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Comparisons of the baseline levels of FPG (a) and PPG (b) in T2DM patients with different IGF2BP2 gene rs4402960 genotypes. Data are means ± SD. * p < 0.05, ** p < 0.01, compared with the GG genotype (n = 281).
Source publication
Background:
Genome-wide association studies identified that insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) genetic polymorphisms are related to type 2 diabetes mellitus (T2DM) in several populations. This study aimed to investigate whether the IGF2BP2 gene rs1470579 and rs4402960 polymorphisms were associated with T2DM and pioglitaz...
Citations
... The genes involved in glucose transport, blood glucose homeostasis, beta cell function, insulin secretion, and pancreatic developmental pathways are considered to be excellent candidates in T2D ethology (7)(8)(9)(10). The IGF2BP2 gene has been implicated in pancreatic β-cell dysfunction, decreased insulin secretion and activation leading to the development of T2D (10)(11)(12)(13). ...
... The IGF2BP2 gene modulates the translation of IGF2 by binding to the 5'-untranslated region of IGF2 mRNA (11)(12)(13). The IGF2BP2 gene is located in the q27.2 region of chromosome 3 and has important functions in RNA trafficking, stability and translation (13,14). ...
... SNPs in this intron are thought to affect gene function through possible mechanisms by alternative splicing, protein interaction of IGF2BP2, miRNAs or antisense mRNA transcription, regulation of large noncoding transcription factors. Many genes located near IGF2BP2 are metabolic regulators involved in insulin metabolism (11)(12)(13)(14). SNPs may also be directly associated with miRNAs, non-coding transcripts and close variants affecting antisense mRNAs transcribed in intron 2 (11). ...
Background/Aims: Type 2 diabetes (T2D) whose prevalance differs in different populations is a multifactorial disease. T2D is describes a group of clinical syndromes resulting from glucose metabolism disorders triggered by genetic or environmental factors. Insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) gene participates in insulin signaling pathway and is involved in insulin secretion. SNPs in one of these genes, IGF2BP2 gene (rs1470579 and rs4402960), have been reported to partially increase the risk of type II diabetes. The aim of this study was to investigate in a Turkish population identified associations of IGF2BP2 variants rs4402960 and rs1470579 with T2D. Methods: We genotyped two SNPs of IGF2BP2 gene, rs1470579 and rs4402960 in 100 healthy individuals and 100 patients. DNA isolation was performed on peripheral blood samples from patients and healthy groups. The molecular analysis of rs1470579 and rs4402960 polymorphisms of IGF2BP2 gene of each individual was performed by using Real-Time PCR (Applied Biosystems) method. Relationships of genotypes and alleles frequency of IGF2BP2 polymorphisms and T2D were examined by "Chi-square" or "Likelihood ratio" tests. Results: As a result of the genotype and allele distributions; there was association between type II diabetes patients and control group for IGF2BP2 rs1470579 (A/C) gene polymorphism (p=0.0123). The frequency of AC genotype in patients is more than the control group. However, there was no statistically significant difference genotype distribution between the type 2 diabetes patients and control group for IGF2BP2 rs4402960 (G/T) gene polymorphisms. There was no association between the patients and the control group for TT and GG+GT genotype distribution (p=0.8847). Conclusions: The results showed that the IGF2BP2 gene rs1470579 and rs4402960 polymorphisms were associated with T2D in a Turkish population (OR = 2.002, 95% CI 1.170–3.426, p < 0.05; OR = 1.879, 95% CI 1.110–3.182, p< 0.05). This is the first study between IGF2BP2 gene polymorphisms and type II diabetes in Turkish population. Keywords: IGF2BP2, T2D, Polymorphism
... CHARLS is a national survey in middle to older aged adults in China (aged 45 years and above) that attempts to provide a wealth of information ranging from socio-economic status to health conditions. The survey informs scientific research and priority setting related to the middle-aged and older adult population in China (14,15). ...
... The whole blood count was performed immediately at the survey sites. The whole blood samples were then stored at 4 degrees Celsius, and the remaining samples were transported to the central Laboratory in Beijing Youanmen Centre for Clinical Laboratory of Capital Medical University for further laboratory analysis (14,15). The levels of blood glucose, total cholesterol (TC), TG, low density lipoprotein (LDL-C) and high density lipoprotein (HDL-C) were tested by enzyme colorimetry. ...
Background
Lipid accumulation product (LAP), a product of waist circumference (WC) and fasting triglycerides (TG), is a measure of lipid accumulation and an effective predictor of metabolic syndrome. This study aimed to evaluate the associations of LAP and its longitudinal transitions with type 2 diabetes mellitus (T2DM) among middle-aged and older Chinese.
Methods
Data were extracted from the China Health and Retirement Longitudinal Study (2011, 2013, 2015, and 2018). LAP was defined as (WC-65) ×TG for men, and (WC-58) ×TG for women. Participants were classified into high- and low-LAP groups at baseline, and subsequently into four transition patterns during 2011-2015: maintained-high, maintained-low, high-to-low, and low-to-high LAP. The longitudinal transition patterns of LAP on the development of T2DM were assessed by multivariable Cox frailty models.
Results
Overall, 7397 participants were included for analysis, among whom 849 (11.5%) developed T2DM between 2011 and 2018. Women with high-LAP levels at baseline presented a higher risk of T2DM (hazard ratios [HR]=1.37, 95% confidence interval [CI]: 1.07-1.77), while no significant association was found in men. Compared with women with maintained-low LAP pattern, those with transition patterns of low-to-high LAP and maintained-high LAP were at higher risk of T2DM (HR =1.99 and 1.98, both P <0.05); however, for men, the significantly positive association was only observed in maintained-high LAP transition pattern (HR=1.53, 95% CI: 1.04-2.23).
Conclusions
Elevated LAP levels and the transition patterns of maintained-high LAP and low-to-high LAP are significant risk factors for T2DM in women. Preventions are needed to combat T2DM at an early dyslipidemic stage.
... IGF2BP2 rs4402960 and rs1470579 are the most common SNPs in diabetes. Research shows that expressions of IGF2BP2 rs4402960 gene variant in Chinese Han [27][28][29][30][31], Japanese [32], Asian [27,33], Icelandic [34], Greek-Cypriot [35], Czechs [26], Germania [33,36], Lebanese [37], Arabian [38], Tunisian [39], Moroccan [38] and Indian population [40] increase the risk for T2D. IGF2BP2 rs4402960 is also associated with lower fasting insulin level and impaired β-cell function, both associated with obesity [34]. ...
... In addition, the therapeutic efficacy of repaglinide is enhanced in Chinese T2D patients with IGF2BP2 rs4402960 polymorphism [41]. The effect of pioglitazone on postprandial plasma glucose, glycated hemoglobin, serum triglycerides and high-density lipoprotein cholesterol is in Chinese individuals with rs4402960 polymorphism [30]. Moreover, IGF2BP2 rs4402960 is strongly associated with the development of gestational diabetes mellitus (GDM), besides being a potential diagnostic marker for GDM as well [42]. ...
... On the other hand, IGF2BP2 rs1470579 is also associated with T2D in Lebanese [45], Chinese Han [29,30] and Iranian populations [46]. In addition, IGF2BP2 rs1470579 polymorphism reduces the therapeutic efficacy of repaglinide in T2D patients in Chinese population [41]. ...
The human insulin-like growth factor 2 (IGF2) mRNA binding proteins 2 (IGF2BP2/IMP2) is an RNA-binding protein that regulates multiple biological processes. Previously, IGF2BP2 was thought to be a type 2 diabetes (T2D)-associated gene. Indeed IGF2BP2 modulates cellular metabolism in human metabolic diseases such as diabetes, obesity and fatty liver through post-transcriptional regulation of numerous genes in multiple cell types. Emerging evidence shows that IGF2BP2 is an N6-methyladenosine (m6A) reader that participates in the development and progression of cancers by communicating with different RNAs such as microRNAs (miRNAs), messenger RNAs (mRNAs) and long non-coding RNAs (lncRNAs). Additionally, IGF2BP2 is an independent prognostic factor for multiple cancer types. In this review, we summarize the current knowledge on IGF2BP2 with regard to diverse human metabolic diseases and its potential for cancer prognosis.
... Liu et al. revealed that those with the rs4402960 GT+TT genotype or T allele gene had significantly increased susceptibility to breast cancer [23]. Zhang et al. and Huang et al. found that those with the IGF2BP2 rs4402960 T allele had higher risk of T2D, and this polymorphism may also influence therapeutic effects in those of Chinese ethnicity [24,25]. However, due to the lack of information about diabetes mellitus status in our oral cancer patient group, the relationships between IGF2BP2 SNPs and diabetes mellitus in oral cancer patients should be further addressed in the future. ...
Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) is associated with insulin resistance, lipid metabolism, and tumorigenesis. However, the association between the IGF2BP2 polymorphism and oral cancer risk remains unclear. We recruited 1349 male patients with oral cancer and 1198 cancer-free controls. Three single nucleotide polymorphisms IGF2BP2 rs11705701, rs4402960, and rs1470579 were assessed using real-time polymerase chain reaction. The results indicate that the male patients with oral cancer and with the rs11705701 GA+AA, rs4402960 GT+TT, and rs1470579 AC+CC genotypes had increased risk of advanced clinical stage, larger tumor, and progression of lymph node metastasis compared with those with wild-type IGF2BP2. Moreover, according to The Cancer Genome Atlas dataset, high expression of the IGF2BP2 gene is associated with poor survival in patients with head and neck squamous cell carcinoma. In conclusion, our results suggest that IGF2BP2 polymorphisms are associated with less favorable oral cancer clinical characteristics.
... 29 Several case-control studies assessed the potential association of IGF2BP2 rs1470579 A > C variants with T2DM susceptibility and therapeutic efficacy in the Chinese population. 30,31 In these studies, IGF2BP2 rs1470579 A > C polymorphism were found to be associated with T2DM risk, and this polymorphism may influence the therapeutic efficacy of some oral antidiabetic agents in patients with T2DM. 30,31 It is found that some variants in energy metabolism-related gene may influence the development of cancer. ...
... 30,31 In these studies, IGF2BP2 rs1470579 A > C polymorphism were found to be associated with T2DM risk, and this polymorphism may influence the therapeutic efficacy of some oral antidiabetic agents in patients with T2DM. 30,31 It is found that some variants in energy metabolism-related gene may influence the development of cancer. 22,23,32 In the current study, we first explored the association of IGF2BP2 rs1470579 A > C polymorphism with the risk of EGJA. ...
Esophagogastric junction adenocarcinoma (EGJA) may be associated with obesity and overweight. Thus, any variant in energy metabolism–related gene may influence the development of EGJA. In this study, we recruited 720 EGJA cases and 1541 noncancer controls. We selected IGF2BP2 rs4402960 G > T, rs1470579 A > C, IGF1 rs5742612 A > G and IGFBP3 rs3110697 G > A, rs2270628 C > T and rs6953668 G > A loci and assessed the relationship of these polymorphisms with lymph node status and susceptibility of EGJA. We found that IGF2BP2 rs1470579 A > C and IGFBP3 rs6953668 G > A polymorphisms were associated with the decreased risk of EGJA ( IGF2BP2 rs1470579: CC vs AA: adjusted odds ratio [OR] = 0.65, 95% confidence interval [CI] = 0.43‐0.98, P = 0.041 and CC vs AA/AC: adjusted OR = 0.62, 95% CI = 0.41‐0.93, P = 0.021 and IGFBP3 rs6953668: GA vs GG: adjusted OR = 0.66, 95% CI = 0.47‐0.93, P = 0.019 and GA/AA vs GG: adjusted OR = 0.68, 95% CI = 0.48‐0.95, P = 0.026). However, we also found that IGF1 rs5742612 A > G polymorphism increased the risk of LNM among patients with EGJA (GG vs AA: adjusted OR = 1.88, 95% CI = 1.02‐3.46, P = 0.042 and GG vs AA/AG: adjusted OR = 1.92, 95% CI = 1.06‐3.47, P = 0.032). This study suggests that IGF2BP2 rs1470579 A > C and IGFBP3 rs6953668 G > A polymorphisms may decrease genetic susceptibility to EGJA in eastern Chinese Han population. In addition, our findings also indicate that IGF1 rs5742612 A > G polymorphism may increase the susceptibility of LNM among patients with EGJA.
... 33 Several case-control studies reported that IGF2BP2 rs4402960 G>T polymorphism was associated with the risk of T2DM and might affect the therapeutic efficacy of antidiabetic in Chinese population. 34,35 We found that the IGF2BP2 rs4402960 TT genotype was associated with the decreased susceptibility of NSCLC among female, years, and never drinking patients. Previous report showed that IGF2BP2 rs4402960 G>T polymorphism was associated with the increased risk of breast cancer in a Chinese population. ...
Background
IGF2BP2 and IGFBP3 polymorphisms may be associated with cancer risk.
Methods
With an aim to determine the association of variations in IGF2BP2 and IGFBP3 genes with risk of non-small-cell lung cancer (NSCLC), IGF2BP2 rs1470579 A>C, rs4402960 G>T and IGFBP3 rs2270628 C>T, rs3110697 G>A, and rs6953668 G>A polymorphisms were selected and genotyped in 521 NSCLC patients and 1,030 controls.
Results
We found that there was no difference in IGF2BP2 and IGFBP3 genotype distribution among the NSCLC patients and controls. The stratified analyses suggested that IGF2BP2 rs1470579 A>C polymorphism decreased the risk of NSCLC in some subgroups (female subgroup: CC vs AA: adjusted P=0.032 and CC vs AC/AA: adjusted P=0.028; <60 years subgroup: CC vs AA: adjusted P=0.012 and CC vs AC/AA: adjusted P=0.013; and never drinking subgroup: CC vs AA: adjusted P=0.046 and CC vs AC/AA: adjusted P=0.031). The stratified analyses also found that IGF2BP2 rs4402960 G>T polymorphism decreased the risk of NSCLC in some subgroups (female subgroup: TT vs GG: adjusted P=0.031 and TT vs GT/GG: adjusted P=0.026; <60 subgroup: TT vs GG: adjusted P=0.037 and TT vs GT/GG: adjusted P=0.038; and never drinking subgroup: TT vs GT/GG: adjusted P=0.046). Haplotype analysis indicated Ars1470579Crs2270628Grs3110697Grs4402960Ars6953668 haplotype decreased susceptibility of NSCLC (P=0.007).
Conclusion
Our study suggests that IGF2BP2 rs1470579 A>C, rs4402960 G>T single-nucleotide polymorphisms are candidates for decreased susceptibility to NSCLC among female, <60 years, and never drinking subgroups. In the future, more case–control studies with functional analysis are needed to confirm these preliminary findings.
... Metformin, a biguanide derivate, has pleiotropic effects beyond glucose reduction, including improvement of lipid profiles and reduction microvascular and macrovascular complications associated with T2DM [8]. Pioglitazone, a new thiazolidinedione, is widely to treat T2DM [9] and has been associated with redistribution of body fat, which can predict insulin resistance and adverse drug-related events in patients [10]. Rosiglitazone is an oral hypoglycaemic agent of the thiazolidinedione group that improves plasminogen activity and high-density lipoprotein cholesterol levels in T2DM [11]. ...
We performed a network meta-analysis to compare the efficacy of 12 single-drug regimens (Glibenclamide, Glimepiride, Pioglitazone, Rosiglitazone, Repaglinide, Metformin, Sitaglitin, Exenatide, Liraglutide, Acarbose, Benfluorex, and Glipizide) in the treatment of type 2 diabetes mellitus (T2DM). Fifteen relevant randomized controlled trials (RCTs) were included; direct and indirect evidence from these studies was combined, and weighted mean difference (WMD) and surface under the cumulative ranking curves (SUCRAs) were examined to evaluate the monotherapies. Liraglutide was more effective than Glimepiride, Pioglitazone, Sitaglitin, Exenatide, and Glipizide at reducing glycated hemoglobin (HbA1c) levels. In contrast, Acarbose was less effective than Glibenclamide, Glimepiride, Pioglitazone, Rosiglitazone, Repaglinide, Metformin, and Liraglutide at decreasing HbA1c levels. Reductions in fasting plasma glucose (FPG) levels were similar after all treatments. Rosiglitazone was less effective than Glibenclamide and Repaglinide at reducing total cholesterol (TC) levels. High density lipoprotein (HDL), low density lipoprotein (LDL), and triglyceride levels did not differ after treatment with any of the monotherapies. HbA1c and FPG SUCRA values were highest for Liraglutide, while HbA1c and FPG values were lowest for Acarbose, and TC and LDL values were lowest for Rosiglitazone. These results suggest that Liraglutide may be most effective, and Acarbose least effective, at reducing blood glucose levels, while Glibenclamide, Repaglinide, and Metformin may be most effective, and Rosiglitazone least effective, at reducing lipoidemia, in T2DM patients.
... Diabetes is a systemic disease that can cause a range of complications, which can affect the structure and function of the central nervous system through different stages, and their effects may overlap and magnify [1]. Diabetesassociated cognitive decline (DACD) is not caused by only one factor, but the multi-factor and multi-link complex pathological changes [2]. ...
Our present investigation aimed to determine the neuroprotection of apigenin (API) against diabetes-associated cognitive decline (DACD) a diabetic rat model and exploring its potential mechanism. Diabetic rat model was induced by intraperitoneal injection of streptozotocin. All experiment animals treated with vehicle or API by doses of 10, 20 and 40 mg/kg for seven weeks. Firstly, the body weight and blood glucose levels were detected. We used Morris water maze test to evaluate learning and memory function. The oxidative indicators (malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH)), cNOS, iNOS, caspase-3 and caspase-9 were measured in cerebral cortex and hippocampus using corresponding commercial kits. API can increase body weight, reduce the blood glucose levels, and improve the cognitive function in rats induced by diabetes. API decrease the MDA content, and increase SOD activity and GSH level of diabetic animals in the cerebral cortex and hippocampus of diabetic rats. Meanwhile, constitutive nitric oxide synthase (cNOS), inducible nitric oxide synthase (iNOS), caspase-3/9 were markedly exhibited in the cerebral cortex and hippocampus of diabetic rats. In summary, our current work discloses that API attenuates DACD in rats via suppressing oxidative stress, nitric oxide and apoptotic cascades synthase pathway.
... In a study by Grarup et al [14], it was found that the risk-allele (T) carriers of rs4402960 had reduced acute insulin secretion following glucose challenge and tolbutamide stimulation in young healthy Danish subjects. Several studies in other populations reported that IGF2BP2 rs4402960 polymorphism was also associated with lower fasting insulin concentration, decreased disposition index, and early-or first-phase insulin secretion [36][37][38][39][40]. IGF2BP2 rs4402960 and rs1470579 polymorphisms were also reported to be associated with elevated fasting glucose level [41]. Thus, it was hypothesized that IGF2BP2 polymorphisms may mediate their role in T2DM pathogenesis through modulating islet beta-cell function [27]. ...
Genome-wide association studies identified novel genes associated with T2DM which have been replicated in different ethnic populations and yielded inconsistent results. Our study aimed to replicate in Egyptian population the identified association of insulin growth factor 2 m-RNA binding protein 2 (IGF2BP2) genetic variants rs4402960 and rs1470579 with T2DM. Our study included 120 unrelated T2DM patients and 128 control subjects who were genotyped by real-time polymerase chain reaction (real-time PCR). For rs1470579, the variant C allele was associated with T2DM (p<0.001). The frequency of (A/C + C/C) genotypes vs. A/A genotype was significantly higher in T2DM patients than in controls (70% vs. 30% and 37.5% vs. 62.5%, respectively) (p=0.00001). For rs440960, the variant T allele was associated with T2DM (p<0. T2DM patients than in controls (65.5% vs. 34.5% and 37.5% vs. 62.5%, respectively), (p=0.00001). These associations remained significant under all genetic models and after adjustment for covariates: gender, BMI, TGs and HDL-c. Both SNPs were in strong LD (D′ = 0.99 and r 2 =0.98). Taking the common GA haplotype as reference, TC was the most frequent haplotype in T2DM patients and strongly associated with the disease (p = 0.004, OR= 3.29, 95%CI = 2.19–10.84), followed by GC haplotype (p = 0.02, OR=1.42, 95% CI=1.08–1.88) then the TA haplotype (P= 0.04, OR=1.14, 95%CI=0.99–1.86). In conclusion, IGF2BP2 susceptibility variants rs4402960 and rs1470579 associate with T2DM in Egyptians.
