Collagen type I alpha I and vitamin D receptor gene polymorphisms and bonemass in primary biliary cirrhosis

The potential influence of two gene polymorphisms, vitamin D receptor gene (VDR) and the gene encoding collagen type I alpha1 (COLIA1) Spl polymorphis ms, in the reduced bone mass observed in patients with primary biliary cirr hosis (PBC) was assessed in 61 women with PBC (age, 54.1 +/- 1.1 years) by restriction enzyme digestion of polymerase chain reaction (PCR)-amplified D NA extracted from whole blood. Bone mineral density (BMD) of the lumbar spi ne (L2-L4) and proximal femur were measured by X-ray absorptiometry. The se verity of liver disease and cholestasis was also evaluated, and changes in BMD were calculated after a mean period of 2.9 +/- 0.3 years in 41 patients . Sixteen patients (26%) had the BE, 20 the bb (33%), and 25 Bb (41%) VDR g enotypes, There were no significant baseline BMD differences among the 3 VD R genotypes. Forty-one patients (68%) had the SS, 16 the Ss (27%), and 3 th e ss (5%) COLIA1 genotypes. The baseline lumbar BMD was significantly lower in patients having the s allele than in the homozygote SS patients (Z-scor e, -0.76 +/- 0.24 vs. -0.10 +/-. 0.17, P = .02), The severity of cholestasi s was not related to the VDR or COLIA1 1 polymorphisms. Lumbar bone loss wa s independent of VDR and COLIA1 genotypes, but it was associated with chole stasis. In conclusion, the COLIA1 but not VDR polymorphism is a genetic mar ker of peak bone mass in patients with PBC, although the severity of choles tasis is the main factor for osteoporosis since it is associated with the r ate of bone loss.