Association of TGFB1 29C/T and IL6-572G/C polymorphisms with developmental hip dysplasia: a case-control study in adults with severe osteoarthritis

Purpose Developmental dysplasia of the hip (DDH) increases the risk of severe adult hip osteoarthritis (OA). Transforming growth factor-beta 1 (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 -> aEuro parts per thousand C transition in the TGFB1 signal sequence (rs1800470) and -572G -> aEuro parts per thousand 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 -> aEuro parts per thousand C transition (rs1800470) and IL6 -572G -> aEuro parts per thousand C transversion (rs1800796) with DDH, and also a possibility of TGF-beta1 and IL-6 interaction in DDH pathogenesis.