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
... -
《-》
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》
Relationship Between Sclerostin (SOST) Expression and Genetic Loci rs851056, rs1230399 Polymorphisms and Bone Mineral Density in Postmenopausal Women with Type 2 Diabetes in Xinjiang.
The Wnt signaling pathway plays a valuable role in bone metabolism. SOST is a major inhibitor of the Wnt signaling pathway. The expression of SOST and genetic polymorphism might be associated with bone mineral density in postmenopausal women with type 2 diabetes mellitus (T2DM).
This study aims to explore whether SOST protein expression and genetic locus rs851056, rs1230399 polymorphism is associated with bone mineral density in postmenopausal women with T2DM in Xinjiang.
A total of 136 Xinjiang postmenopausal women were divided into four groups: A (-/-), B (±), C (-/+), and D (+/+) by assessing their OGTT and bone mass. Genetic polymorphisms were determined using the mass ARRAY mass spectrometer.
1) Genotypes and allele frequencies at rs851056 were statistically significant differences in groups B and D patients compared to group A, respectively. 2) Individuals carrying the GG genotype had lower HDL, Ca, and ALP as compared to those carrying the GC/CC genotypes in group C. In contrast, individuals carrying the GG genotype had higher BMD (L1-4) as compared to those carrying the GC/CC genotypes in group D. 3) SOST protein expression levels were higher in groups C and D than in group A. 4). BMD (L1-4) was negatively correlated with SOST protein. 5) Multiple linear regression analysis for BMD-dependent variables showed that the decrease of BMI and TG were risk factors for BMD (L1-4), besides, the decrease of BMI, ALP, and extended years of menopause were all risk factors for BMD (femoral neck).
SOST protein expression and genetic locus rs851056, rs1230399 polymorphism are associated with bone mineral density in postmenopausal women with type 2 diabetes mellitus in Xinjiang.
Li J
，Ren Y
，Li S
，Li J
... -
《Diabetes Metabolic Syndrome and Obesity-Targets and Therapy》
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