title: [Fibronectin gene polymorphisms and clinical manifestations of mixed cryoglobulinemic syndrome: increased risk of lymphoma associated to MspI DD and HaeIII AA genotypes].
abstract: OBJECTIVE
  To analyse FN gene polymorphisms in type II mixed cryoglobulinemic syndrome (MCsn), an immune-complex mediated systemic vasculitis linked to hepatitis C virus (HCV) infection and characterized by rheumatoid factor (RF) positive B-cell proliferation at high risk for the progression into non Hogkin's lymphoma (NHL).
  
  
  METHODS
  Samples from eighty-one patients, with MCsn (type II serum cryoglobulins and clinical signs of vasculitis were studied. Sixty-five (65/81, 80.3%) patients were HCV-positive. Twenty-one (25.9%) patients had developed a B-cell NHL during the course of MCsn. Seventy-two patients with HCV-negative and MC-unrelated NHL and 110 healthy blood donors (HBDs) were taken as controls. HaeIIIb and MspI FN gene polymorphisms were analysed by ELISA, whenever possible.
  
  
  RESULTS
  HaeIIIb and MspI allele and genotypic frequencies did not differ between MCsn patients and HBDs. Of note, the DD-MspI allele and genotype frequencies did not differ between MCsn patients and HBDs. Of note, the DD-MspI (OR = 5.56; DI = 1.67-18.51, p = 0.0046) and the AA-HaeIIIb (OR = 5.54, CI = 1.64- 18.76, p = 0.0066) homozygosis appeared significantly and independently associated with the development of B-cell NHL in MCsn patients, with the HaeIIIbA allele possibly conferring an increased risk of NHL in the general population (OR = 1.72, CI = 1.128-2.635, p = 0.0133). In contrast, the major vasculitic manifestations, such as peripheral neuropathy, skin ulcers and glomerulonephritis tended to be associated with the counterpart MspI C allele. No association between FN plasma levels and FN genotypes was found.
  
  
  CONCLUSIONS
  Genotyping for MspI and HaeIIIb FN gene polymorphisms may be clinically relevant to define the predisposition to the major clinical manifestations in MCsn.
authors.affiliation: Cattedra di Reumatologia, Universita di Udine, Udine, Italia. martina.fabris@uniud.it
authors.forename: M
authors.initials: M
authors.lastname: Fabris
authors.forename: L
authors.initials: L
authors.lastname: Quartuccio
authors.forename: V
authors.initials: V
authors.lastname: De Re
authors.forename: G
authors.initials: G
authors.lastname: Pozzato
authors.forename: C
authors.initials: C
authors.lastname: Mazzaro
authors.forename: A
authors.initials: A
authors.lastname: Tavoni
authors.forename: C
authors.initials: C
authors.lastname: Ferri
authors.forename: S
authors.initials: S
authors.lastname: Salvin
authors.forename: A
authors.initials: A
authors.lastname: Lerussi
authors.forename: C
authors.initials: C
authors.lastname: Fabro
authors.forename: S
authors.initials: S
authors.lastname: Bombardieri
authors.forename: S
authors.initials: S
authors.lastname: De Vita
mesh_terms: D003449:Cryoglobulinemia / Q000150:complications / Q000175:diagnosis* / Q000235:genetics*; D015257:DNA-Cytosine Methylases / Q000235:genetics*; D005260:Female; D005353:Fibronectins / Q000235:genetics*; D005838:Genotype; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D008223:Lymphoma / Q000150:complications / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors
chemical_list: D005353:Fibronectins; D006023:Glycoproteins; C021240:tissue-factor-pathway inhibitor 2; D015257:DNA-Cytosine Methylases; C027823:Cytosine 5-methyltransferase