title: Functional Promoter Polymorphisms of MMP-2 C-735T and MMP-9 C-1562T and Their Synergism with MMP-7 A-181G in Multiple Sclerosis.
abstract: Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system. Matrix metalloproteinases (MMPs) play an important role in breakdown of blood-brain barrier, transmigration, and invasion of immune cells and formation of MS lesions. The aim of present study was to investigate the influence of MMP-2 C-735T and MMP-9 C-1562T variants and their synergism with MMP-7 A-181G on susceptibility to MS. In a case-control study 125 MS patients and 235 healthy individuals from Western Iran were investigated. The various genotypes of MMP-2, MMP-9, and MMP-7 were detected using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). In females the presence of MMP-2 C allele was associated with an increased risk of MS (OR = 1.69, p = 0.041). No significant difference was detected between the frequency of MMP-9 T allele in MS patients (8.2%) and controls (12.8%, p = 0.068). The concomitant presence of both MMP-2 C and MMP-7 G alleles was associated with 1.82-fold increased risk of MS (p = 0.002). Also, a synergism was detected between MMP-9 C and MMP-7 G alleles that elevated the risk of MS by 1.5-times (p = 0.035). The presence of haplotype MMP-9 T, MMP-7 G, and MMP-2 C (TGC) compared to haplotype CAG increased the risk of MS by 3.13-fold (p = 0.16). The present study suggests that gene-gene interactions and variants of more genes instead of single gene might play a role in susceptibility to MS. We indicated that synergism between variants of MMP-2, MMP-7, and MMP-9 genes might increase the risk of MS.
authors.affiliation: a Medical Biology Research Center , Kermanshah University of Medical Sciences , Kermanshah , Iran.|b Department of Biochemistry , Medical School, Kermanshah University of Medical Sciences , Kermanshah , Iran.
authors.forename: Zohreh
authors.initials: Z
authors.lastname: Rahimi
authors.affiliation: c Department of Biology , Science and Research Branch, Islamic Azad University , Tehran , Iran.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Abdan
authors.affiliation: a Medical Biology Research Center , Kermanshah University of Medical Sciences , Kermanshah , Iran.
authors.forename: Ziba
authors.initials: Z
authors.lastname: Rahimi
authors.affiliation: d Department of Neurology , Medical School, Kermanshah University of Medical Sciences , Kermanshah , Iran.
authors.forename: Nazanin
authors.initials: N
authors.lastname: Razazian
authors.affiliation: e Department of Biochemistry , Fars Science and Research Branch, Islamic Azad University , Fars , Iran.
authors.forename: Hadis
authors.initials: H
authors.lastname: Shiri
authors.affiliation: f Fertility and Infertility Research Center , Kermanshah University of Medical Sciences , Kermanshah , Iran.
authors.forename: Asad
authors.initials: A
authors.lastname: Vaisi-Raygani
authors.affiliation: b Department of Biochemistry , Medical School, Kermanshah University of Medical Sciences , Kermanshah , Iran.
authors.forename: Ebrahim
authors.initials: E
authors.lastname: Shakiba
authors.affiliation: e Department of Biochemistry , Fars Science and Research Branch, Islamic Azad University , Fars , Iran.
authors.forename: Mahmood
authors.initials: M
authors.lastname: Vessal
authors.affiliation: f Fertility and Infertility Research Center , Kermanshah University of Medical Sciences , Kermanshah , Iran.
authors.forename: Mohammad-Taher
authors.initials: MT
authors.lastname: Moradi
mesh_terms: D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D004843:Epistasis, Genetic; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007492:Iran; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics* / Q000378:metabolism; D020783:Matrix Metalloproteinase 7 / Q000235:genetics* / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics* / Q000378:metabolism; D009103:Multiple Sclerosis / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012150:Polymorphism, Restriction Fragment Length; D011401:Promoter Regions, Genetic; D012306:Risk
chemical_list: C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: Haplotype; MMP-2 C-735T; MMP-7 A-181G; MMP-9 C-1562T; multiple sclerosis