Association of the A1330V and V667M polymorphisms of LRP5 with bone mineral density in Greek peri- and postmenopausal women.

Wnt signaling through low-density lipoprotein receptor-related protein 5 (LRP5) is an important determinant of bone mass regulation. To explore the influence of two LRP5 single nucleotide polymorphisms (SNPs) A1330V and V667M on bone mineral density (BMD) and serum levels of osteoprotegerin (OPG), receptor activator of nuclear factor-κB ligand (RANKL) and bone metabolic markers in a Greek female population. Two hundred and nine postmenopausal and twelve perimenopausal women aged 40-63 years were enrolled. All participants underwent spinal BMD evaluation. Genotyping of A1330V and V667M polymorphisms was performed by real-time polymerase chain reaction. Levels of OPG, soluble RANKL (sRANKL) and bone metabolic markers were measured. As regards A1330V SNP, women carrying CT/TT genotypes had lower spinal BMD than women with CC (p<0.0001). Regarding V667M SNP, spinal BMD was lower in women with GA/AA than in women with GG genotypes (p<0.0001). These differences remained significant after adjustment for age, years since menopause and body mass index. The A1330V and V667M polymorphisms were in strong linkage disequilibrium. A significant interaction between A1330V and V667M SNPs on spinal BMD was revealed. The haplotype with both risk alleles of the two SNPs (AT) conferred more risk for low BMD than the haplotypes with one risk allele (GT or AC) or the haplotype-reference (GC) (p=0.046, p=0.045, and p=0.010, respectively). No effect was observed on circulating OPG, sRANKL levels and bone metabolic markers. These findings demonstrate that the A1330V and V667M polymorphisms are associated with low BMD in peri- and postmenopausal Greek women.

Markatseli AE ，Hatzi E ，Bouba I ，Georgiou I ，Challa A ，Tigas S ，Tsatsoulis A ... -  《-》

Association between osteoprotegerin (OPG), receptor activator of nuclear factor-kappaB (RANK), and RANK ligand (RANKL) gene polymorphisms and circulating OPG, soluble RANKL levels, and bone mineral density in Korean postmenopausal women.

Kim JG ，Kim JH ，Kim JY ，Ku SY ，Jee BC ，Suh CS ，Kim SH ，Choi YM ... -  《MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY》

Polymorphism of LRP5, but not of TNFRSF11B, is associated with a decrease in bone mineral density in postmenopausal Maya-Mestizo women.

Osteoporosis is a complex disease characterized principally by low bone mineral density (BMD), which is determined by an interaction of genetic, metabolic, and environmental factors. The aim of this study was to analyze the possible association among one polymorphism of LRP5 and three polymorphisms of TNFRSF11B as well as their haplotypes with BMD variations in Maya-Mestizo postmenopausal women. We studied 583 postmenopausal women of Maya-Mestizo ethnic origin. A structured questionnaire for risk factors was applied and BMD was measured in lumbar spine (LS), total hip (TH), and femoral neck (FN) by dual-energy X-ray absorptiometry. DNA was obtained from blood leukocytes. One single-nucleotide polymorphism of LRP5 (rs3736228, p.A1330V) and three of TNFRSF11B (rs4355801, rs2073618, and rs6993813) were studied using real-time PCR allelic discrimination for genotyping. Differences between the means of the BMDs according to the genotype were analyzed with covariance. Deviations from Hardy-Weinberg equilibrium were tested. Pairwise linkage disequilibrium between single nucleotide polymorphisms was calculated by direct correlation r(2), and haplotype analysis of TNFRSF11B was conducted. The Val genotype of the rs3736228 (p.A1330V) of LRP5 was significantly associated with BMD variations at the LS, TH, and FN. None of the three polymorphisms of TNFRSF11B was associated with BMD variations. Our results show that p.A1330V was significantly associated with BMD variations at all three skeletal sites analyzed; the Val allele and the Val/Val genotype were those most frequently found in our population.

Canto-Cetina T ，Polanco Reyes L ，González Herrera L ，Rojano-Mejía D ，Coral-Vázquez RM ，Coronel A ，Canto P ... -  《-》

Association of a single-nucleotide variation (A1330V) in the low-density lipoprotein receptor-related protein 5 gene (LRP5) with bone mineral density in adult Japanese women.

Ezura Y ，Nakajima T ，Urano T ，Sudo Y ，Kajita M ，Yoshida H ，Suzuki T ，Hosoi T ，Inoue S ，Shiraki M ，Emi M ... -  《-》

Association between Wnt signaling pathway gene polymorphisms and bone response to hormone therapy in postmenopausal Korean women.

Kim H ，Choe SA ，Ku SY ，Kim SH ，Kim JG ... -  《-》