title: Association of TGFB1 29C/T and IL6 -572G/C polymorphisms with developmental hip dysplasia: a case-control study in adults with severe osteoarthritis.
abstract: OBJECTIVE
  Developmental dysplasia of the hip (DDH) increases the risk of severe adult hip osteoarthritis (OA). Transforming growth factor-β1 (TGF-beta1) and interleukin-6 (IL-6) are included in pathogenesis of OA, as well as in development of the musculoskeletal system. We investigated the association of single nucleotide polymorphisms (SNPs) known to reflect on the circulating levels of the two cytokines, specifically, 29 T → C transition in the TGFB1 signal sequence (rs1800470) and -572G → C transversion in the IL6 promoter (rs1800796), with DDH.
  
  
  METHODS
  We conducted a case-control study in consecutive unrelated adults with severe hip OA scheduled for total hip arthroplasty. Cases, patients with OA secondary to DDH (n = 68) and controls, patients with OA unrelated to DDH (n = 152) were genotyped at the two loci.
  
  
  RESULTS
  With adjustment for age, sex and genotype at the concurrent locus, cases were more likely (OR = 2.42, 95%CI 1.08-5.43; p = 0.032) to be transition homozygous at TGFB1 locus 29, and also more likely (OR = 6.36, 95%CI 2.57-15.7; p < 0.001) to be transversion homozygous at IL6 locus -572 than controls. Cases were also more likely (OR = 11.3, 95%CI 4.25-29.8; p < 0.001) than controls to carry one of the three genotypes combining transition/transversion homozygosity at both loci, or transition/transversion homozygosity at one and heterozygosity at the concurrent locus.
  
  
  CONCLUSIONS
  Data suggest association between TGFB1 29 T → C transition (rs1800470) and IL6 -572G → C transversion (rs1800796) with DDH, and also a possibility of TGF-beta1 and IL-6 interaction in DDH pathogenesis.
authors.affiliation: Department of Traumatology, University Hospital Centre Sestre milosrdnice, Vinogradska cesta 29, 10000, Zagreb, Croatia, cengict@me.com.
authors.forename: Tomislav
authors.initials: T
authors.lastname: Čengić
authors.forename: Vladimir
authors.initials: V
authors.lastname: Trkulja
authors.forename: Sandra Kraljević
authors.initials: SK
authors.lastname: Pavelić
authors.forename: Ivana
authors.initials: I
authors.lastname: Ratkaj
authors.forename: Elitza
authors.initials: E
authors.lastname: Markova-Car
authors.forename: Michele
authors.initials: M
authors.lastname: Mikolaučić
authors.forename: Robert
authors.initials: R
authors.lastname: Kolundžić
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019644:Arthroplasty, Replacement, Hip; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006618:Hip Dislocation, Congenital / Q000150:complications / Q000235:genetics* / Q000601:surgery; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015207:Osteoarthritis, Hip / Q000209:etiology / Q000235:genetics* / Q000601:surgery; D020641:Polymorphism, Single Nucleotide; D053773:Transforming Growth Factor beta1 / Q000235:genetics*; D055815:Young Adult
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1