title: PD-1 gene polymorphic variation is linked with first symptom of disease and severity of relapsing-remitting form of MS.
abstract: Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS), where inflammation, demyelination together with the axonopathy are the cardinal features on pathologic ground, with a combined genetic and environmental background. The associations of PD-1 single nucleotide polymorphisms (SNPs): PD-1.3 (in intron 4), PD-1.5 and PD-1.9 (both in exon 5) with clinical manifestation of MS in 479 south Polish individuals including 203 MS patients were analyzed. Presence of PD-1.5T allele was linked with the first manifestations of disease: diplopia and pyramidal signs - favored pyramidal signs but protected against of diplopia development. Farther, PD-1.3G/PD-1.5C/PD-1.9C haplotype significantly favored whereas GTC protected against diplopia. Besides, GTT haplotype strongly favored non-severe RRMS outcome and ATC haplotype was specific only for these MS patients. Our population-based case-control study, investigating selected three PD-1 SNPs: PD-1.3, PD-1.5 and PD-1.9, revealed that polymorphic variation may be rather disease-modifying than MS risk factor.
authors.affiliation: Department of Experimental Therapy, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, R. Weigl 12, 53-114 Wroclaw, Poland. Electronic address: epawlak@iitd.pan.wroc.pl.
authors.forename: Edyta
authors.initials: E
authors.lastname: Pawlak-Adamska
authors.affiliation: Department of Human Evolutionary Biology, Institute of Anthropology, Adam Mickiewicz University, Umultowska 89, 61-614 Poznan, Poland.
authors.forename: Oskar
authors.initials: O
authors.lastname: Nowak
authors.affiliation: Department of Experimental Therapy, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, R. Weigl 12, 53-114 Wroclaw, Poland.
authors.forename: Lidia
authors.initials: L
authors.lastname: Karabon
authors.affiliation: Department of Neurology, Wroclaw Medical University, Borowska 213, 50-566 Wroclaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Pokryszko-Dragan
authors.affiliation: Department of Experimental Therapy, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, R. Weigl 12, 53-114 Wroclaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Partyka
authors.affiliation: Department of Experimental Therapy, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, R. Weigl 12, 53-114 Wroclaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Tomkiewicz
authors.affiliation: Department of Clinical Biomechanics and Physiotherapy in Motor System Disorders, Faculty of Health Science, Wroclaw Medical University, Grunwaldzka 2, 50-355 Wroclaw, Poland.
authors.forename: Jakub
authors.initials: J
authors.lastname: Ptaszkowski
authors.affiliation: Department of Experimental Therapy, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, R. Weigl 12, 53-114 Wroclaw, Poland.
authors.forename: Irena
authors.initials: I
authors.lastname: Frydecka
authors.affiliation: Department of Neurology, Wroclaw Medical University, Borowska 213, 50-566 Wroclaw, Poland.
authors.forename: Ryszard
authors.initials: R
authors.lastname: Podemski
authors.affiliation: Department of Hematology, Blood Neoplastic Diseases, and Bone Marrow Transplantation, Medical University, Pasteura 4, 50-367 Wroclaw, Poland.
authors.forename: Jaroslaw
authors.initials: J
authors.lastname: Dybko
authors.affiliation: Department of Neurology, Wroclaw Medical University, Borowska 213, 50-566 Wroclaw, Poland.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Bilinska
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D004185:Disability Evaluation; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000235:genetics*; D011044:Poland; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics*; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor
keywords: Diplopia; Multiple sclerosis; PD-1 gene; PD-1.5; Pyramidal signs; RRMS