title: A significant association exists between receptor tyrosine kinase-like orphan receptor 2 gene variants and the OPG/RANKL ratio in human plasma.
abstract: CONCLUSIONS
  There is a paucity of studies investigating association between ROR2 gene variants and osteoporosis and osteoarthritis-related phenotypes. The published literature suggests that osteoprotegerin (OPG) and receptor activator of nuclear factor-kB ligand (RANKL) are essential for bone metabolism and correlate with osteoarthritis manifestation and progression. The present study provides evidence of the significant association between ROR2 variants and the OPG/RANKL ratio in human plasma. The present results also suggest significant association between ROR2 polymorphisms and severity of radiographic hand osteoarthritis.
  
  
  BACKGROUND
  Despite the importance of the ROR-2 in skeletal physiology, there is a paucity of studies investigating the potential association of ROR2 gene variants with phenotypes relevant to osteoporosis and osteoarthritis. On the other hand, there is a considerable body of literature suggesting that OPG and RANKL and their ratio (OPG/RANKL) are essential for regulating bone resorption. This is also correlated with osteoarthritis manifestation and progression. The present study therefore examines whether ROR2 polymorphisms may be associated with the OPG/RANKL ratio and hand osteoarthritis (HOA).
  
  
  METHODS
  The study was conducted in a family-based sample of 1,515 Caucasian individuals, assessed for radiographic hand osteoarthritis, using the Kellgren/Lawrence score. Of these, 865 individuals were genotyped for 19 SNPs, relatively equally covering the ROR2 locus, and their plasma levels of OPG and RANKL were assayed. The association between the selected SNPs and OPG, along with the OPG/RANKL ratio and HOA, was explored using the pedigree disequilibrium test.
  
  
  RESULTS
  Of the total of 57 tests, 16 nominally significant results (p < 0.05) were obtained, which is considerably more than the three normally expected for type I error. The significant association signals for all three phenotypes were mapped to the intron 1 region. The most significant results were detected between OPG/RANKL and rs7048756 (p < 0.0005) and between adjacent rs4744107 and Kellgren/Lawrence score (p = 0.006).
  
  
  CONCLUSIONS
  The present study provides evidence of the significant association between ROR2 variants and the OPG/RANKL ratio in human plasma and also suggests ROR2 association with HOA.
authors: Human Population Biology Research Unit, Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors: S
authors: S
authors: Ermakov
authors: S
authors: S
authors: Trofimov
authors: I
authors: I
authors: Malkin
authors: G
authors: G
authors: Livshits
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D050823:Hand Joints / Q000000981:diagnostic imaging; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000097:blood / Q000000981:diagnostic imaging / Q000235:genetics*; D053244:Osteoprotegerin / Q000097:blood*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D053245:RANK Ligand / Q000097:blood*; D011859:Radiography; D057050:Receptor Tyrosine Kinase-like Orphan Receptors / Q000235:genetics*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D053244:Osteoprotegerin; D053245:RANK Ligand; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; D057050:Receptor Tyrosine Kinase-like Orphan Receptors