Bone Morphogenetic Protein 6 Polymorphisms Are Associated with Radiographic Progression in Ankylosing Spondylitis

Abstract

Background and ObjectNearly 25 genetic loci associated with susceptibility to ankylosing spondylitis (AS) have been identified by several large studies. However, there have been limited studies to identify the genes associated with radiographic severity of the disease. Thus we investigated which genes involved in bone formation pathways might be associated with radiographic severity in AS.MethodsA total of 417 Korean AS patients were classified into two groups based on the radiographic severity as defined by the modified Stoke’ Ankylosing Spondylitis Spinal Score (mSASSS) system. Severe AS was defined by the presence of syndesmophytes and/or fusion in the lumbar or cervical spine (n = 195). Mild AS was defined by the absence of any syndesmophyte or fusion (n = 170). A total of 251 single nucleotide polymorphisms (SNPs) within 52 genes related to bone formation were selected and genotyped. Odds ratios (OR) and 95% confidence interval (95% CI) were analysed by multivariate logistic regression controlling for age at onset of symptoms, sex, disease duration, and smoking status as covariates.ResultsWe identified new loci of bone morphogenetic protein 6 (BMP6) associated with radiographic severity in patients with AS that passed false discovery rate threshold. Two SNPs in BMP6 were significantly associated with radiologic severity [rs270378 (OR 1.97, p = 6.74×10−4) and rs1235192 [OR 1.92, p = 1.17×10−3]) adjusted by covariates.ConclusionThis is the first study to demonstrate that BMP6 is associated with radiographic severity in AS, supporting the role wingless-type like/BMP pathway on radiographic progression in AS.

Association study of copy number variation in BMP8A gene with the risk of ankylosing spondylitis in Iranian population

“…47 On the other hand, BMP6 and 7 have recently been shown to be good indications to predict the progression of syndesmophyte development, especially in early stages. 26,46,48 In this study, despite the fact that the age and disease duration of the patients with syndesmophyte were higher than those without syndesmophyte, there was no relationship between BMP8A with demographic characteristics such as age, the age of disease onset or disease duration. But Park et al 41 reported the association of serum BMP7 elevation in AS patients with spinal fusion, subjects with old age, and high disease duration.…”

The Influence of Adalimumab and Cyclosporine A on the Expression Profile of the Genes Related to TGFβ Signaling Pathways in Keratinocyte Cells Treated with Lipopolysaccharide A

“…In turn, after 8 hours of HACAT incubation with the drug, we found overexpression of BMP2 and BMP6 (bone morphogenetic protein 2, 6) with simultaneous silencing of TGF β RIII expression; GDF5 (cartilage-derived morphogenetic protein 1) was involved in the differentiation of joint forming cells and interstitial spaces [ 66 ]. Chen et al and Joo et al emphasise, respectively, that the increase in the expression of BMP2 and BMP6 positively correlates with the severity of changes observed in ankylosing spondylitis [ 67 , 68 ]. In addition, studies by Chen et al indicated that the change in the expression profile of BMP2 resulted directly from the exposure of PBMCs to TNF- α [ 67 ].…”

Loss and gain of bone in spondyloarthritis: what drives these opposing clinical features?

“…Two SNPs in BMP6 (rs270378 and rs1235192) have been associated with increased risk of syndesmophyte formation with a stronger effect in patients with both SNPs suggesting that they confer the risk for syndesmophytes independently. 65 …”