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-1227C>T polymorphism in the pleiotrophin gene promoter influences bone mineral density in postmenopausal women
Mencej Bedrač, Simona ...
Our gene expression microarray data of primary cultures of osteoblasts revealed that the expression of the pleiotrophin (PTN) gene is decreased in osteoporosis. PTN is involved in osteoblasts' ...proliferation and differentiation, response to mechanical stimuli and cross-talk with Wnt signaling. On the basis of these findings, we studied the PTN gene as a candidate gene for genetic susceptibility to osteoporosis. The aim of the study was to evaluate the association of two PTN gene promoter polymorphisms with osteoporotic phenotype in postmenopausal women. 530 postmenopausal women,480 without and 50 with hip fracture, were genotyped for the presence ofPTN gene promoter polymorphisms -1734C>T (rs161335) and -1227C>T (rs321198).Three common haplotypes, CC (14.2%), CT (42.8%) and TC (42.9%), were inferred. Bone mineral densities (BMDs) at lumbar spine and (contralateral) hip were measured. In non-osteoporotic postmenopausal women without hip fracture, the association of -1227C>T and CT haplotype with lumbarspine BMD was shown (p=0.014 and 0.014). No other significant association of the studied genotypes and haplotypes in the PTN gene promoter with BMDs was found. Comparing age-matched postmenopausal women with and without hip fractures, no differences in frequency distributions of the studied genotypes and haplotypes was shown. For the first time we have shown that, in postmenopausal women, the PTN gene promoter polymorphism -1227C>T and CT haplotype could contribute to the genetic background of osteoporosis, but these findings need further functional and clinical confirmation.
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