title: Genetic determinants of circulating levels of tumor necrosis factor receptor II and their association with TNF-RII gene polymorphisms.
abstract: BACKGROUND
  Tumor necrosis factor alpha (TNFalpha) is a cytokine involved in inflammatory, immune, and metabolic events. TNFalpha signals are mediated through activation of two receptors, one of which is tumor necrosis factor receptor TNF-RII.
  
  
  OBJECTIVE
  To examine the effects of genetic and environmental factors on TNF-RII plasma concentration and its association with polymorphisms in the TNF-RII gene locus.
  
  
  METHODS
  The levels of sTNF-RII were determined in 897 individuals. The association between sTNF-RII and polymorphisms in its structural gene locus was examined by pedigree-based association analyses (PDT) and transmission disequilibrium tests (TDTs).
  
  
  RESULTS
  49.57% of the adjusted sTNF-RII variability was attributable to genetic factors. sTNF-RII plasma levels were nominally associated with the genomic region spanning TNF-RII promoter and the first intron, represented by rs976881 (p=0.029). Although after correction for multiple testing this PDT signal formally did not reach statistical significance, it was reflected also in series of TDTs and further confirmed by association observed for haplotype of rs976881 with rs590368 (nominal p=0.006) and by ANOVA.
  
  
  CONCLUSIONS
  sTNF-RII plasma concentration is determined by both genetic and environmental factors. Our results suggest association between sTNF-RII levels and polymorphisms in vicinity to TNF-RII promoter region. This finding requires further thorough validation in other populations.
authors.affiliation: Human Population Biology Research Unit, Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Yulia
authors.initials: Y
authors.lastname: Vistoropsky
authors.forename: Sergey
authors.initials: S
authors.lastname: Ermakov
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Toliat
authors.forename: Svetlana
authors.initials: S
authors.lastname: Trofimov
authors.forename: Janine
authors.initials: J
authors.lastname: Altmüller
authors.forename: Ida
authors.initials: I
authors.lastname: Malkin
authors.forename: Peter
authors.initials: P
authors.lastname: Nürnberg
authors.forename: Gregory
authors.initials: G
authors.lastname: Livshits
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002877:Chromosomes, Human / Q000235:genetics; D005260:Female; D005819:Genetic Markers; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood* / Q000235:genetics*; D055815:Young Adult
chemical_list: D005819:Genetic Markers; D047889:Receptors, Tumor Necrosis Factor, Type II