific genetic variants associated with adult-onset inguinal hernia in a Taiwanese population. Int J Med Sci. 2023;20(5):607-615. doi: 10.7150/ijms.82331
Livingstone I, Uversky VN, Furniss D, Wiberg A. The Pathophysiological Significance of Fibulin-3. Biomolecules. 2020;10(9):1294. doi: 10.3390/biom10091294
Papaioannou VE. The T-box gene family: emerging roles in development, stem cells and cancer. Development. 2014;141(20):3819-3833. doi: 10.1242/dev.104471
Zhang Y, Han Q, Fan H, Li W, Xing Q, Yan B. Genetic analysis of the TBX2 gene promoter in indirect inguinal hernia. Hernia. 2014;18(4):513-517. doi: 10.1007/s10029-013-1199-z
Zhao Z, Tian W, Wang L, et al. Genetic and functional analysis of the TBX3 gene promoter in indirect inguinal hernia. Gene. 2015;554(1):101-104. doi: 10.1016/j.gene.2014.10.031
Chen D, Qiao Y, Meng H, et al. Genetic analysis of the TBX3 gene promoter in ventricular septal defects. Gene. 2013;512(2):185-188. doi: 10.1016/j.gene.2012.10.066
Pang S, Liu Y, Zhao Z, Huang W, Chen D, Yan B. Novel and functional sequence variants within the TBX2 gene promoter in ventricular septal defects. Biochimie. 2013;95(9):1807-1809. doi: 10.1016/j.biochi.2013.05.007
Greene AG, Eivers SB, Dervan EWJ, O'Brien CJ, Wallace DM. Lysyl Oxidase Like 1: Biological roles and regulation. Exp Eye Res. 2020;193:107975. doi: 10.1016/j.exer.2020.107975
Pascual G, Rodríguez M, Mecham RP, Sommer P, Buján J, Bellón JM. Lysyl oxidase like-1 dysregulation and its contribution to direct inguinal hernia. Eur J Clin Invest. 2009;39(4):328-337. doi: 10.1111/j.1365-2362.2009.02099.x
Vallet SD, Ricard-Blum S. Lysyl oxidases: from enzyme activity to extracellular matrix cross-links. Essays Biochem. 2019;63(3):349-364. doi: 10.1042/ebc20180050
Houtkooper RH, Pirinen E, Auwerx J. Sirtuins as regulators of metabolism and healthspan. Nat Rev Mol Cell Biol. 2012;13(4):225-238. doi: 10.1038/nrm3293
Han Q, Zhang Y, Li W, et al. Functional sequence variants within the SIRT1 gene promoter in indirect inguinal hernia. Gene. 2014;546(1):1-5. doi: 10.1016/j.gene.2014.05.058
Jorgenson E, Makki N, Shen L, et al. A genome-wide association study identifies four novel susceptibility loci underlying inguinal hernia. Nat Commun. 2015;6:10130. doi: 10.1038/ncomms10130
Hikino K, Koido M, Tomizuka K, et al. Susceptibility loci and polygenic architecture highlight population specific and common genetic features in inguinal hernias: genetics in inguinal hernias. EBioMedicine. 2021;70:103532. doi: 10.1016/j.ebiom.2021.103532
Ahmed WU-R, Patel MIA, Ng M, et al. Shared genetic architecture of hernias: A genome-wide association study with multivariable meta-analysis of multiple hernia phenotypes. PLOS ONE. 2022;17(12):0272261. doi: 10.1371/journal.pone.0272261
Choquet H, Li W, Yin J, et al. Ancestry- and sex-specific effects underlying inguinal hernia susceptibility identified in a multiethnic genome-wide association study meta-analysis. Human Molecular Genetics. 2022;31(13):2279-2293. doi: 10.1093/hmg/ddac003
Fadista J, Skotte L, Karjalainen J, et al. Comprehensive genome-wide association study of different forms of hernia identifies more than 80 associated loci. Nat Com. 2022;13(1):3200. doi: 10.1038/s41467-022-30921-4
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