title: Analysis of association of LRP5, LRP6, SOST, DKK1, and CTNNB1 genes with bone mineral density in a Slovenian population.
abstract: The Wnt pathway has a bifunctional role in bone mass regulation, influencing osteoblasts and osteoclasts. The Wnt pathway genes are therefore candidate genes for susceptibility to osteoporosis. In our study, we focused on the effects of polymorphisms in selected Wnt pathway genes: low-density lipoprotein receptor-related proteins 5 and 6 (LRP5 and LRP6), Dickkopf1 (DKK1), sclerostin (SOST), and beta-catenin (CTNNB1). We genotyped 652 subjects for the following polymorphisms: A1330V in LRP5; I1062V in LRP6; E232K in DKK1; D32Y, G34V, and N287S in CTNNB1; and -1397_-1396insGGA in SOST. Bone mineral density (BMD) was also measured. The allele frequencies were as follows: for A1330V C:T = 87%:13%, for I1062V C:T = 20%:80%, and for -1397_-1396insGGA-:GGA = 64%:36%. The studied nucleotide changes in the DKK1 and CTNNB1 genes were shown not to be polymorphic. In a Slovenian population, no association was shown between lumbar spine and femoral neck BMD in A1330V (P = 0.151 and 0.243) and in I1062V (P = 0.209 and 0.405). We observed a difference between SOST genotypes, corresponding to an allele dose effect, which was borderline significant for lumbar spine and femoral neck BMD (P = 0.047 and 0.085); but this did not survive the adjustment for multiple testing. These results indicate that a larger sample size would be necessary to detect these subtle effects. Our results suggest that A1330V in LRP5, I1062V in LRP6, and -1397_-1396insGGA in SOST are not associated with BMD in the Slovenian population.
authors.affiliation: Faculty of Pharmacy, Department of Clinical Biochemistry, University of Ljubljana, Askerceva cesta 7, 1000, Ljubljana, Slovenia.
authors.forename: Simona
authors.initials: S
authors.lastname: Mencej-Bedrac
authors.forename: Janez
authors.initials: J
authors.lastname: Prezelj
authors.forename: Tomaz
authors.initials: T
authors.lastname: Kocjan
authors.forename: Radko
authors.initials: R
authors.lastname: Komadina
authors.forename: Janja
authors.initials: J
authors.lastname: Marc
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D015519:Bone Density / Q000235:genetics*; D019485:Bone Morphogenetic Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D026502:LDL-Receptor Related Proteins / Q000235:genetics* / Q000378:metabolism; D060492:Low Density Lipoprotein Receptor-Related Protein-5; D060488:Low Density Lipoprotein Receptor-Related Protein-6; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016103:Spinal Fractures / Q000235:genetics; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins; C495270:CTNNB1 protein, human; C501126:DKK1 protein, human; D005819:Genetic Markers; D036341:Intercellular Signaling Peptides and Proteins; D026502:LDL-Receptor Related Proteins; C555482:LRP5 protein, human; C555475:LRP6 protein, human; D060492:Low Density Lipoprotein Receptor-Related Protein-5; D060488:Low Density Lipoprotein Receptor-Related Protein-6; C422903:SOST protein, human; D051176:beta Catenin