Our study showed a strong association between bone mineral density and polymorphisms in the FDPS gene, and a borderline association with LRP5 and SOST polymorphisms in postmenopausal Romanian women with osteoporosis.No association was found for VKORC1.
Evidence suggested a role for genetic variation in IL6 and LRP5 in conferring risk for osteoporosis in Caucasian women, with the latter manifest only in smokers.
Her half-brother, treated with cabergoline for a microprolactinoma, also had osteoporosis of the lumbar spine on dual-energy x-ray absorptiometry and carried the same LRP5 mutation.
Mutational analysis uncovers monogenic bone disorders in women with pregnancy-associated osteoporosis: three novel mutations in LRP5, COL1A1, and COL1A2.
The aim of the study was to evaluate the frequency of genotypes and alleles of single nucleotide polymorphism (SNP) rs4988321 and rs312009 of LRP5 in Polish postmenopausal women with osteopenia (n = 109) and osteoporosis (n = 333).
In comparison to age-matched controls we detected profound changes in the transcriptome in hMSC-OP, e.g. enhanced mRNA expression of known osteoporosis-associated genes (LRP5, RUNX2, COL1A1) and of genes involved in osteoclastogenesis (CSF1, PTH1R), but most notably of genes coding for inhibitors of WNT and BMP signaling, such as Sclerostin and MAB21L2.
The introduction of another variable, the ER genotype, in the analysis of VDR genetic determination of BMD, may represent a useful model in the identification of patients at risk of developing a multigenic disorder like osteoporosis.
The risk of osteoporosis in the VDR-rs2228570 polymorphism T-allele carriers was significantly higher than that in CC (CT/TT versus CC) individuals (adjusted odds ratio [OR] [95% confidence interval (CI)] = 1.76 [1.33-2.22]).
Association analyses and multivariate two-step regression model of social and molecular parameters, demonstrated that in comparison to the VDR, ESR, CTR polymorphisms, physical activities and healthy diet, associated with outdoor work are the best favourable prognostic factors for osteoporosis.
Thus, the greater therapeutic effects of AH-1 than those of 1α,25(OH)<sub>2</sub>D<sub>3</sub> in in vivo studies using osteoporosis rat models may be due to 24R-hydroxy-AH-1 whose VDR affinity was 91% of that of AH-1.
In conclusion, these data, along with the absence of relationships between VDR gene polymorphisms and peak bone mass that we recently reported, suggest that the determination of VDR genotypes is probably not a useful clinical test for the risk assessment of osteoporosis.
Recent developments in the molecular epidemiology of osteoporosis have shown the interest, but also the limitations, of specific molecular markers, such as the vitamin D receptor gene polymorphisms Bsm 1 and Fok 1, to explain bone mineral density differences across the population.
A series of common polymorphisms in the vitamin D receptor gene were recently reported to be associated with bone density and risk of osteoporosis (Morrison et al., Nature (Lond.), 367: 284-287, 1994).
These results suggest that restriction fragment length polymorphism analysis of the VDR gene with a Bsm1 restriction enzyme in Koreans is not helpful for early detection of patients at risk of developing osteoporosis.
The microarray data from the Gene Expression Omnibus database accession number GSE51686, were downloaded and used to identify differentially expressed genes (DEGs) in fracture callus tissue samples obtained from the femora of type I collagen (Col1a1)‑kringle containing transmembrane protein 2 (Krm2) mice and low density lipoprotein receptor‑related protein 5‑/‑ (Lrp5‑/‑) transgenic mice of osteoporosis compared with those in wild‑type (WT) mice.