title: [Decreased bone mineral density and gene polymorphism in primary biliary cirrhosis].
abstract: Genetic factors have been implicated in the pathogenesis of osteoporosis, which is a common disorder in primary biliary cirrhosis (PBC). Insulin-like growth factor I (IGF-I) gene microsatellite repeat polymorphism was found to be associated with osteoporosis in some studies and collagen type I alpha 1 (COLIA1) SP1 "s" allele was associated with lower bone mineral density (BMD) in PBC. IGF-I treatment restored osteopenia and reduced fibrogenesis in experimental cirrhosis. We investigated IGF-I and COLIA1 gene polymorphisms and BMD in Hungarian PBC patients.
  
  
  METHODS
  70 female patients with PBC were enrolled (mean age: 57.6 yrs, range: 37-76 yrs, each AMA M2 positive, stage II-IV). 139 age-matched female subjects served as controls (mean age: 55.9 yrs, range: 43-72 yrs). COLIA1 and IGF-I microsatellite repeat polymorphisms were determined by PCR. Bone mineral density (BMD) was measured by dual energy x-ray absorptiometry (Lunar, Prodigy, WI, USA) in lumbar spine (LS) and femoral neck (FN).
  
  
  RESULTS
  The IGF-I polymorphism was not different between PBC patients (192/192 = 34.2%, 194/192 = 28.6%, other = 37.2%) and controls (192/192 = 38.2%, 194/192 = 30.9%, other = 30.9%). The genotype frequency of COLIA1 polymorphism was also not different between PBC patients (SS = 72.9%, Ss = 22.8% and ss = 4.3%) and controls (SS = 58.4%, Ss = 35.9% and ss = 5.7%), however the "s" allele was significantly less frequent in patients with PBC (p = 0.038). Osteoporosis was present in 22 patients (31.4%). The IGF-I 192/192 allele was associated with higher FN Z-score compared to other genotypes (p = 0.036).
  
  
  CONCLUSIONS
  In contrast to previous studies the "s" allele was less frequent in patients with PBC, and its presence was not associated with lower bone mineral density. Since IGF-I polymorphism was associated to BMD, it may be hypothesized that IGF-I microsatellite repeat polymorphism together with other genetic and environmental factors may be involved in the complex regulation of BMD in PBC.
authors.affiliation: Semmelweis Egyetem, Altalános Orvostudományi Kar, I. sz. Belgyógyászati Klinika, Budapest. kislakpet@bel1.sote.hu
authors.forename: Péter László
authors.initials: PL
authors.lastname: Lakatos
authors.forename: Eva
authors.initials: E
authors.lastname: Bajnok
authors.forename: István
authors.initials: I
authors.lastname: Tornai
authors.forename: Anikó
authors.initials: A
authors.lastname: Folhoffer
authors.forename: Andrea
authors.initials: A
authors.lastname: Horváth
authors.forename: Péter
authors.initials: P
authors.lastname: Lakatos
authors.forename: Ferenc
authors.initials: F
authors.lastname: Szalay
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D015519:Bone Density; D001847:Bone Diseases / Q000209:etiology* / Q000378:metabolism; D016022:Case-Control Studies; D024042:Collagen Type I / Q000235:genetics*; D000090602:Collagen Type I, alpha 1 Chain; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D008105:Liver Cirrhosis, Biliary / Q000150:complications* / Q000235:genetics / Q000378:metabolism*; D018895:Microsatellite Repeats; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic
chemical_list: C000716127:COL1A1 protein, human; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D007334:Insulin-Like Growth Factor I