Relationship between polymorphisms and mutations at rs7125942 and rs3736228 of LRP5 gene and bone metabolism in postmenopausal women.

To analyze the relationship between the polymorphism and mutation of rs7125942 and rs3736228 locus in the low-density lipoprotein receptor-related protein 5 (LRP5) genotype and bone mineral density (BMD) in postmenopausal women in Xinjiang, China, to provide a basis for prevention and treatment of the disease. According to the results of dual-energy X-ray (DEXA) determination of BMD, the 136 subjects were divided into three groups: Group A: normal bone mass, Group B: osteopenia, Group C: osteoporosis. 1. Age, body, mass index (BMI), and menopause of all subjects were recorded. 2. Fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), and clinical biochemical data were determined. 3. LRP5 locus polymorphisms were determined by time-of-flight mass spectrometry. 1. Compared with group A, the age, ALP, Cr, and BUN levels in group B and group C were increased, but UA levels were lower (P < 0.05), and Serum P was higher in the group C (P < 0.05). 2. There was no statistically significant difference in the prevalence of diabetes between the three groups (P > 0.05). 3. The ROC curves for different BMD sites such as L1, L2, L3, L4, L total, and femoral neck were 0.929, 0.955, 0.901, 0.914, 0.885, and 0.873 (P < 0.01). 4. At rs7125942 locus, there was statistically significant difference in the distribution of wild-type (CC) and mutant (CG) with the normal bone mass (NBM) group and the abnormal bone mass (ABM) group (P < 0.05). 5. At rs7125942 locus, compared with wild-type (CC), mutant (CG) had lower LDL and FPG in NBM group (P < 0.05), and lower serum ALP in the ABM group (P < 0.05). At rs3736228 locus, the BMD (Femoral neck) of mutant (CT/TT) was lower than that of wild-type (CC) in the NBM group (P < 0.05). 6. Age and menopausal years were negatively correlated with BMD of the femoral neck and L1-4 (P < 0.05), and BMI and TG were positively (P < 0.05), and the results of multiple linear regression analysis showed that age, BMI, and TG were both independent factors affecting BMD (P < 0.05).

Li J ，Li Y ，Li S ，Lu Y ，Rai P ... -  《Journal of Orthopaedic Surgery and Research》

A Study of the Relationship between the Polymorphism and Mutation of rs682429 and rs3781590 in the LRP5 Gene and Bone Metabolism in Postmenopausal Type 2 Diabetic Women in Xinjiang.

To explore the expression of the polymorphism and mutation of rs682429 and rs3781590 in the low-density lipoprotein receptor-related protein 5 (LRP5) genotype and to analyse the relationship of bone mineral density (BMD) and bone metabolism markers in postmenopausal women with type-2 diabetes mellitus (T2DM) in Xinjiang, China, to provide a basis for prevention and treatment of the disease. A total of 136 postmenopausal women were included in the study. According to the results of an oral glucose tolerance test (OGTT) and dual-energy X-ray (DEXA) determination of BMD, the study subjects were divided into 4 groups: group A: normal OGTT+normal bone mass group; group B: normal OGTT+osteoporotic (OP) group; group C: T2DM+normal bone mass group; group D: T2DM+osteoporotic (OP) group. Calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), and clinical biochemical data were determined; haemoglobin A1c (HbA1c) was measured by HPLC; BMD of the femoral neck, hip, and lumbar spine (L1-4) was measured by dual-energy X-ray (DEXA); and the rs682429 and rs3781590 polymorphisms of the LRP5 gene were detected by time-of-flight mass spectrometry (TOF MS). (1) The rs682429 polymorphism of the LRP5 genotype distribution was statistically significant (P < 0.05) in group B compared with group A. (2) The triglycerides (TG) of women with the CT/TT genotype (mutant type) were higher than those of women with the CC genotype (wild type) (2.37 ± 1.30 vs. 1.52 ± 0.83, P < 0.05) at the rs3781590 site of the LRP5 gene in group D. (3) Multiple linear regression analysis showed that TG (β = 0.034, P < 0.05) and body mass index (BMI) (β = 0.013, P < 0.05) were the influencing factors of BMD (L1-4) in T2DM patients. TG (β = 0.022, P < 0.05), BMI (β = 0.009, P < 0.05), and duration of menopause (β = 0.005, P < 0.05) were the influencing factors of BMD (hip). (1) The rs682429 polymorphism site in the LRP5 gene may be involved in bone metabolism in postmenopausal women from Xinjiang. (2) The rs3781590 mutation in the LRP5 gene from these subjects may be involved in lipid metabolism. (3) Among postmenopausal women with type 2 diabetes mellitus and bone mass abnormality in the Xinjiang Shihezi area, high BMI and TG are protective factors against increased BMD. Duration of menopause is a risk factor for increased BMD.

Li J ，Li S ，Zhao H ，Li J ，Wang S ，Shi Y ... -  《-》

The relationship between LRP5 rs556442 and rs638051 polymorphisms and mutations and their influence on bone metabolism in postmenopausal Xinjiang women with type 2 diabetes.

Li J ，Song M ，Li S ，Wang X ，Zhao H ，Hou Z ... -  《Advances in Clinical and Experimental Medicine》

Impact of genetic variants of IL-6, IL6R, LRP5, ESR1 and SP7 genes on bone mineral density in postmenopausal Mexican-Mestizo women with obesity.

Since obesity and osteoporosis present a high genetic predisposition and polymorphisms of IL-6, IL6R, LRP5, ESR1 and SP7 may influence the risk of both diseases, the aim of this study was to analyze the possible association of polymorphisms in these genes, as well as their haplotypes, with BMD variations in postmenopausal Mexican-Mestizo women with grade 2 or grade 3 obesity. One hundred eighty unrelated postmenopausal women with grade 2 or grade 3 obesity were included. BMD was measured in total hip and lumbar spine by dual-energy X-ray absorptiometry. DNA was obtained from blood leukocytes. Rs1800795 of IL-6, rs2228145 of IL6R, rs3736228 of LRP5, rs9340799 (XbaI) and rs2234693 (PvuII), of ESR1, rs10876432 and rs2016266, of SP7 (and their haplotypes), were studied by real-time PCR allelic discrimination. Deviations from Hardy-Weinberg equilibrium were tested. Pairwise linkage disequilibrium between single nucleotide polymorphisms was calculated by direct correlation r(2), and haplotype analysis was conducted. Using WHO criteria, 54.5% had grade 2 obesity, and 45.5% had grade 3 obesity. Regarding DXA results, 11.1% women had osteoporosis, 41.7% had osteopenia, and 47.2% had normal BMD. Genotype and haplotype analysis showed no significant differences with BMD variations at the lumbar spine, total hip or femoral neck. We did not find a significant association between the polymorphisms analyzed or their haplotypes and BMD variations in postmenopausal women with obesity. The higher BMD observed in women with obesity could be the result of an adaptive response to the higher loading of the skeleton.

Méndez JP ，Rojano-Mejía D ，Coral-Vázquez RM ，Coronel A ，Pedraza J ，Casas MJ ，Soriano R ，García-García E ，Vilchis F ，Canto P ... -  《-》

Low density lipoprotein receptor-related protein 5 gene polymorphisms and osteoporosis in Thai menopausal women.

Kitjaroentham A ，Hananantachai H ，Phonrat B ，Preutthipan S ，Tungtrongchitr R ... -  《-》