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



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.


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.


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.


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.

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This work has been supported by the Ministry of Education, Science and Sports of Croatia grants 335-0000000-3532 and 098-0000000-3530. The authors are grateful to Krešimir Crnogaća, MD, for assistance in X-ray analysis.

Conflict of interest

The authors declare that they have no conflict of interest.

Authors’ contributions

RK, VT and SKP conceived the study; RK, TC, SKP and VT defined the study protocol; RK, TC and MM recruited the patients and collected blood samples; SKP, IR, EMC performed genotyping; VT analysed the data; TC, VT, SKP and RK drafted the manuscript. All authors edited and approved the final version of the manuscript. RK coordinated and overlooked the entire project.


All procedures performed in the study involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. All patients gave an informed consent and the study was approved by the Local Ethics Committee (EP 7426/14-16).

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Correspondence to Tomislav Čengić or Robert Kolundžić.

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Tomislav Čengić, Vladimir Trkulja and Sandra Kraljević Pavelić contributed equally to this work.

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Čengić, T., Trkulja, V., Pavelić, S.K. et al. Association of TGFB1 29C/T and IL6 -572G/C polymorphisms with developmental hip dysplasia: a case–control study in adults with severe osteoarthritis. International Orthopaedics (SICOT) 39, 793–798 (2015).

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  • Developmental dysplasia of the hip
  • Hip osteoarthritis
  • TGFB1
  • IL6
  • Single nucleotide polymorphisms