Association of MMP-2 (–1306 C/T) Gene Polymorphism with Predisposition to Optic Neuritis and Optic Neuritis Together with Multiple Sclerosis
Abstract
1. Introduction
2. Materials and Methods
Statistical Analysis
3. Results
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Acknowledgments
Conflicts of Interest
References
- Dooley, M.C.; Foroozan, R. Optic neuritis. J. Ophthalmic Vis. Res. 2010, 5, 182–187. [Google Scholar] [PubMed]
- Achiron, A.; Barak, Y. Multiple sclerosis from probable to definite diagnosis: A 7-year prospective study. Arch. Neurol. 2000, 57, 974–979. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Horton, S.; MacDonald, D.J.; Erickson, K.M.S. Exercise, and the potential for older adults. Eur. Rev. Aging Phys. Act. 2010, 7, 49–57. [Google Scholar] [CrossRef]
- Voss, E.; Raab, P.; Trebst, C.; Stangel, M. Clinical approach to optic neuritis: Pitfalls, red flags and differential diagnosis. Ther. Adv. Neurol. Disord. 2011, 4, 123–134. [Google Scholar] [CrossRef] [PubMed]
- Kaushik, M.; Wang, C.Y.; Barnett, M.H.; Garrick, R.; Parratt, J.; Graham, S.L.; Sriram, P.; Yiannikas, C.; Klistorner, A. Inner nuclear layer thickening is inversley proportional to retinal ganglion cell loss in optic neuritis. PLoS ONE 2013, 8, e78341. [Google Scholar] [CrossRef] [PubMed]
- Halliday, A.M.; McDonald, W.I. Pathophysiology of demyelinating disease. Br. Med. Bull. 1977, 33, 21. [Google Scholar] [CrossRef] [PubMed]
- Hoorbakht, H.; Bagherkashi, F. Optic Neuritis, its Differential Diagnosis and Management. Open Ophthalmol. J. 2012, 6, 65–72. [Google Scholar] [CrossRef] [PubMed]
- Tasaki, A.; Shimizu, F.; Sano, Y.; Fujisawa, M.; Takahashi, T.; Haruki, H.; Abe, M.; Koga, M.; Kanda, T. Autocrine MMP-2/9 secretion increases the BBB permeability in neuromyelitis optica. J. Neurol. Neurosurg. Psychiatry 2014, 85, 419–430. [Google Scholar] [CrossRef] [PubMed]
- Gašparovic, I.; Čizmarević, N.S.; Lovrečić, L.; Perković, O.; Lavtar, P.; Jazbec, S.Š.; Kapović, M.; Peterlin, B.; Ristić, S. MMP-2 -1575G/A polymorphism modifies the onset of optic neuritis as a first presenting symptom in MS? J. Neuroimmunol. 2015, 286, 13–15. [Google Scholar] [CrossRef] [PubMed]
- Engelhardt, B. T cell migration into the central nervous system during health and disease: Different molecular keys allow access to different central nervous system compartments. Clin. Exp. Neuroimmunol. 2010, 1, 79–93. [Google Scholar] [CrossRef]
- Fingleton, B.M.; Heppner Goss, K.J.; Crawford, H.C.; Matrisian, L.M. Matrilysin in early stage intestinal tumorigenesis. APMIS 1999, 107, 102–110. [Google Scholar] [CrossRef] [PubMed]
- Stamenkovic, I. Matrix metalloproteinases in tumor invasion and metastasis. Semin. Cancer Biol. 2000, 10, 415–433. [Google Scholar] [CrossRef] [PubMed]
- Chakraborti, S.; Mandal, M.; Das, S.; Mandal, A.; Chakraborti, T. Regulation of matrix metalloproteinases an overview. Mol. Cell. Biochem. 2003, 253, 269–285. [Google Scholar] [CrossRef] [PubMed]
- Nagase, H.; Woessner, J.F. Matrix metalloproteinases. J. Biol. Chem. 1999, 274, 21491–21494. [Google Scholar] [CrossRef] [PubMed]
- Johansson, N.; Ahonen, M.; Kahari, V.M. Matrix metalloproteinases in tumor invasion. Cell. Mol. Life Sci. 2000, 57, 5–15. [Google Scholar] [CrossRef] [PubMed]
- Curran, S.; Murray, G.I. Matrix metalloproteinases in tumour invasion and metastasis. J. Pathol. 1999, 189, 300–308. [Google Scholar] [CrossRef]
- Kahari, V.M.; Saarialho-Kere, U. Matrix metalloproteinases and their inhibitors in tumour growth and invasion. Ann. Med. 1999, 31, 34–45. [Google Scholar] [CrossRef] [PubMed]
- Westermarck, J.; Kähäri, V.M. Regulation of matrix metalloproteinase expression in tumor invasion. FASEB J. 1999, 13, 781–792. [Google Scholar] [CrossRef] [PubMed]
- Egeblad, M.; Werb, Z. New functions for the matrix metalloproteinases in cancer progression. Nat. Rev. Cancer 2002, 2, 161–174. [Google Scholar] [CrossRef] [PubMed]
- McCaswley, L.J.; Matrisian, L.M. Matrix metalloproteinases: They’re not just for matrix anymore! Curr. Opin. Cell. Biol. 2001, 13, 534–540. [Google Scholar] [CrossRef]
- De Groef, L.; Van Hove, I.; Dekeyster, E.; Stalmans, I.; Moons, L. MMPs in the neuroretina and optic nerve: Modulators of glaucoma pathogenesis and repair? Investig. Ophthalmol. Vis. Sci. 2014, 55, 1953–1964. [Google Scholar] [CrossRef] [PubMed]
- Hosokawa, T.; Nakajima, H.; Doi, Y.; Sugino, M.; Kimura, F.; Hanafusa, T.; Takahashi, T. Increased serum matrix metalloproteinase-9 in neuromyelitis optica: Implication of disruption of blood–brain barrier. J. Neuroimmunol. 2011, 236, 81–86. [Google Scholar] [CrossRef] [PubMed]
- Ye, S. Polymorphism in matrix metalloproteinase gene promoters: Implication in regulation of gene expression and susceptibility of various diseases. Matrix Biol. 2000, 19, 623. [Google Scholar] [CrossRef]
- Price, S.J.; Greaves, D.R.; Watkins, H. Identification of novel, functional genetic variants in the human matrix metalloproteinases-2 gene: Role of SP1 in allele-specific transcriptional regulation. J. Biol. Chem. 2001, 276, 7549–7558. [Google Scholar] [CrossRef] [PubMed]
- Vasku, V.; Vasku, A.; Tschoplova, S.; Izakovicova, H.L.; Semradova, V.; Vácha, J. Genotype association of C(-735)T polymorphism in matrix metalloproteinase 2 gene with G(8002)A endothelin 1 gene with plaque psoriasis. Dermatology 2002, 204, 262–265. [Google Scholar] [CrossRef] [PubMed]
- Shams, P.N.; Plant, G.T. Optic neuritis: A review. Int. MS J. 2009, 16, 82–89. [Google Scholar] [PubMed]
- Li, J.; Tripathi, R.C.; Tripathi, B.J. Drug-induced ocular disorders. Drug Saf. 2008, 31, 127–141. [Google Scholar] [CrossRef] [PubMed]
- McDonald, W.I.; Compston, A.; Edan, G.; Goodkin, D.; Hartung, H.P.; Lublin, F.D.; McFarland, H.F.; Paty, D.W.; Polman, C.H.; Reingold, S.C.; et al. Recommended diagnostic criteria for multiple sclerosis: Guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann. Neurol. 2001, 50, 121–127. [Google Scholar] [CrossRef] [PubMed]
- Swanton, J.K.; Fernando, K.; Dalton, C.M.; Miszkiel, K.A.; Thompson, A.J.; Plant, G.T.; Miller, D.H. Modification of MRI criteria for multiple sclerosis in patients with clinically isolated syndromes. J. Neurol. Neurosurg. Psychiatry 2006, 77, 830–833. [Google Scholar] [CrossRef] [PubMed]
- Swanton, J.K.; Rovira, A.; Tintore, M.; Altmann, D.R.; Barkhof, F.; Filippi, M.; Huerga, E.; Miszkiel, K.A.; Plant, G.T.; Polman, C.; et al. MRI criteria for multiple sclerosis in patients presenting with clinically isolated syndromes: A multicentre retrospective study. Lancet Neurol. 2007, 6, 677–686. [Google Scholar] [CrossRef]
- Hannocks, M.J.; Zhang, X.; Gerwien, H.; Chashchina, A.; Burmeister, M.; Korpos, E.; Song, J.; Sorokin, L. The gelatinases, MMP-2 and MMP-9, as fine tuners of neuroinflammatory processes. Matrix Biol. 2017, 21, 30334–30337. [Google Scholar] [CrossRef] [PubMed]
- Optic Neuritis Study Group. The clinical profile of optic neuritis. Experience of the optic neuritis treatment trial. Arch. Ophthalmol. 1991, 109, 1673–1688. [Google Scholar]
- Rosenberg, G.A. Matrix metalloproteinases in neuroinflammation. Glia 2002, 39, 279–291. [Google Scholar] [CrossRef] [PubMed]
- Goverman, J. Autoimmune T cell responses in the central nervous system. Nat. Rev. Immunol. 2009, 9, 393–407. [Google Scholar] [CrossRef] [PubMed]
- Gerwien, H.; Hermann, S.; Zhang, X.; Korpos, E.; Song, J.; Kopka, K.; Faust, A.; Wenning, C.; Gross, C.C.; Honold, L.; et al. Imaging matrix metalloproteinase activity in multiple sclerosis as a specific marker of leukocyte penetration of the blood-brain barrier. Sci. Transl. Med. 2016, 8, 364ra152. [Google Scholar] [CrossRef] [PubMed]
- Gurney, K.J.; Estrada, E.Y.; Rosenberg, G.A. Blood–brain barrier disruption by stromelysin-1 facilitates neutrophil infiltration in neuroinflammation. Neurobiol. Dis. 2006, 23, 87–96. [Google Scholar] [CrossRef] [PubMed]
- Rosenberg, G.A.; Estrada, E.Y.; Dencoff, J.E.; Stetler-Stevenson, W.G. Tumor necrosis factor-α-induced gelatinase B causes delayed opening of the blood-brain barrier: An expanded therapeutic window. Brain Res. 1995, 703, 151–155. [Google Scholar] [CrossRef]
- Rosenberg, G.A.; Kornfeld, M.; Estrada, E.; Kelley, R.O.; Liotta, L.A.; Stetler-Stevenson, W.G. TIMP-2 reduces proteolytic opening of blood-brain barrier by type IV collagenase. Brain Res. 1992, 576, 203–207. [Google Scholar] [CrossRef]
- Chandler, S.M.K.M.; Miller, K.M.; Clements, J.M.; Lury, J.; Corkill, D.; Anthony, D.C.C.; Adams, S.E.; Gearing, A.J.H. Matrix metalloproteinases, tumor necrosis factor and multiple sclerosis: An overview. J. Neuroimmunol. 1997, 72, 155–161. [Google Scholar] [CrossRef]
- Galboiz, Y.; Shapiro, S.; Lahat, N.; Rawashdeh, H.; Miller, A. Matrix metalloproteinases and their tissue inhibitors as markers of disease subtype and response to interferon-beta therapy in relapsing and secondary-progressive multiple sclerosis patients. Ann. Neurol. 2001, 50, 443–451. [Google Scholar] [CrossRef] [PubMed]
- Anthony, D.C.; Ferguson, B.; Matyzak, M.K.; Miller, K.M.; Esiri, M.M.; Perry, V.H. Differential matrix metalloproteinase expression in cases of multiple sclerosis and stroke. Neuropathol. Appl. Neurobiol. 1997, 23, 406–415. [Google Scholar] [CrossRef] [PubMed]
- Bar-Or, A.; Nuttall, R.K.; Duddy, M.; Alter, A.; Kim, H.J.; Ifergan, I.; Pennington, C.J.; Bourgoin, P.; Edwards, D.R.; Yong, V.W. Analyses of all matrix metalloproteinase members in leukocytes emphasize monocytes as major inflammatory mediators in multiple sclerosis. Brain 2003, 126, 2738–2749. [Google Scholar] [CrossRef] [PubMed]
- Walker, E.J.; Rosenberg, G.A. Divergent role for MMP-2 in myelin breakdown and oligodendrocyte death following transient global ischemia. J. Neurosci. Res. 2010, 88, 764–773. [Google Scholar] [CrossRef] [PubMed]
- Maeda, A.; Sobel, R.A. Matrix metalloproteinases in the normal human central nervous system, microglial nodules, and multiple sclerosis lesions. J. Neuropathol. Exp. Neurol. 1996, 55, 300–309. [Google Scholar] [CrossRef] [PubMed]
- Van Horssen, J.; Vos, C.M.; Admiraal, L.; Montagne, L.; van der Valk, P.; de Vries, H.E. Matrix metalloproteinase-19 is highly expressed in active multiple sclerosis lesions. Neuropathol. Appl. Neurobiol. 2006, 32, 585–593. [Google Scholar] [CrossRef] [PubMed]
- Aksoy, D.; Ateş, Ö.; Kurt, S.; Çevik, B.; Sümbül, O. Analysis of MMP2-1306C/T and TIMP2G-418C polymorphisms with relapsing remitting multiple sclerosis. J. Investig. Med. 2016, 64, 1143–1147. [Google Scholar] [CrossRef] [PubMed]
- Modvig, S.; Degn, M.; Horwitz, H. Relationship between cerebrospinal fluid biomarkers for inflammation, demyelination and neurodegeneration in acute optic neuritis. PLoS ONE 2013, 8, e77163. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Soderstrom, M. The clinical and paraclinical profile of optic neuritis: A prospective study. Ital. J. Neurol. Sci. 1995, 16, 167–176. [Google Scholar] [CrossRef] [PubMed]
- Feldman, A.; Gurevich, M.; Huna-Baron, R.; Achiron, A. The role of B cells in the early onset of the first demyelinating event of acute optic neuritis. Investig. Ophthalmol. Vis. Sci. 2015, 56, 1349–1356. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Kelly, M.A.; Cavan, D.A.; Penny, M.A.; Mijovic, C.H.; Jenkins, D.; Morrissey, S.; Miller, D.H.; Barnett, A.H.; Francis, D.A. The influence of HLA-DR and -DQ alleles on progression to multiple sclerosis following a clinically isolated syndrome. Hum. Immunol. 1993, 37, 185–191. [Google Scholar] [CrossRef]
- Lucchinetti, C.F.; Kiers, L.; O’duffy, A.; Gomez, M.R.; Cross, S.; Leavitt, J.A.; O’brien, P.; Rodriguez, M. Risk factors for developing multiple sclerosis after childhood optic neuritis. Neurology 1997, 49, 1413–1418. [Google Scholar] [CrossRef] [PubMed]
- Frederiksen, J.L.; Madsen, H.O.; Ryder, L.P.; Larsson, H.B.; Morling, N.; Svejgaard, A. HLA typing in acute optic neuritis. Arch. Neurol. 1997, 54, 76–80. [Google Scholar] [CrossRef] [PubMed]
- Francis, D.A.; Compston, D.A.S.; Batchelor, J.R.; McDonald, W.I. A reassessment of the risk of multiple sclerosis developing in patients with optic neuritis after extended follow-up. J. Neurol. Neurosurg. Psychiatry 1987, 50, 758–765. [Google Scholar] [CrossRef] [PubMed]
- Caillier, S.J.; Briggs, F.; Cree, B.A.; Baranzini, S.E.; Fernandez-Viña, M.; Ramsay, P.P.; Khan, O.; Royal, W.; Hauser, S.L.; Barcellos, L.F.; et al. Uncoupling the roles of HLA-DRB1 and HLA-DRB5 genes in multiple sclerosis. J. Immunol. 2008, 181, 5473–5480. [Google Scholar] [CrossRef] [PubMed]
- Tang, W.M.; Pulido, J.S.; Eckles, D.D.; Han, D.P.; Mieler, W.F.; Pierce, K. The association of HLA-DR15 and intermediate uveitis. Am. J. Ophthalmol. 1997, 123, 70–75. [Google Scholar] [CrossRef]
Symptoms | Typical ON |
---|---|
Age | Young patient <50 years |
Visual acuity loss time | Acute/subacute visual acuity loss |
Visual acuity loss progression | Visual acuity loss progressing for few days or few weeks |
Damage | Mostly one eye |
Visual acuity | ↓ in 90% of cases |
Visual field | Changes noticed in 97% of cases |
Color vision | In acute period, blue-yellow color vision loss; in subacute period, red-green color vision loss |
Visual evoked potentials (VEP) | ↓ VEP latency |
Optical coherent tomography (OCT) | Optic nerve disc edema (mostly in superior and nasal quadrants), noticed in 20% of patients |
Pain | Acute painful visual acuity loss, especially ↑ with eye movement |
Optic nerve disc | Mostly normal optic nerve disc |
Vitreous | Normal |
Orbit | Normal |
Anamnesis | ON in anamnesis or MS in anamnesis. Patients without MS had MS-like lesions but were not followed up after ON treatment in our study, only redirected for neurological follow-up. |
Neurological symptoms | Neurological symptoms, allowing to suspect MS |
Treatment effect using steroids | Shortens the duration of the disease |
Improvement | Spontaneous improvement in 2–3 weeks |
Prognosis | Mostly good |
Recurrence (5–10 years) | 28% |
DIS Can Be Demonstrated by ≥1 T2 Lesion a in at Least 2 of 4 Areas of the CNS: |
---|
Periventricular |
Juxtacortical |
Infratentorial |
Spinal cord b |
Characteristic | ON Group n = 62 | Control Group n = 318 | p |
---|---|---|---|
Gender, n (%) | |||
Males | 21 (31.7) | 113 (35.5) | 0.462 * |
Females | 41 (66.1) | 205 (33.9) | |
Age, median (IQR), years | 34 (17) | 36 (16) | 0.294 ** |
With MS, n (%) | 26 (41.9) | NA | … |
Without MS, n (%) | 36 (58.1) | NA | … |
Changes in visual evoked potential (VEP), n | 62 | NA | … |
Pain, n | 62 | NA | … |
Exophthalmus, n | 1 | NA | … |
Decreased visual acuity, n | 62 | NA | … |
Laterality, n | |||
Unilateral | 61 | NA | … |
Bilateral | 1 | ||
Decreased color vision, n | 62 | NA | … |
Treatment with intravenous solumedrol and later per oral prednisolone, n | 62 | NA | … |
Visual acuity (affected eye), median (IQR) | |||
Before treatment | 0.2 (0.58) | NA | <0.001 *** |
After treatment | 0.8 (0.70) | NA | |
Farnsworth-Munsell 100 hue test score, median (IQR) | 90 (29.50) | 57 (31.50) | 0.004 **** |
Optic nerve disc appearance | |||
Normal | 57 | NA | … |
Swelling | 5 | ||
Retinal nerve fiber layer thickness, median (IQR), μM | |||
Superior | 146 (55.5) | 130.5 (14.0) | 0.058 ** |
Temporal | 65 (36.0) | 67 (14) | 0.762 ** |
Inferior | 144 (61.0) | 137 (21.25) | 0.165 ** |
Nasal | 91 (60.0) | 90 (19.0) | 0.323 ** |
C-reactive protein, mg/L | <4 | NA | … |
Gene Marker | Genotype/Allele | Control Group n (%) (n = 318) | p HWE | ON Group n (%) (n = 62) | p HWE | p Value |
---|---|---|---|---|---|---|
MMP-2(-1306 C/T)rs243865 | Genotype | |||||
C/C | 190 (59.75) | 0.382 | 44 (71.00) | 0.181 | χ2 = 5.340 | |
C/T | 108 (33.96) | 18 (29.00) | p = 0.069 | |||
T/T | 20 (6.29) | 0 (0.00) | ||||
Total | 318 (100.00) | 62 (100) | ||||
Allele | ||||||
C | 488 (76.70) | 106 (85.50) | 0.031 | |||
T | 148 (23.30) | 18 (14.50) |
Model | Genotype/Allele | OR (95% CI) | p | AIC |
---|---|---|---|---|
Co dominant | C/C | 1 | 333.562 | |
C/T | 0.720 (0.396–1.308) | 0.280 | ||
T/T | 0 | 0.998 | ||
Dominant | C/T + T/T vs. C/C | 0.607 (0.336–1.098) | 0.099 | 337.252 |
Recessive | T/T vs. C/C + C/T | 0 | 0.998 | 332.763 |
Overdominant | C/T vs. T/T + C/C | 0.648 (0.305–1.375) | 0.259 | 339.521 |
Additive | T | 0.566 (0.333–0.962) | 0.036 | 335.184 |
Gene Marker | Genotype/Allele | Control Group n (%)(n = 318) | ON Group without MS (%)(n = 36) | p | Control Group n (%) (n = 318) | ON Group with MSn (%) (n = 26) | p |
---|---|---|---|---|---|---|---|
MMP-2(-1306 C/T)rs243865 | Genotype | 190 (59.75) | 190 (59.75) | 19 (73.10) | |||
C/C | 108 (33.96) | 25 (69.40) | 0.23 | 108 (33.96) | 7 (26.90) | 0.26 | |
C/T | 20 (6.29) | 11 (30.60) | 7 | 20 (6.29) | 0 (0.00) | 0 | |
T/T | 318 (100.00) | 0 (0.00) | 318 (100.00) | 26 (100.00) | |||
Total | 36 (100.00) | ||||||
Allele | 488 (76.70) | 488 (76.70) | 45 (86.54) | ||||
C | 148 (23.30) | 61 (84.70) | 0.12 | 148 (23.30) | 7 (13.46) | 0.10 | |
T | 11 (15.30) | 3 | 4 |
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Liutkevičienė, R.; Vilkevičiūtė, A.; Banevičus, M.; Miežytė, R.; Kriaučiūnienė, L. Association of MMP-2 (–1306 C/T) Gene Polymorphism with Predisposition to Optic Neuritis and Optic Neuritis Together with Multiple Sclerosis. Medicina 2018, 54, 29. https://doi.org/10.3390/medicina54020029
Liutkevičienė R, Vilkevičiūtė A, Banevičus M, Miežytė R, Kriaučiūnienė L. Association of MMP-2 (–1306 C/T) Gene Polymorphism with Predisposition to Optic Neuritis and Optic Neuritis Together with Multiple Sclerosis. Medicina. 2018; 54(2):29. https://doi.org/10.3390/medicina54020029
Chicago/Turabian StyleLiutkevičienė, Rasa, Alvita Vilkevičiūtė, Mantas Banevičus, Raminta Miežytė, and Loresa Kriaučiūnienė. 2018. "Association of MMP-2 (–1306 C/T) Gene Polymorphism with Predisposition to Optic Neuritis and Optic Neuritis Together with Multiple Sclerosis" Medicina 54, no. 2: 29. https://doi.org/10.3390/medicina54020029
APA StyleLiutkevičienė, R., Vilkevičiūtė, A., Banevičus, M., Miežytė, R., & Kriaučiūnienė, L. (2018). Association of MMP-2 (–1306 C/T) Gene Polymorphism with Predisposition to Optic Neuritis and Optic Neuritis Together with Multiple Sclerosis. Medicina, 54(2), 29. https://doi.org/10.3390/medicina54020029