Association of the insulin-like growth factor-1 single nucleotide polymorphisms rs35767, rs2288377, and rs5742612 with osteoporosis risk: A meta-analysis.
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ABSTRACT:
SUBMITTER: Chen YC
PROVIDER: S-EPMC5758177 | biostudies-literature | 2017 Dec
REPOSITORIES: biostudies-literature
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Association of the insulin-like growth factor-1 single nucleotide polymorphisms rs35767, rs2288377, and rs5742612 with osteoporosis risk: A meta-analysis.
Chen Ying-Chun YC Zhang Lin L Li Er-Nan EN Ding Li-Xiang LX Zhang Gen-Ai GA Hou Yu Y Yuan Wei W
Medicine 20171201 51
<h4>Background</h4>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.<h4>Methods</h4>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 calc ...[more]
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Project description:BackgroundSeveral studies have been conducted on the relationship between insulin-like growth factor 1 gene (IGF-1) rs35767 polymorphisms and cancer risk, but the results are conflicting. We performed a meta-analysis to investigate the relationship between IGF-1 rs35767 polymorphisms and cancer risk.MethodsEight studies (5 for IGF-1 rs35767 C>T and 3 for IGF-1 rs35767 A>G) with a total of 11,257 cases and 16,213 controls were included. The studies were about the association between IGF-1 rs35767 polymorphisms and cancer risk and acquired by searching PubMed, Embase, and Web of Science databases for articles published before January 20, 2019. STATA software was used to analyze the data and identify the strength of the association by using pooled-odds ratios (ORs) with corresponding 95% confidence intervals (CIs).ResultsNo significant associations were observed between the IGF-1 rs35767 C>T polymorphism and cancer risk in all genetic models. However, the IGF-1 rs35767 A>G polymorphism was significantly associated with increased cancer risk for all genetic models (G vs A: OR = 1.087, 95% CI: 1.036-1.141, Ph = .338; GG vs AA: OR = 1.272, 95% CI: 1.121-1.442, Ph = .359; AG vs AA: OR = 1.187, 95% CI: 1.043-1.351, Ph = .695; AG+GG vs AA: OR = 1.187, 95% CI: 1.043-1.351, Ph = .695; GG vs AA+AG: OR = 1.086, 95% CI: 1.025-1.151, Ph = .275). Begg and Egger tests showed that no publication bias existed.ConclusionOur findings indicated that the IGF-1 rs35767 A>G polymorphism might be a risk factor for cancer development. However, additional well-designed studies with sample sizes larger than ours need to be conducted in the future to verify our findings.
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Project description:Background: Insulin-like growth factor-1 (IGF-1) has been demonstrated to increase fatty acid β oxidation during fasting, and play an important role in regulating lipid metabolism and type 2 diabetes mellitus (T2DM). The rs35767 (T > C) polymorphism, a functional SNP was found in IGF-1 promoter, which may directly affect IGF-1 expression. However, the inconsistent findings showed on the IGF-1 rs35767 polymorphism and T2DM risk. Methods: We performed a comprehensive meta-analysis to estimate the association between the IGF-1 rs35767 and T2DM risk among four genetic models (the allele, additive, recessive and dominant models). Results: A total 49,587 T2DM cases and 97,906 NDM controls were included in the allele model, a total 2256 T2DM cases and 2228 NDM controls were included in the other three genetic models (the additive; recessive and dominant models). In overall analysis, the IGF-1 rs35767 was shown to be significantly associated with increased T2DM risk for the allele model (T vs. C: OR = 1.251, 95% CI: 1.082-1.447, p = 0.002), additive model (homozygote comparisons: TT vs. CC: OR = 2.433, 95% CI: 1.095-5.405, p = 0.029; heterozygote comparisons: TC vs. CC: OR = 1.623, 95% CI: 1.055-2.495, p = 0.027) and dominant model (TT + CT vs. CC: OR = 1.934, 95% CI: 1.148-3.257, p = 0.013) with random effects model. After omitting Gouda's study could reduce the heterogeneity, especially in the recessive model (TT vs. CC + CT: I2 = 38.7%, p = 0.163), the fixed effects model for recessive effect of the T allele (TT vs. CC + CT) produce results that were of borderline statistical significance (OR = 1.206, 95% CI: 1.004-1.448, p = 0.045). And increasing the risk of T2DM in Uyghur population of subgroup for the allele model. Conclusion: The initial analyses that included all studies showed statistically significant associations between the rs35767 SNP and type 2 diabetes, but after removing the Gouda et al. study produced results that were mostly not statistically significant. Therefore, there is not enough evidence from the results of the meta-analysis to indicate that the rs35767 SNP has a statistically significant association with type 2 diabetes.
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Project description:Aim of the studyTo analyze six single nucleotide polymorphisms (SNPs): rs1520220, rs2945834, rs5747694, rs6214, rs6219, rs5742678. An attempt was made to assess the significance of the above IGF-1 gene polymorphisms as prognostic and predictive factors in Polish women with diagnosed increased breast mammographic density.Material and methodsThe study included women diagnosed with an increased breast mammographic density (n = 98), breast cancer (n = 135) and women as a control group (n = 60). The method used to detect polymorphisms in the IGF-1 gene was the analysis of single-stranded DNA conformation polymorphism (SSCP-PCR) and Sanger's sequencing.ResultsIn the case of rs1520220 polymorphism, the genotype CC was found to increase the risk of breast cancer (OR = 2.6 95% CI 1.01-6.5, p = 0.04). Analysis of the rs2945834 polymorphism revealed that the occurrence of the G allele reduced the risk of breast cancer, while the occurrence of the A allele increased the risk of disease almost twice (OR = 0.55 95% CI). Among women who are heterozygous in terms of rs5747694 polymorphism (TG), the risk of breast cancer is twice as high as in the control group. The SNPs in the study group did not correlate with mammographic breast density.ConclusionsThe results obtained in the course of the analysis indicate that polymorphisms rs1520220, rs2946834, rs5747694 gene IGF-1 are associated with the occurrence of breast cancer but not with increased mammographic density. Summing up, the association between the polymorphisms of IGF-1 and the risk of developing breast cancer is independent of mammographic density.
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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, β=-0.131, P=0.008; fasting insulin level, β=0.022, P=0.006) and increased insulin secretion (HOMA-B index, β=0.099, P=0.008; insulin AUC, β=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, β=-0.159, P=0.001; fasting insulin, β=0.143, P=0.001) and increased insulin secretion (HOMA-B index, β=0.114, P=0.017; insulin AUC, β=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.
| S-EPMC5549718 | biostudies-literature
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.
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Project description:ObjectiveADAM12 polymorphisms may be associated with the risk of knee osteoarthritis (KOA), but currently available evidence remains controversial. We performed this meta-analysis to confirm whether ADAM12 polymorphisms were associated with susceptibility of KOA.MethodsA comprehensive literature search in PubMed, EMBASE, and ISI Web of Science was conducted to identify observational studies assessing the association between ADAM12 polymorphisms and susceptibility of KOA. The strength of association was indicated as odds ratio (OR) and the corresponding 95% confidence interval (95%CI). Four types of genetic model (additive model, dominant model, recessive model, and allele model) were evaluated for each included study. Subgroup analysis by ethnicity was performed.ResultsSeven case-control studies comprising a total of 3512 KOA patients and 5405 healthy controls were included in the meta-analysis. A significant association between rs1871054 and increased KOA risk was found in each genetic model. No significant association was found between KOA and rs3740199, rs1044122, or rs1278279 in any genetic model.ConclusionBased on the findings of our study, there was a modest but statistically significant association between rs1871054 and risk of KOA in Asian population, while other polymorphisms (rs3740199, rs1044122, or rs1278279) in ADAM12 were not associated with KOA in any population.
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Project description:Genetic risk factors for osteoporosis, a prevalent disease associated with aging, have been examined in many genome-wide association studies (GWASs). A major challenge is to prioritize transcription-regulatory GWAS-derived variants that are likely to be functional. Given the critical role of epigenetics in gene regulation, we have used an unusual epigenetics-based and transcription-based approach to identify some of the credible regulatory single-nucleotide polymorphisms (SNPs) relevant to osteoporosis from 38 reported bone mineral density (BMD) GWASs. Using Roadmap databases, we prioritized SNPs based upon their overlap with strong enhancer or promoter chromatin preferentially in osteoblasts relative to 12 heterologous cell culture types. We also required that these SNPs overlap open chromatin (Deoxyribonuclease I [DNaseI]-hypersensitive sites) and DNA sequences predicted to bind to osteoblast-relevant transcription factors in an allele-specific manner. From >50,000 GWAS-derived SNPs, we identified 14 novel and credible regulatory SNPs (Tier-1 SNPs) for osteoporosis risk. Their associated genes, BICC1, LGR4, DAAM2, NPR3, or HMGA2, are involved in osteoblastogenesis or bone homeostasis and regulate cell signaling or enhancer function. Four of these genes are preferentially expressed in osteoblasts. BICC1, LGR4, and DAAM2 play important roles in canonical Wnt signaling, a pathway critical for bone formation and repair. The transcription factors predicted to bind to the Tier-1 SNP-containing DNA sequences also have bone-related functions. We present evidence that some of the Tier-1 SNPs exert their effects on BMD risk indirectly through little-studied long noncoding RNA (lncRNA) genes, which may, in turn, control the nearby bone-related protein-encoding gene. Our study illustrates a method to identify novel BMD-related causal regulatory SNPs for future study and to prioritize candidate regulatory GWAS-derived SNPs, in general. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
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Project description:ObjectiveTo evaluate the association of insulin-like growth factor 1 gene rs12423791 and rs6214 polymorphisms with high myopia.MethodsAn electronic search was conducted on PubMed, Embase, the Cochrane Library and the Chinese Biological Abstract Database for articles published prior to May 6, 2014. A meta-analysis was performed using Revman 5.1 and Stata 12.0, and the odds ratios with 95% confidence intervals were calculated in fixed or random effects models based on the results of the Q test. The subgroup analysis was conducted on the basis of the various regions, the sensitivity analysis was also performed to evaluate the stability of the results, and the publication bias was evaluated by a funnel plot and Egger's linear regression analysis.ResultsThis comprehensive meta-analysis included 2808 high myopia patients and 2778 controls from five unrelated studies. The results demonstrated that the significant association was not present in any genetic models between IGF-1 rs12423791 or rs6214 and high myopia. However, subgroup analysis indicated that rs12423791 polymorphism was associated with high myopia in the Chinese populations in the allelic contrast model (C vs. G: OR=1.24, 95% CI=1.04-1.48 in the fixed-effects model), the dominant model (CC+CG vs. GG: OR=1.40, 95% CI=1.16-1.69 in the fixed-effects model), and the codominant model (CG vs. GG: OR=1.37, 95% CI= 1.12-1.68 in the fixed-effects model). Additionally, none of the individual studies significantly affected the association between IGF-1 rs12423791 and high myopia, according to sensitivity analysis.ConclusionThis meta-analysis shows that IGF-1 rs12423791 or rs6214 gene polymorphism is not associated with high myopia.
| S-EPMC4468052 | biostudies-literature