Association of interleukin-6 and transforming growth factor-β1 gene polymorphisms with developmental hip dysplasia and severe adult hip osteoarthritis: A preliminary study

Developmental hip dysplasia (DDH) greatly contributes to occurrence of severe hip osteoarthritis (OA) in adulthood, but the association between the two is not a perfect one. Both conditions are known to have a strong genetic component. Transforming growth factor β1 (TGF-β1) and interleukin-6 (IL-6) are two pro-inflammatory cytokines included in pathogenesis of OA, bone remodeling and development of bone and joint tissues. TGF-β1 gene has a polymorphic site in the signal sequence (29T → C) and “C allele carriage” is associated with higher circulating TGF-β1 levels. IL-6 gene has several polymorphic sites in the promoter region including −572T → C transition associated with higher circulating IL-6 levels. As a preliminary investigation on possible association between these polymorphisms and severe adult hip OA secondary to DDH, 28 consecutive patients and 20 healthy controls were genotyped at these loci. With adjustment for sex, “C allele carriage” in the TGF-β1 signal sequence and CC genotype (“transition homozygous”) at locus −572 in the IL-6 promoter were each associated with severe OA secondary to DDH (OR = 13.4, p = 0.016 and OR = 6.2, p = 0.024, respectively). The combination of these genotypes was particularly strongly associated with the disease (OR = 11.1, p < 0.001). Data support feasibility of larger-scale studies on potential association between TGF-β1 signal sequence and IL-6 promoter polymorphisms and occurrence of DDH and (un)related severe OA.