title: VLA4 Gene Polymorphism and Susceptibility to Multiple Sclerosis in Slovaks.
abstract: Multiple sclerosis (MS) is an inflammatory autoimmune disease occurring in genetically sensitive individuals. As migration of immune cells into the CNS is facilitated by the Very Late Antigen 4 (VLA-4) integrin molecule, the VLA4 gene may be considered as a plausible candidate genetic risk factor for susceptibility to MS. Therefore, the objective of our study was to investigate the association between two genetic polymorphisms located in the VLA4 gene and the risk of multiple sclerosis. One hundred seventeen MS patients and 165 control subjects from Slovakia were genotyped for VLA4 gene SNP polymorphisms at positions 269 (C/A) and 3061 (A/G). The same study cohorts were also genotyped for the rs3135388 polymorphism tagging the HLA-DRB1*15:01 allele, which is a known genetic factor associated with susceptibility to develop MS in many populations. Our findings show for the first time that the rs3135388 polymorphism is a strong risk factor for MS in the Slovak population. Investigation of the VLA4 gene polymorphisms revealed a significantly higher frequency of the 3061AG genotype in MS patients compared to the controls (P ≤ 0.05). We suggest that the 3061AG polymorphic variant is an independent genetic risk factor for MS development in our population as it was significantly associated with this disease. The association was also confirmed after applying multivariate logistic-regression analysis adjusted for gender, age and HLA-DRB1*15:01 positivity as possible influencing factors.
authors.affiliation: Institute of Immunology, School of Medicine, Comenius University in Bratislava, Slovakia.
authors.forename: V
authors.initials: V
authors.lastname: Ďurmanová
authors.affiliation: Institute of Immunology, School of Medicine, Comenius University in Bratislava, Slovakia.
authors.forename: I
authors.initials: I
authors.lastname: Shawkatová
authors.affiliation: Institute of Immunology, School of Medicine, Comenius University in Bratislava, Slovakia.
authors.forename: J
authors.initials: J
authors.lastname: Javor
authors.affiliation: Institute of Immunology, School of Medicine, Comenius University in Bratislava, Slovakia.
authors.forename: Z
authors.initials: Z
authors.lastname: Párnická
authors.affiliation: 1st Department of Neurology, School of Medicine, Comenius University in Bratislava and University Hospital, Bratislava, Slovakia.
authors.forename: D
authors.initials: D
authors.lastname: Čopíková-Cundráková
authors.affiliation: 1st Department of Neurology, School of Medicine, Comenius University in Bratislava and University Hospital, Bratislava, Slovakia.
authors.forename: P
authors.initials: P
authors.lastname: Turčáni
authors.affiliation: 2nd Department of Neurology, School of Medicine, Comenius University in Bratislava and University Hospital, Bratislava, Slovakia.
authors.forename: I
authors.initials: I
authors.lastname: Lisá
authors.affiliation: Institute of Immunology, School of Medicine, Comenius University in Bratislava, Slovakia.
authors.forename: B
authors.initials: B
authors.lastname: Gajdošechová
authors.affiliation: Institute of Immunology, School of Medicine, Comenius University in Bratislava, Slovakia.
authors.forename: M
authors.initials: M
authors.lastname: Buc
authors.affiliation: Institute of Immunology, School of Medicine, Comenius University in Bratislava, Slovakia.
authors.forename: M
authors.initials: M
authors.lastname: Bucová
mesh_terms: D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D059811:HLA-DRB1 Chains / Q000235:genetics; D006801:Humans; D039041:Integrin alpha4beta1 / Q000235:genetics*; D008297:Male; D009103:Multiple Sclerosis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018154:Slovakia
chemical_list: D059811:HLA-DRB1 Chains; D039041:Integrin alpha4beta1