title: -238 and +489 TNF-alpha along with TNF-RII gene polymorphisms associate with the diffuse phenotype in patients with Systemic Sclerosis.
abstract: OBJECTIVE
  To investigate possible associations of TNF-alpha and TNF-RII gene polymorphisms with diffuse or limited skin involvement phenotype in a cohort of Systemic Sclerosis (SSc) patients.
  
  
  METHODS
  One-hundred and fourteen consecutive SSc patients attending the referral centres of three academic hospitals in Italy (University of Naples, Pavia and Udine), 56 with the diffuse (dcSSc) and 58 with limited (lcSSc) skin involvement subsets, and 170 healthy blood donors (HBDs) were included in the study. The extracted DNA was genotyped for the following polymorphisms: TNF-alpha (-238, +489) and TNF-RII (+196), using the polymerase chain reaction (PCR) and the restriction enzymes BamHI, HpyCH4 IV and NlaIII, respectively.
  
  
  RESULTS
  The AG/AA (presence of allele A) genotypes in position -238 and the AG genotype in position +489 of the TNF-alpha gene were found significantly increased in SSc, as a whole, when compared with healthy blood donors (chi(nu=2)(2)=4.48, p=0.03 for -238 and chi(nu=2)(2)=7.82, p=0.02 for +489, respectively). The rare GG genotype in exon 6 (codon 196) of the TNF-RII gene was also found increased in SSc compared to HBDs, even though the difference did not show statistical significance (chi(nu=2)(2)=3.56, p=0.17). The strength of the association was mainly due to the dcSSc phenotype (Fisher test, p=0.04 for -238, chi(nu=2)(2)=10.07, p<0.01 for +489 and chi(nu=2)(2)=6.25, p=0.04 for the +196 TNF-RII, respectively).
  
  
  CONCLUSIONS
  TNF-alpha and TNF-RII gene polymorphisms seem to contribute to the development of SSc and in particular to the diffuse phenotype.
authors.affiliation: Division of Rheumatology, UCSC-Catholic University of Rome, Rome, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Tolusso
authors.forename: Martina
authors.initials: M
authors.lastname: Fabris
authors.forename: Roberto
authors.initials: R
authors.lastname: Caporali
authors.forename: Giovanna
authors.initials: G
authors.lastname: Cuomo
authors.forename: Miriam
authors.initials: M
authors.lastname: Isola
authors.forename: Franca
authors.initials: F
authors.lastname: Soldano
authors.forename: Carlomaurizio
authors.initials: C
authors.lastname: Montecucco
authors.forename: Gabriele
authors.initials: G
authors.lastname: Valentini
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Ferraccioli
mesh_terms: D001323:Autoantibodies / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D005810:Multigene Family; D010641:Phenotype; D011110:Polymorphism, Genetic; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000235:genetics* / Q000378:metabolism; D012189:Retrospective Studies; D012595:Scleroderma, Systemic / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism
chemical_list: D001323:Autoantibodies; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha