title: Transforming growth factor β 869C/T and interleukin 6 -174G/C polymorphisms relate to the severity and progression of bone-erosive damage detected by ultrasound in rheumatoid arthritis.
abstract: BACKGROUND
  Single nucleotide polymorphisms (SNPs) of transforming growth factor β (TGF-β) and IL-6 genes (respectively, 869C/T and -174G/C) have been associated with radiographic severity of bone-erosive damage in patients with rheumatoid arthritis (RA). Musculoskeletal ultrasound (US) is more sensitive than radiography in detecting bone erosion. We analyzed the association between TGF-β 869C/T and IL-6 -174G/C SNPs and bone-erosive damage, evaluated by US, in a cohort of patients with severely active RA.
  
  
  METHODS
  Seventy-seven patients were enrolled before beginning anti-TNF treatment. Disease activity was measured using the disease activity score in 28 joints, and the clinical response was evaluated according to the European League Against Rheumatism response criteria. Rheumatoid factor (RF) and anticitrullinated protein/peptide antibodies (ACPAs) were detected. The 869C/T TGF-β and -174G/C IL-6 SNPs were analyzed by PCR amplification. US was performed to assess the bone surfaces of metacarpophalengeal (MCP), proximal interphalangeal (PIP) and metatarsophalangeal (MTP) joints by obtaining multiplanar scans. According to the number of erosions per joint, a semiquantitative score ranging from 0 to 3 was calculated in each anatomical site to obtain a MCP total erosion score (TES), a PIP TES and a MTP TES, all ranging from 0 to 30, and a global patient TES calculated as the sum of these scores (range, 0 to 90).
  
  
  RESULTS
  Patients carrying the TGF-β 869TT genotype showed a statistically significant lower MTP TES than those with the CC or CT genotype (mean MTP TES ± standard deviation for 869TT 6.3 ± 5.7 vs. 869CC/CT 11.7 ± 7.8; P = 0.011). Interestingly, patients with the TT genotype showed dichotomous behavior that was dependent on autoantibody status. In the presence of ACPAs and/or RF, the TT genotype was associated with lower erosion scores at all anatomical sites compared with the CC and CT genotypes. Conversely, the same 869TT patients showed higher erosion scores in the absence of ACPAs or RF.
  
  
  CONCLUSIONS
  In RA patients, TGF-β 869C/T SNPs could influence the bone-erosive damage as evaluated by US. The serological autoantibody status (ACPAs and RF) can modulate this interaction.
authors: Reumatologia, Dipartimento di Medicina Interna e Specialità Mediche, Sapienza Università di Roma, viale del Policlinico 155, I-00161 Rome, Italy. fulviaceccarelli@gmail.com
authors: Fulvia
authors: F
authors: Ceccarelli
authors: Carlo
authors: C
authors: Perricone
authors: Martina
authors: M
authors: Fabris
authors: Cristiano
authors: C
authors: Alessandri
authors: Annamaria
authors: A
authors: Iagnocco
authors: Cinzia
authors: C
authors: Fabro
authors: Elena
authors: E
authors: Pontarini
authors: Salvatore
authors: S
authors: De Vita
authors: Guido
authors: G
authors: Valesini
mesh_terms: D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging* / Q000235:genetics*; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D008662:Metacarpophalangeal Joint / Q000000981:diagnostic imaging; D008683:Metatarsophalangeal Joint / Q000000981:diagnostic imaging; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000235:genetics*; D014463:Ultrasonography
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; D016212:Transforming Growth Factor beta