Genetic Variants in Matrix Metalloproteinases (rs3025058) and (rs3918242) Associated with Colonic Diverticulosis

Overview

Journal Medicina (Kaunas)

Publisher MDPI

Specialty General Medicine

Date 2023 Nov 25

PMID 38004080

Authors

Piotr Nehring

Grazyna Gromadzka

Milosz Jastrzebski

Adam Przybylkowski

Affiliations

Soon will be listed here.

Abstract

: Diverticulosis affects a significant portion of the elderly population, with age and lifestyle being established risk factors. Additionally, genetic predisposition is gaining recognition as a contributing factor. This pilot study sought to explore the frequency of genetic variants in matrix metalloproteinases (MMPs) 3, 9, and 12 in a population of colonic diverticulosis patients. : The study encompassed 134 participants: 59 diagnosed with colon diverticulosis during colonoscopy and 75 healthy controls. The cases and controls were meticulously matched in terms of age and gender. We assessed the distribution of genetic variants rs3025058, rs3918242, and rs2276109 using the polymerase chain reaction-restriction fragments length polymorphism technique. : The rs3918242 allele T was notably more frequent in individuals with diverticulosis when compared with the control group ( < 0.03). Furthermore, it was associated with dominant (OR = 2.62; 95% CI: 1.24-5.56; < 0.01) and co-dominant (OR = 2.10; 95% CI: 1.06-4.13; < 0.03) genetic models. The rs3025058 5A/5A genotype was nearly twice as frequent in patients with diverticulosis, while the 6A/6A genotype was only half as common in this group. Conversely, no significant correlation was established between rs2276109 and colonic diverticulosis. : Our study offers the first insight into a potential connection between genetic variants in MMPs and colon diverticulosis. Specifically, allele T of rs3918242 and allele 5A of rs3025058 appear to be linked to this condition. These findings indirectly suggest a role for extracellular matrix proteins in the pathogenesis of diverticulosis.

References

Mastoraki A, Schizas D, Tousia A, Chatzopoulos G, Gkiala A, Syllaios A . Evaluation of molecular and genetic predisposing parameters at diverticular disease of the colon. Int J Colorectal Dis. 2021; 36(5):903-910. DOI: 10.1007/s00384-020-03812-7. View

Reichert M, Lammert F . The genetic epidemiology of diverticulosis and diverticular disease: Emerging evidence. United European Gastroenterol J. 2015; 3(5):409-18. PMC: 4625748. DOI: 10.1177/2050640615576676. View

Raeeszadeh-Sarmazdeh M, Do L, Hritz B . Metalloproteinases and Their Inhibitors: Potential for the Development of New Therapeutics. Cells. 2020; 9(5). PMC: 7290391. DOI: 10.3390/cells9051313. View

Schafmayer C, Harrison J, Buch S, Lange C, Reichert M, Hofer P . Genome-wide association analysis of diverticular disease points towards neuromuscular, connective tissue and epithelial pathomechanisms. Gut. 2019; 68(5):854-865. DOI: 10.1136/gutjnl-2018-317619. View

Lorente L, Martin M . The 372 T/C genetic polymorphism of TIMP-1 as a biomarker of mortality in patients with sepsis. Crit Care. 2013; 17(5):456. PMC: 4014811. DOI: 10.1186/cc13037. View

Peery A, Barrett P, Park D, Rogers A, Galanko J, Martin C . A high-fiber diet does not protect against asymptomatic diverticulosis. Gastroenterology. 2011; 142(2):266-72.e1. PMC: 3724216. DOI: 10.1053/j.gastro.2011.10.035. View

Williamson B . Lower Gastrointestinal Conditions: Diverticular Disease. FP Essent. 2019; 483:25-29. View

Krishnaveni D, Bhayal A, Shravan K, Jyothy A, Pratibha N, Venkateshwari A . Heterozygosity of stromelysin-1 (rs3025058) promoter polymorphism is associated with gastric cancer. Indian J Cancer. 2016; 52(2):251-4. DOI: 10.4103/0019-509X.175806. View

Vu T, Werb Z . Matrix metalloproteinases: effectors of development and normal physiology. Genes Dev. 2000; 14(17):2123-33. DOI: 10.1101/gad.815400. View

10.

Peery A, Keku T, Addamo C, Mccoy A, Martin C, Galanko J . Colonic Diverticula Are Not Associated With Mucosal Inflammation or Chronic Gastrointestinal Symptoms. Clin Gastroenterol Hepatol. 2017; 16(6):884-891.e1. PMC: 5722710. DOI: 10.1016/j.cgh.2017.05.051. View

11.

Nehring P, Gromadzka G, Giermaziak A, Jastrzebski M, Przybylkowski A . Genetic variants of tissue inhibitors of matrix metalloproteinase 1 (rs4898) and 2 (rs8179090) in diverticulosis. Eur J Gastroenterol Hepatol. 2021; 33(1S Suppl 1):e431-e434. DOI: 10.1097/MEG.0000000000002122. View

12.

Smigiel K, Parks W . Matrix Metalloproteinases and Leukocyte Activation. Prog Mol Biol Transl Sci. 2017; 147:167-195. DOI: 10.1016/bs.pmbts.2017.01.003. View

13.

Churg A, Wang R, Tai H, Wang X, Xie C, Wright J . Tumor necrosis factor-alpha drives 70% of cigarette smoke-induced emphysema in the mouse. Am J Respir Crit Care Med. 2004; 170(5):492-8. DOI: 10.1164/rccm.200404-511OC. View

14.

Chaudhary A, Singh M, Bharti A, Asotra K, Sundaram S, Mehrotra R . Genetic polymorphisms of matrix metalloproteinases and their inhibitors in potentially malignant and malignant lesions of the head and neck. J Biomed Sci. 2010; 17:10. PMC: 2846899. DOI: 10.1186/1423-0127-17-10. View

15.

Touzios J, Dozois E . Diverticulosis and acute diverticulitis. Gastroenterol Clin North Am. 2009; 38(3):513-25. DOI: 10.1016/j.gtc.2009.06.004. View

16.

Ho W, Chen C, Lee Y, Chang K, Chen H, Chen S . Association of MMP-9 Haplotypes and TIMP-1 Polymorphism with Spontaneous Deep Intracerebral Hemorrhage in the Taiwan Population. PLoS One. 2015; 10(5):e0125397. PMC: 4416754. DOI: 10.1371/journal.pone.0125397. View

17.

Talutis S, Kuhnen F . Pathophysiology and Epidemiology of Diverticular Disease. Clin Colon Rectal Surg. 2021; 34(2):81-85. PMC: 7904337. DOI: 10.1055/s-0040-1716698. View

18.

Maguire L, Handelman S, Du X, Chen Y, Pers T, Speliotes E . Genome-wide association analyses identify 39 new susceptibility loci for diverticular disease. Nat Genet. 2018; 50(10):1359-1365. PMC: 6168378. DOI: 10.1038/s41588-018-0203-z. View

19.

Abu-Libdeh B, Douiev L, Amro S, Shahrour M, Ta-Shma A, Miller C . Mutation in the COX4I1 gene is associated with short stature, poor weight gain and increased chromosomal breaks, simulating Fanconi anemia. Eur J Hum Genet. 2017; 25(10):1142-1146. PMC: 5602013. DOI: 10.1038/ejhg.2017.112. View

20.

Nagase H, Visse R, Murphy G . Structure and function of matrix metalloproteinases and TIMPs. Cardiovasc Res. 2006; 69(3):562-73. DOI: 10.1016/j.cardiores.2005.12.002. View