The polymorphism of Insulin-like growth factor-I (IGF-I) is related to osteoporosis and bone mineral density in postmenopausal population.
ABSTRACT: OBJECTIVE:It has been shown that Insulin-like growth factor-1 (IGF-1) may be related with bone mineral density (BMD) or osteoporosis. But there are few evidences on the role of genetic variation of IGF-1 on the BMD or osteoporosis. We observed the relationship between polymorphisms of IGF-1(rs35767, rs2288377 and rs5742612) with osteoporosis and BMD in the postmenopausal female population in our study. METHODS:A total of 216 postmenopausal women with a primary diagnosis of osteoporosis and 220 normal healthy women were included in the study. Genomic DNA of IGF-1 rs35767, rs2288377 and rs5742612 was extracted from the whole blood using QIAamp blood DNA mini kits (QIAGEN, Hilden, Germany) according to the methods recommended by the manufacturer. RESULTS:We found that T allele of rs35767 had higher increased risk of osteoporosis (OR=1.34, 95%CI=1.0-1.81). Those carrying T allele of rs35767 had a significant lower BMD at L1-L4 vertebrae, femoral neck, total hip and trochanter when compared with those carrying C allele (P < 0.05). In addition, the BMD of L1-L4 vertebrae, femoral neck, total hip and trochanter decreased by 2.09%, 3.74%, 3.52% and 2.54% in women carrying T alleles compared with those carrying C alleles. CONCLUSION:Our study suggests that polymorphism in IGF-I rs35767 was significantly associated with BMD and osteoporosis in postmenopausal female population, and polymorphism of rs35767 could be a marker for lower BMD and risk of osteoporosis.
Project description:We conducted a case-control study in a Chinese postmenopausal population, and explore the potential role of the promoter region variation of the IGF-1 gene in bone mineral density and osteoporosis risk. 485 postmenopausal women with a primary diagnosis of osteoporosis and 485 age-matched controls were selected between 2012 and 2014. The Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) was used for rs35767, rs2288377 and rs5742612 of IGF-1 genotyping. By conditional regression analysis, individuals carrying TT genotype and CT+TT genotype of rs35767 were found to be correlated with an elevated risk of osteoporosis, with adjusted ORs (95% CI) of 1.90 (1.23-2.93) and 1.35 (1.04-1.76), respectively. Our study found that CT+TT genotype of rs35767 was significantly associated with moderate increased risk of osteoporosis in smokers and drinkers, and the ORs (95% CI) were 2.11 (1.06-4.20) and 2.36 (1.29-4.32), respectively. We found that those carrying CT+TT genotype of rs35767 had a significant lower BMD levels at L1-L4 vertebrae, femoral neck, total hip and trochanter compared to those with CC genotype. Our study suggests that TT genotype and CT+TT genotype of IGF-I rs35767 were associated with risk of osteoporosis and BMD levels.
Project description:Osteoporosis is a systemic metabolic and serious skeletal disease commonly observed among the elderly. Insulin-like growth factors (IGFs) are critical regulators for bone cell function. We estimated the role of IGF-I rs35767, rs2288377 and rs5742612 polymorphisms in the susceptibility to osteoporosis in a population of China, and assessed gene-environment interactions. A total of 346 patients with osteoporosis and 346 controls were enrolled. Genotyping of IGF-I rs35767, rs2288377 and rs5742612 was amplified and performed with the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The TA and AA genotypes displayed elevated risk of developing osteoporosis (TA vs TT: OR=1.54, 95% CI=1.11-2.15; AA vs TT: OR=3.65, 95% CI=2.09-6.37). Compared with TT individuals, individuals with the TA+AA genotype had a substantial increased susceptibility to osteoporosis (OR=1.80, 95% CI=1.31-2.46). In recessive model, the AA genotype of rs2288377 displayed 2.89 folds risk of osteoporosis (adjusted OR=2.89, 95% CI=1.70-4.89). A significant negative interaction was found between IGF-I rs2288377 and BMD levels for femoral neck (r=-0.14, P<0.001), total hip (r=-0.09, P<0.001) and trochanter (r=-0.13, P<0.001). In conclusion, we suggest that IGF-I rs2288377 polymorphism had a strong influence on osteoporosis susceptibility in this Chinese population.
Project description:Insulin-like growth factor-1 (IGF-1) plays an important role in the regulation of bone formation and mineralization. We aimed to perform a meta-analysis to assess the association of three IGF-1 single nucleotide polymorphisms (SNPs) rs35767, rs2288377, and rs5742612 with osteoporosis risk.A systematic search of PubMed, Web of Science, Embase, Medline, Scopus, CNKI, and Wanfang databases was conducted. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using a fixed effects model.Four Chinese case-control studies with a total of 2807 participants were included in this meta-analysis. The results revealed an association between rs35767 and osteoporosis risk in all study subjects (women and men) in dominant (OR 1.32, 95% CI 1.13-1.53, P?<?.001), recessive (OR 1.73, 95% CI 1.35-2.21, P?<?.001), homozygote (OR 1.89, 95% CI 1.46-2.45, P?<?.001), and allelic (OR 1.31, 95% CI 1.18-1.47, P?<?.001) models. Subgroup analysis according to gender showed that rs35767 was associated with osteoporosis risk in women under dominant (OR 1.29, 95% CI 1.08-1.54, P?=?.005), recessive (OR 1.59, 95% CI 1.19-2.12, P?=?.002), homozygote (OR 1.73, 95% CI 1.28-2.34, P?<?.001), and allelic (OR 1.28, 95% CI 1.12-1.47, P?<?.001) models. Meta-analysis did not find associations of rs2288377 and rs5742612 with osteoporosis risk. There was no evidence of between-study heterogeneity and publication bias.Our results suggest that rs35767 is associated with osteoporosis risk in Chinese, whereas there is no association of rs2288377 and rs5742612 with osteoporosis risk.
Project description:BACKGROUND To investigate associations of the CA microsatellite and rs35767, rs5742612, and rs2288377 polymorphisms and the single nucleotide polymorphism (SNP) haplotypes with and without the CA microsatellite in the IGF1 promoter with insulin sensitivity and secretion. MATERIAL AND METHODS The CA microsatellite and SNPs were genotyped in 389 type 2 diabetes mellitus (T2DM) patients. A 75 g oral glucose tolerance test (OGTT) was given to all the participants. Associations of the genotypes and haplotypes with insulin sensitivity, insulin secretion, glucose tolerance, and insulin-like growth factor 1 (IGF1) were analyzed by ANCOVA (general linear model) and multiple linear regression, after controlling for gender, age, and BMI. RESULTS The CA microsatellite, rs35767 polymorphisms, and SNP haplotypes with or without CA showed no significant association with metabolic parameters. The C allele of rs5742612 was found to be associated with decreased insulin sensitivity (HOMA-S index, ?=-0.131, P=0.008; fasting insulin level, ?=0.022, P=0.006) and increased insulin secretion (HOMA-B index, ?=0.099, P=0.008; insulin AUC, ?=0.112, P=0.012). The linear regression model also indicated that the A allele of rs2288377 was associated with decreased insulin sensitivity (HOMA-S index, ?=-0.159, P=0.001; fasting insulin, ?=0.143, P=0.001) and increased insulin secretion (HOMA-B index, ?=0.114, P=0.017; insulin AUC, ?=0.042, P=0.002). CONCLUSIONS The CA microsatellite and rs35767 have no genotype-related difference in insulin sensitivity or secretion. The rs5742612 and rs2288377 polymorphisms are significantly associated with insulin biology, with the TT genotype exhibiting higher insulin sensitivity and lower insulin secretion compared with carriers of the C allele and A allele, respectively, mostly attributed to the direct functional roles of the two loci.
Project description:Insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3) are members of the insulin-like growth factor (IGF) family that play important roles in carcinogenesis. We hypothesized that the functional polymorphisms in IGF-I and IGFBP-3 may be associated with the risk of prostate cancer (PCa) in the Chinese population. This hospital-based case-control study included 664 PCa patients and 702 cancer-free controls. Nine SNPs in IGF-I and IGFBP-3 were genotyped using the TaqMan assay. The genetic associations between the pathogenesis and progression of PCa were assessed by logistic regression. We found that the genotype and allele frequency distribution of rs6218, rs35767 and rs5742612 were significantly different when comparing PCa cases to controls (P ?= 0.005, 0.005 and 0.020, respectively). In the combined analysis, individuals with 2-6 risk alleles had an elevated risk of PCa compared to those with 0-1 risk alleles. We also found that the association between the combined risk alleles and the risk of PCa appeared stronger in the following subgroups: individuals older than 71 years of age (OR ?= 1.41, 95%CI ?= 1.05-1.91, P ?= 0.020), nonsmokers (OR ?= 1.68, 95%CI ?= 1.21-2.32, P ?= 0.002), nondrinkers (OR ?= 1.32, 95%CI ?= 1.02-1.61, P ?= 0.002), and those with a negative family history of PCa (OR ?= 1.28, 95%CI ?= 1.02-1.71, P ?= 0.022). Our results indicate that the three SNPs (rs6218, rs35767 and rs5742612) and the joint genotypes with 2-6 risk alleles, may contribute to the susceptibility to PCa, but not the progression, in the Chinese population.
Project description:Osteoporosis is a polygenic disorder that is determined by the effects of several genes, each with relatively modest effects on bone mass. The aim of this study was to determine whether the vitamin D receptor single nucleotide polymorphism BsmI is associated with bone mineral density (BMD) in Spanish postmenopausal women. A total of 210 unrelated healthy postmenopausal women aged 60 ± 8 years were genotyped using TaqMan(®) SNP Genotyping Assays. Lumbar and femoral BMD were determined by dual-energy X-ray absorptiometry (DEXA). Daily calcium and vitamin D intake were determined by a food questionnaire. No differences were found in the femoral neck, trochanter, Ward's Triangle, L2, L3, L4, L2-L4, or between the femoral neck and total hip BMD after further adjustment for potential confounding factors (P > 0.05) (age, BMI, years since menopause and daily calcium intake). The BsmI polymorphism in the VDR gene was not associated with BMD in Spanish postmenopausal women.
Project description:Determining how quickly bisphosphonate treatment effects begin to regress is crucial when considering termination of treatment.Our objective was to assess the effects of 1 yr discontinuation of risedronate use in postmenopausal women with osteoporosis who had previously received risedronate for 2 or 7 yr.Before initiation of the current study, placebo/5-mg-risedronate patients had received placebo for 5 yr and risedronate for 2 yr, whereas 5-mg-risedronate patients had received risedronate for a total of 7 yr. Risedronate was then discontinued for 1 yr (yr 8).Postmenopausal women with osteoporosis who had previously completed the 3-yr Vertebral Efficacy with Risedronate Therapy MultiNational (VERT-MN) pivotal trial, plus a 2-yr extension comparing risedronate or placebo for a total of 5 yr, followed by 2 yr of open-label risedronate treatment were enrolled in these trial extensions.Evaluations included changes in type I collagen cross-linked N-telopeptide (NTX)/creatinine (Cr) and bone mineral density (BMD) values, fracture incidence, and adverse events.After 1 yr of risedronate discontinuation, NTX/Cr levels increased toward baseline in both patient groups vs. the values at the end of yr 7. In both treatment groups, off-treatment total hip and femoral trochanter BMD values decreased, whereas lumbar spine and femoral neck BMD were maintained or slightly increased. The adverse event profiles were similar between the two treatment groups during yr 8.One year of discontinuation of risedronate treatment in patients who had received 2 or 7 yr of risedronate therapy led to increases in NTX/Cr levels toward baseline and decreases in femoral trochanter and total hip BMD.
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:The correlation of genetic polymorphisms of GALNT3 and vitamin D receptor (VDR) with osteoporosis in postmenopausal women was investigated. A total of 1,212 cases of postmenopausal patients diagnosed with osteoporosis (observation group) and 404 cases of postmenopausal women without osteoporosis (control group) were selected. Dual-energy X-ray absorptiometry was used for measurement of bone mineral density (BMD) of lumbar vertebrae L2-4, proximal femoral neck and total hip, and classifications were made. TaqMan genotyping technology was employed to examine tag single-nucleotide polymorphism (tagSNP) of GALNT3 and VDR and the correlation of tagSNP with bone turnover markers (BTMs) and serum calcium and phosphorous levels was analyzed. The multiple logistic regression analysis was used to screen risk factors for osteoporosis. A comparison of age and menopause time of the two groups, yielded no statistical significance difference (P>0.05). BMD and T values of the lumbar vertebrae, femoral neck and total hip in the observation group were significantly lower than those in the control group, and the differences were statistically significant (P<0.05). A comparison of the degree of osteoporosis, yielded statistically significant differences (P<0.05). The proportion of tagSNP of 5 loci in GALNT3 and 3 loci in VDR in the observation group was significantly higher than that in the control group, and the differences were of statistical significance (P<0.05). Levels of 25-OHD3, ?-CTX, P1NP and serum calcium in the observation group were lower than those in the control group and the level of serum phosphorus in the observation group was higher than that in the control group, and all of these results were statistically significant (P<0.05). The result of the correlation analysis revealed that rs1425000 and rs757343 were negatively correlated with BTM and serum calcium and phosphorus levels (P<0.05). The result of the regression analysis revealed that 8 tagSNPs were independent risk factors for osteoporosis. Genetic polymorphisms of GALNT3 and VDR were closely associated with osteoporosis in postmenopausal women.
Project description:Postmenopausal osteoporosis (PMOP) is a major global public health concern and older women are more susceptible to experiencing fragility fractures. Our study investigated the associations between circulating proteins with bone mineral density (BMD) in postmenopausal women with or without low BMD (osteoporosis and osteopenia) to explore the pathogenesis of PMOP and discover novel biomarkers for this disease..