[Decreased bone mineral density and gene polymorphism in primary biliary cirrhosis].
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.
Lakatos
Péter László
PL
Semmelweis Egyetem, Altalános Orvostudományi Kar, I. sz. Belgyógyászati Klinika, Budapest. kislakpet@bel1.sote.hu
Bajnok
Eva
E
Tornai
István
I
Folhoffer
Anikó
A
Horváth
Andrea
A
Lakatos
Péter
P
Szalay
Ferenc
F
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
C000716127:COL1A1 protein, human; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D007334:Insulin-Like Growth Factor I