title: Polymorphisms of the eNOS gene are associated with disease activity in rheumatoid arthritis.
abstract: Nitric oxide (NO) is a mediator in autoimmune responses and thus involved in the pathogenesis of a variety of rheumatic diseases. Genetic factors that influence the expression of the enzyme endothelial nitric oxide synthase (eNOS) that catalyzes NO synthesis are important for the control of NO level and consequently its activity. We have analyzed three functionally relevant polymorphisms of eNOS gene: T-786C, G894T and VNTR (4a/b), to investigate whether they are predisposing factors in pathogenesis of RA in Serbian population and to evaluate their role in clinical manifestations of RA. We performed genotyping of 196 patients with RA and the control group of 132 healthy individuals from Serbian population, using PCR and polymerase chain reaction-restriction fragment length polymorphism methods. Disease activity was prospectively assessed using number of tender joints, number of swollen joints and 28-joints disease activity score (DAS28). There were no differences between the patients and control groups in the genotypes and alleles frequencies of the three analyzed SNPs. Our results showed statistically significant differences in all three analyzed parameters of disease severity between 786TT/786CT and 786CC genotypes and between 894GG/894GT and 894TT genotypes. In the case of 4a/b polymorphism, carriers of minor allele had significantly lower DAS28 values. In conclusion, our results do not support the implication of analyzed eNOS gene polymorphisms in susceptibility to RA but associate them with the disease activity and give assumption that minor alleles are indicators of better clinical course.
authors.affiliation: Faculty of Medicine, Institute of Human Genetics, University of Belgrade, 26 Visegradska Str., Belgrade, 11000, Serbia.
authors.forename: Vera
authors.initials: V
authors.lastname: Bunjevacki
authors.affiliation: Faculty of Medicine, Institute of Human Genetics, University of Belgrade, 26 Visegradska Str., Belgrade, 11000, Serbia.
authors.forename: Nela
authors.initials: N
authors.lastname: Maksimovic
authors.affiliation: Faculty of Medicine, Institute of Human Genetics, University of Belgrade, 26 Visegradska Str., Belgrade, 11000, Serbia.
authors.forename: Biljana
authors.initials: B
authors.lastname: Jekic
authors.affiliation: Faculty of Medicine, Institute of Rheumatology, University of Belgrade, Resavska 69 Str., Belgrade, Serbia.
authors.forename: Vera
authors.initials: V
authors.lastname: Milic
authors.affiliation: Faculty of Medicine, Institute of Human Genetics, University of Belgrade, 26 Visegradska Str., Belgrade, 11000, Serbia.
authors.forename: Ljiljana
authors.initials: L
authors.lastname: Lukovic
authors.affiliation: Faculty of Medicine, Institute of Human Genetics, University of Belgrade, 26 Visegradska Str., Belgrade, 11000, Serbia.
authors.forename: Ivana
authors.initials: I
authors.lastname: Novakovic
authors.affiliation: Faculty of Medicine, Institute of Rheumatology, University of Belgrade, Resavska 69 Str., Belgrade, Serbia.
authors.forename: Nemanja
authors.initials: N
authors.lastname: Damjanov
authors.affiliation: Faculty of Medicine, Institute of Rheumatology, University of Belgrade, Resavska 69 Str., Belgrade, Serbia.
authors.forename: Goran
authors.initials: G
authors.lastname: Radunovic
authors.affiliation: Faculty of Medicine, Institute of Human Genetics, University of Belgrade, 26 Visegradska Str., Belgrade, 11000, Serbia. tatjanadamnjanovic@yahoo.com.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Damnjanovic
mesh_terms: D000368:Aged; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics*; D016022:Case-Control Studies; D004185:Disability Evaluation; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012307:Risk Factors; D055771:Serbia; D012720:Severity of Illness Index
chemical_list: C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III
keywords: Disease activity; Genetic polymorphisms; Rheumatoid arthritis; eNOS