Polymorphisms in the tumor necrosis factor receptor genes affect the expression levels of membrane-bound type I and type II receptors.
The level of TNF receptors on various cells of immune system and its association with the gene polymorphism were investigated. Determining the levels of membrane-bound TNFα receptors on peripheral blood mononuclear cells (PBMCs) was performed by flow cytometry using BD QuantiBRITE calibration particles. Soluble TNF α receptor (sTNFRs) levels were determined by ELISA and genotyping was determined by PCR-RFLP. Homozygous TT individuals at SNP -609G/T TNFRI (rs4149570) showed lower levels of sTNFRI compared to GG genotype carriers. Homozygous carriers of CC genotype at SNP -1207G/C TNFRI (rs4149569) had lower expression densities of membrane-bound TNFRI on intact CD14(+) monocytes compared to individuals with the GC genotype. The frequency differences in the CD3(+) and CD19(+) cells expressing TNFRII in relation to SNP -1709A/T TNFRII (rs652625) in healthy individuals were also determined. The genotype CC in SNP -3609C/T TNFRII (rs590368) was associated with a lower percentage of CD14(+) cells expressing TNFRII compared to individuals with the CT genotype. Patients with rheumatoid arthritis had no significant changes in the frequencies of genotypes. Reduced frequency was identified for the combination TNFRI -609GT + TNFRII -3609CC only. The polymorphisms in genes represent one of cell type-specific mechanisms affecting the expression levels of membrane-bound TNF α receptors and TNF α -mediated signaling.
Laboratory of Molecular Immunology, Federal State Budgetary Institution "Research Institute of Clinical Immunology", Russian Academy of Medical Sciences Siberian Branch, 14, Yadrintsevskaya Street, Novosibirsk 630099, Russia.
Sergey V
SV
Sennikov
Laboratory of Molecular Immunology, Federal State Budgetary Institution "Research Institute of Clinical Immunology", Russian Academy of Medical Sciences Siberian Branch, 14, Yadrintsevskaya Street, Novosibirsk 630099, Russia.
Filipp F
FF
Vasilyev
Laboratory of Molecular Immunology, Federal State Budgetary Institution "Research Institute of Clinical Immunology", Russian Academy of Medical Sciences Siberian Branch, 14, Yadrintsevskaya Street, Novosibirsk 630099, Russia.
Julia A
JA
Lopatnikova
Laboratory of Molecular Immunology, Federal State Budgetary Institution "Research Institute of Clinical Immunology", Russian Academy of Medical Sciences Siberian Branch, 14, Yadrintsevskaya Street, Novosibirsk 630099, Russia.
Nadezhda S
NS
Shkaruba
Laboratory of Molecular Immunology, Federal State Budgetary Institution "Research Institute of Clinical Immunology", Russian Academy of Medical Sciences Siberian Branch, 14, Yadrintsevskaya Street, Novosibirsk 630099, Russia.
Alexander N
AN
Silkov
D000293:Adolescent; D000328:Adult; D000368:Aged; D018941:Antigens, CD19 / Q000378:metabolism; D017252:CD3 Complex / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism*; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000378:metabolism*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D055815:Young Adult
D018941:Antigens, CD19; D017252:CD3 Complex; D018950:Lipopolysaccharide Receptors; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha