title: Association of Pre-miRNA-499 rs3746444 and Pre-miRNA-146a rs2910164 Polymorphisms and Susceptibility to Behcet's Disease.
abstract: MiRNAs and NFKB1 are well-known immune response and inflammation regulators. MiRNA gene polymorphisms may affect miRNA biogenesis and function and, may thus, lead to changes in the expression of hundreds of genes such as NFKB1. The aim of this study was to investigate the association of Behcet's disease (BD) with NFKB1 rs28362491, pre-miRNA-146a rs2910164, and pre-miRNA-499 rs3746444 polymorphisms, as well as the analysis of their single and combined effects on its susceptibility in a Turkish population. These polymorphisms were analyzed by using the polymerase chain reaction-restriction fragment length polymorphism method in 100 BD patients and 145 healthy control subjects. The results were analyzed statistically using Pearson chi-square (χ(2)) test and Fisher's exact test (two sided). According to genotype analysis, the frequencies of ins/ins genotype and ins allele of rs28362491 were considerably higher in BD patients. Also, miRNA-499 rs3746444 homozygous (TT) genotypes exibited a significantly higher risk in patients with BD (odds ratios [OR]=3.0, 95% confidence intervals [95% CI]=1.284-7.007, p=0.017). Moreover, the frequency of T allele of rs3746444 was a risk factor for BD (OR=1.562, 95% CI=1.087-2.24, p=0.015). In addition, significant differences were found between the groups concerning miRNA-146a rs2910164 polymorphism. Homozygous CC genotype and C allele of rs2910164 polymorphism were found to be protective factors against BD. The results of the combined genotype analysis showed no notable differences between the multiple comparisons of rs28362491-rs2910164 and of rs28362491-rs3746444 in patients and control groups. Our data demonstrate that homozygous CC genotype and C allele of rs2910164 polymorphism are protective factors against BD, but rs3746444 and rs28362491 polymorphisms in miRNA-499 and in NFKB1 promoter are involved in the genetic susceptibility of BD. In addition, TT and ins/ins genotypes may influence certain proinflammatory cytokines and, may thus, play a role in the pathogenesis of BD.
authors.affiliation: 1 Department of Medical Biology, Cerrahpasa Medical Faculty, Istanbul University , Istanbul, Turkey .
authors.forename: Tuba
authors.initials: T
authors.lastname: Oner
authors.affiliation: 1 Department of Medical Biology, Cerrahpasa Medical Faculty, Istanbul University , Istanbul, Turkey .
authors.forename: Guven
authors.initials: G
authors.lastname: Yenmis
authors.affiliation: 1 Department of Medical Biology, Cerrahpasa Medical Faculty, Istanbul University , Istanbul, Turkey .
authors.forename: Kubra
authors.initials: K
authors.lastname: Tombulturk
authors.affiliation: 1 Department of Medical Biology, Cerrahpasa Medical Faculty, Istanbul University , Istanbul, Turkey .
authors.forename: Cansu
authors.initials: C
authors.lastname: Cam
authors.affiliation: 2 Department of Dermatological and Venereal Diseases, Bezmialem Medical Faculty, Bezmialem University , Istanbul, Turkey .
authors.forename: Ozlem Su
authors.initials: OS
authors.lastname: Kucuk
authors.affiliation: 3 Department of Molecular Biology and Genetics, Faculty of Arts and Sciences, Acibadem University , Istanbul, Turkey .
authors.forename: Mustafa Cengiz
authors.initials: MC
authors.lastname: Yakicier
authors.affiliation: 2 Department of Dermatological and Venereal Diseases, Bezmialem Medical Faculty, Bezmialem University , Istanbul, Turkey .
authors.forename: Didem
authors.initials: D
authors.lastname: Dizman
authors.affiliation: 1 Department of Medical Biology, Cerrahpasa Medical Faculty, Istanbul University , Istanbul, Turkey .
authors.forename: Gonul Kanıgur
authors.initials: GK
authors.lastname: Sultuybek
mesh_terms: D000328:Adult; D001528:Behcet Syndrome / Q000097:blood / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D052002:NF-kappa B p50 Subunit / Q000097:blood / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: C542542:MIRN146 microRNA, human; C548683:MIRN499 microRNA, human; D035683:MicroRNAs; D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human