Dataset Information

Association of LRP5 gene polymorphism with type 2 diabetes mellitus and osteoporosis in postmenopausal women.

ABSTRACT: This study was to explore the association of low-density lipoprotein receptor related protein 5 (LRP5) gene polymorphism with bone mineral density (BMD), bone turnover markers and glycometabolism in postmenopausal women with type 2 diabetes mellitus (T2DM) and/or osteoporosis (OP) in Shanghai. 354 unrelated Han Chinese post-menopausal women were recruited from Shanghai and divided into 4 groups: OP group (n=90), T2DM group (n=96), T2DM + OP group (n=90) and control group (n=78). The LRP5 genotypes were determined by DNA sequencing. The BMD was measured by dual-energy X-ray absorptiometry. The bone transformation indicators and glycometabolism index (HbA1c and Fasting insulin) were also detected. The association of LRP5 polymorphism with BMD, bone turnover markers and glycometabolism was evaluated. Result showed that, In OP group, the BMD of L2-4 was higher in patients with rs3736228 CC genotype than those with CT/TT genotypes (P<0.05). After adjustment for age, body mass index (BMI) and years of menopause, A1330V polymorphism was still associated with BMD of L2-4 (P<0.01). In the control group, HbA1c was significantly higher in patients with A1330V CC genotype than those with CT/TT genotypes (P<0.05), but no significant difference was found after adjustment for BMI, age and years of menopause (P>0.05). Thus, LRP5 gene is an impressionable gene in postmenopausal women with OP in Shanghai. T2DM patients have a high BMD when compared with controls, which may be related to BMI and FINS. LRP5 genotype is not an impressionable gene in postmenopausal women with T2DM in Shanghai.

SUBMITTER: Xuan M

PROVIDER: S-EPMC3902264 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Association of LRP5 gene polymorphism with type 2 diabetes mellitus and osteoporosis in postmenopausal women.

Xuan Miao M Wang Yonglan Y Wang Wenxing W Yang Jun J Li Ying Y Zhang Xiuzhen X

International journal of clinical and experimental medicine 20140115 1

This study was to explore the association of low-density lipoprotein receptor related protein 5 (LRP5) gene polymorphism with bone mineral density (BMD), bone turnover markers and glycometabolism in postmenopausal women with type 2 diabetes mellitus (T2DM) and/or osteoporosis (OP) in Shanghai. 354 unrelated Han Chinese post-menopausal women were recruited from Shanghai and divided into 4 groups: OP group (n=90), T2DM group (n=96), T2DM + OP group (n=90) and control group (n=78). The LRP5 genotyp ...[more]

PMID: 24482712

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Project description:Osteoporosis is a polygenic disorder and has been demonstrated to be associated with ~30 candidate genes, the majority of which have also been implicated in the regulation of bone mineral density (BMD). Vitamin D receptor (VDR) is the candidate gene that has been most extensively studied. Certain studies have reported that the VDR single nucleotide polymorphism ApaI is associated with the risk of osteoporosis in Caucasian and African women. However, this association has not yet been studied in postmenopausal Han Chinese women in the Xinjiang area. In the present study, ApaI polymorphisms of VDR were defined by polymerase chain reaction-restriction fragment length polymorphism, in order to analyze the distribution of ApaI polymorphisms in postmenopausal Han Chinese women from Xinjiang. BMD was measured by dual energy X-ray absorptiometry at the lumbar spine (L2-4), Ward's triangle, great trochanter and femoral shaft. A total of 336 women were included in this study. The genotype distribution of ApaI was consistent with the Hardy-Weinberg equilibrium (all P>0.05). There were no significant differences in ApaI genotype frequencies between the 90 cases in the osteoporosis group and 246 cases in the non-osteoporosis group (P=0.946). Meanwhile, it was identified that BMD values of the tested locations were negatively correlated with age (P<0.05) and positively correlated with body mass index (BMI; P<0.05). On further attribution risk analysis, BMD was identified as a risk factor [odds ratio (OR): 0.464, 95% confidence interval (CI): 0.372-0.580, P=0.001] and BMI a protective factor (OR: 1.502, 95% CI: 1.008-2.240, P=0.032) in osteoporosis. When BMD was adjusted for confounding factors including age and BMI, it was observed that the ApaI polymorphism was not associated with BMD at the sites tested (P>0.05). In conclusion, the present study identified no significant association of the common VDR polymorphism ApaI with BMD at several skeletal sites in postmenopausal Han Chinese women in the Xinjiang area. Age was negatively correlated with BMD at different sites and identified as a risk factor; while BMI was positively correlated with BMD and identified as a protective factor.

Project description:This study aims to investigate the relationship between single nucleotide polymorphisms (SNPs) of sex hormone binding globulin (SHBG) and type 2 diabetes mellitus (T2DM) in an Uighur population. One hundred and fourteen T2DM male patients (with a history of diabetes or diagnosed as diabetic by the oral glucose tolerance test) and 173 healthy males from the Uighur ethnic group were included in the study to test the following SNPs of SHBG: rs727428, rs1799941, rs6259, rs6257, rs858521, rs858518, rs3760213, and rs11078701. The body mass index (BMI), blood pressure, and waist circumference, and lipid, glucose, HbA1c, insulin, HOMA-IR, testosterone, and SHBG levels of enrolled individuals were measured. We used the t-test or rank sum test and Chi-square test to analyze the difference and compare numeration data, respectively, between the case and control groups. Comparisons among multiple groups were carried out using analysis of variance, and the correlation between variables was determined by nonparametric Spearman rank correlation analysis; multivariate logistic regression analysis was used to assess the risk of abnormal glucose in the two groups. There was a significant difference (P < 0.05) in BMI, blood pressure, and waist circumference, and lipid, glucose, HbA1c, insulin, and HOMA-IR levels between the case and control groups. The risk factors for diabetes included testosterone (P = 0.042) and SHBG (P = 0.001). The distribution of rs858521 (P = 0.001), rs1799941 (2.3%, P = 0.032), rs6259 (2.5%, P = 0.040), and rs727428 (3.4%, P = 0.016) was significantly different between the case and control groups (P < 0.05). In the control group, there was linkage disequilibrium (LD) between rs727428 and rs6259, while in the case group LD was found among rs858518, rs3760213, rs1799941, and rs6257. The frequency of rs858518-rs3760213-rs1799941-rs6257 haplotype TCGC was significantly different between the two groups (P = 0.033). Both testosterone and SHBGwere found to be risk factors of diabetes in the Uighur population, and SNPs of SHBG may contribute to T2DM.

Project description:ObjectivesTo assess LRP5-/6 gene polymorphisms and its association with risk of abnormal bone mass (ABM) in postmenopausal women.MethodsThe study recruited 166 patients with ABM (case group) and 106 patients with normal bone mass (control group) based on bone mineral density (BMD) results. Multi-factor dimensionality reduction (MDR) was used to analyze the interaction between the Low-density lipoprotein receptor-related protein 5 (LRP5) gene (rs41494349, rs2306862) and the Low-density lipoprotein receptor-related protein 6 (LRP6) gene (rs10743980, rs2302685) and the subjects' clinical characteristics of age and menopausal years.Results(1) Logistic regression analysis showed that the subjects with the CT or TT genotype at rs2306862 had a higher risk of ABM than those with the CC genotype (OR = 2.353, 95%CI = 1.039-6.186; OR = 2.434, 95%CI = 1.071, 5.531; P < 0.05). The subjects with the TC genotype at rs2302685 had a higher risk of ABM than those with the TT genotype (OR = 2.951, 95%CI = 1.030-8.457, P < 0.05). (2) When taking the three Single-nucleotide polymorphisms (SNPs) together, the accuracy was the highest with the cross-validation consistency of 10/10 (OR = 1.504, 95%CI:1.092-2.073, P < 0.05), indicating that the LRP5 rs41494349 and LRP6 rs10743980, rs2302685 were interactively associated with the risk of ABM. (3) Linkage disequilibrium (LD) results revealed that the LRP5 (rs41494349,rs2306862) were in strong LD (D' > 0.9, r2 > 0.3). AC and AT haplotypes were significantly more frequently distributed in the ABM group than in the control group, indicating that subjects carrying the AC and AT haplotypes were associated with an increased risk of ABM (P < 0.01). (4) MDR showed that rs41494349 & rs2302685 & rs10743980 & age were the best model for ABM prediction. The risk of ABM in "high-risk combination" was 1.00 times that of "low-risk combination"(OR = 1.005, 95%CI: 1.002-1.008, P < 0.05). (5) MDR showed that there was no significant association between any of the SNPs and menopausal years and ABM susceptibility.ConclusionThese findings indicate that LRP5-rs2306862 and LRP6-rs2302685 polymorphisms and gene-gene and gene-age interactions may increase the risk of ABM in postmenopausal women. There was no significant association between any of the SNPs and menopausal years and ABM susceptibility.

Dataset Information

Association of LRP5 gene polymorphism with type 2 diabetes mellitus and osteoporosis in postmenopausal women.

Publications

Association of LRP5 gene polymorphism with type 2 diabetes mellitus and osteoporosis in postmenopausal women.

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