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Role of ADIPOQ SNPs in T2D: The ADIPOQ CGTT, GTTT and GGTG haplotypes in presence of ADIPOQ +10211T/G (rs17846866) and +276G/T (rs1501299) along with decreased transcript, plasma HMW adiponectin and total adiponectin, and increased TNFα, FFA, resistin leads to altered metabolic profile thereby contributing to insulin resistance and T2D in Gujarat population.
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Adiponectin is a prime determinant of the status of insulin resistance. Association studies between adiponectin (ADIPOQ) gene single nucleotide polymorphisms (SNPs) and metabolic diseases have been reported earlier. However, results are ambiguous due to apparent contradictions. Hence, we investigated (1) the association between ADIPOQ SNPs: −11377C...
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Context 1
... were CGTG (p = 0.0003), CGTT (p = 6.32 × 10 −5 ), GGTT (p = 0.0207) and GGTG (p = 0.0030) (Table S4). Furthermore, the GGTG (p = 3.87 × 10 −5 ) haplotype in particular was found to be significantly higher in obese patients as shown in Table 2. The LD analysis revealed that the four SNPs investigated were in low to moderate LD association (Fig. S2). Haplotype and LD analyses were not performed in the J&K population as only −11377C/G (rs266729) was found to be associated with T2D and the genotypes of +10211T/G (rs17846866) were ...
Context 2
... the hypothesis. To summarize, +10211T/G (rs17846866) and +276G/T (rs1501299) are significantly associated with increased FBG, BMI, TG, TC and reduced HMW adiponectin/total adiponectin ratio. More importantly, the haplotype analysis reveals that individuals with GGTG haplotype in particular show an increased tendency towards obesity induced T2D 55 (Fig. 2). Thus, we may conclude that adiponectin gene is associated with T2D, nonetheless variation in the susceptibility loci within the gene depends on ethnic variation among different populations. However, further investigations to understand the mechanistic aspects of genetic variants regulating adiponectin levels are warranted in other ...
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Adiponectin is a prime determinant of the status of insulin resistance. Association studies between adiponectin (ADIPOQ) gene single nucleotide polymorphisms (SNPs) and metabolic diseases have been reported earlier. However, results are ambiguous due to apparent contradictions. Hence, we investigated (1) the association between ADIPOQ SNPs: −11377C...
Citations
... accessed on 10 January 2022) [77]. Two of the SNPs included in the study are located in the 5 ′ flanking region (rs822387, rs860291), two in the gene promoter (rs17300539, rs266729), twelve in introns (rs182052, rs822393, rs822395, rs822396, rs7627128, rs2036373, rs17366568, rs17846866, rs1501299, rs2241767, rs3821799, rs3774261), and two in exons (rs2241766, rs1063539), as shown in Table 2. ADIPOQ genotyping was performed using a polymerase chain reaction-restriction fragment length polymorphism method according to the modified protocols described elsewhere [71,75,[78][79][80][81][82][83][84]. Detailed information on primer sequences, restriction enzymes, and specific product and fragment sizes is listed in Supplementary Table S1. ...
Adiponectin, a hormone secreted by adipose tissue, plays a complex role in regulating metabolic homeostasis and has also garnered attention for its potential involvement in the pathogenesis of late-onset Alzheimer’s disease (LOAD). The objective of this study was to investigate the association of ADIPOQ variants with plasma adiponectin levels and LOAD risk in subjects from the Slovak Caucasian population. For this purpose, 385 LOAD patients and 533 controls without cognitive impairment were recruited and genotyped for a total of eighteen ADIPOQ single nucleotide polymorphisms (SNPs). Both single-locus and haplotype-based logistic regression analyses were employed to assess the association of SNPs with LOAD risk, while linear regression analysis was used to explore their influence on adiponectin levels in LOAD patients. ADIPOQ variants rs822395 and rs2036373 in intron 1 were found to significantly elevate total adiponectin levels after accounting for several potential confounders. Additional SNPs in the 5′ region and intron 1 exhibited a non-significant trend of association with adiponectin. However, none of the ADIPOQ SNPs showed an association with LOAD risk, neither in the whole-group analysis nor in subgroup analyses after stratification for sex or the APOE ε4 allele, a well-established LOAD risk factor. In summary, while adiponectin has emerged as a potential contributor to the development of LOAD, this study did not unveil any significant involvement of its gene variants in susceptibility to the disease.
... In our results, despite differences in the CI for the covariates of hypertension, obesity, and low HDL, such a statistical association was not verified. However, reported ADIPOQ haplotypes that include the T45G and G276T variations, associated with indicators of the MetS, such as type 2 diabetes and obesity, also link their findings with risk factors associated with the disease such as FBG, BMI, and lipid parameters, which suggests its crucial role in susceptibility to metabolic disease [24]. Further research is needed to understand the clinical aspects of genetic variants regulating adiponectin levels in other cohorts. ...
Background and aims
There is a link between genetics with metabolic balance and adiposity homeostasis on metabolic syndrome (MetS). Polymorphism in adipokine genes such as leptin and adiponectin may play an important role in its development. This study aimed to determine the association of the individual and general components of MetS with genetic alterations in LEP (rs7799039 and rs2167270) and ADIPOQ (rs1501299 and rs2241766) genes in the Mexican population.
Methods and results
The polymorphisms of the LEP gene rs7799039 and rs2167270, together with rs1501299 and rs2241766 polymorphisms of the ADIPOQ gene were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) on 328 individuals (n = 131 MetS). The rs7799039 under the recessive inheritance model was found to be associated with increased risk of MetS (OR = 2.16, 95% CI = 1.06–4.37), dyslipidemia (OR = 7.97, 95% CI = 2.17–29.36), low HDL (OR = 7.01, 95% CI = 1.65–29.71) and hypertension (OR = 13.02, 95% CI = 1.76–96.44); the heterozygote demonstrate a protective effect on MetS (OR = 0.48, 95% CI = 0.28–0.88) and diabetes (OR = 0.09, 95% CI = 0.02–0.53) under the over the dominant model. Haplotype analysis showed linkage disequilibrium between the SNPs of ADIPOQ rs1501299/rs2241766, and their association as risk factors for low HDL and hypertension.
Conclusion
The association of rs7799039 with the presence of MetS, suggests a risk factor for the development of dyslipidemia, as well as its heterozygous as a protective factor for DM. There is a linkage disequilibrium between the SNPs of ADIPOQ.
... Several common variants of the ADIPOQ gene are reported in the literature to be associated with obesity, T2DM, and metabolic syndrome, but these results are ethnospecific [39,[41][42][43][44][45]. Three common variants, rs2241766, rs1501299, and rs17366743, were identified in the ADIPOQ gene in our study. ...
... The common intron variant rs1501299 has been associated with Type 2 diabetes in Saudi Arabian and Japanese populations [37]. In the Finnish population, this variant correlated with obesity [44], in the Indian population with low levels of adiponectin [45]. The GG genotype (common G allele) has been associated with favorable changes in adiponectin levels, insulin resistance, and lipid profile after two different dietary interventions [47]. ...
The increase in the prevalence of overweight, obesity and associated diseases is a serious problem. The aim of the study was to identify rare variants in obesity-associated genes in young adults with abdominal obesity in our population and to analyze information about these variants in other populations. Targeted high-throughput sequencing of obesity-associated genes was performed (203 young adults with an abdominal obesity phenotype). In our study, all of the 203 young adults with abdominal obesity had some rare variant in the genes associated with obesity. The widest range of rare and common variants was presented in ADIPOQ, FTO, GLP1R, GHRL, and INS genes. The use of targeted sequencing and clinical criteria makes it possible to identify carriers of rare clinically significant variants in a wide range of obesity-associated genes and to investigate their influence on phenotypic manifestations of abdominal obesity.
... Although adipose tissue was principle wellspring of adiponectin, inquire about discoveries recommend that the blood level of adiponectin is lessened in obese or T2DM who have huge stores of fat tissue [32][33][34][35][36] . Lessening of adiponectin levels has been proposed to assume a focal part in the expanded rate of T2DM and IR disorder [37][38][39][40] . In obese animal models the Adiponectin levels have reduced, which decreases insulin sensitivity and induce DMT2 start 32,[41][42] . ...
Diabetes mellitus caused by insulin resistance is prompted by obesity. Neuropeptide Nesfatin-1 was identified in several organs, including the central nervous system and pancreatic islet cells. Nesfatin-1 peptide appears to be involved in hypothalamic circuits that energy homeostasis and control food intake. Adiponectin is a plasma collagen-like protein produced by adipocytes that have been linked to the development of insulin resistance (IR), diabetes mellitus type 2 (DMT2), and cardiovascular disease (CVD). Resistin was first identified as an adipose tissue–specific hormone that was linked to obesity and diabetes. The aim of this study was to estimate the relationship between human serum nesfatin-1, adiponectin, resistin concentration, and obesity with T2DM. The results show a significant increase in serum neisfatin-1 and resistin levels in the obese diabetic group compared to the non-obese diabetic group. Adiponectin levels had a highly significant decrease in the obese diabetic group compared to the non-obese group and obese control group. Serum Nesfatin-1 and some variables, there was a significant positive correlation with (BMI, insulin, HOMA-IR), and serum resistin had a significant positive correlation with (BMI, WC, TG, insulin, HOMA-IR).On the other hand, there was a negative correlation between serum adiponectin and (BMI, TG, and HOMA-IR). The present results suggest that nesftin-1 may have a role in controlling food intake as well as the development of IR in obese patients.
... Results are reported as a relative expression normalized with the GAPDH housekeeping gene. The fold variation was determined using the 2 −∆∆Ct method according to previously published protocol [17]. ...
Type 2 diabetes (T2D) is associated with obesity and declining β-cells. L-glutamine has been implicated in the amelioration of T2D by virtue of its incretin secretagogue property while, there are mixed reports on pitavastatin’s adiponectin potentiating ability. We aimed to investigate the effect of pitavastatin (P), L-glutamine (LG), and combination (P + LG) on glycemic control and β-cell regeneration in a high-fat diet (HFD) + streptozotocin (STZ)-induced T2D mouse model. C57BL6/J mice treated with HFD + STZ were divided into four groups: diabetes control (HFD + STZ), P, LG, and P + LG, while the control group (NCD) was fed with the normal-chow diet. Significant amelioration was observed in the combination therapy as compared to monotherapies in respect of (i) insulin resistance, glucose intolerance, lipid profile, adiponectin levels, and mitochondrial complexes I, II, and III activities, (ii) reduced phosphoenolpyruvate carboxykinase, glucose 6-phophatase, glycogen phosphorylase, and GLUT2 transcript levels with increased glycogen content in the liver, (iii) restoration of insulin receptor 1β, pAkt/Akt, and AdipoR1 protein levels in skeletal muscle, and (iv) significant increase in islet number due to β-cell regeneration and reduced β-cell death. L-glutamine and pitavastatin in combination can ameliorate T2D by inducing β-cell regeneration and regulating glucose homeostasis.
... The ADIPOQ gene has many variants that result in low adiponectin levels, which correlate with obesity: the rs1391272583 variant in a Brazilian population [52], rs17366568 in a Malaysian population [53], rs266729 in a young Nigerian population [54], variants rs266729, rs16861205, rs1501299, rs3821799, and rs6773957 in a Finnish population [55], and variants rs17846866 and rs1501299 in the Indian population of Gujarat [56]. Other variants in this gene have been associated with type 2 diabetes mellitus (T2DM): rs62625753 and rs17366743 in a French white population [57], rs185847354 in a Japanese population [58], and rs2241766, rs2082940, and rs266729 in a Finnish population [55]. ...
The high prevalence of obesity and of its associated diseases is a major problem worldwide. Genetic predisposition and the influence of environmental factors contribute to the development of obesity. Changes in the structure and functional activity of genes encoding adipocytokines are involved in the predisposition to weight gain and obesity. In this review, variants in genes associated with adipocyte function are examined, as are variants in genes associated with metabolic aberrations and the accompanying disorders in visceral obesity.
... Medical progress in identifying cures and therapies for multi-factorial chronic health disorders like diabetes mellitus (DM) has been made for many years. However, diabetes mellitus still affects many people and contributes significantly to the decline in life expectancy worldwide [1,2]. 8.5% of individuals aged 18 and up had diabetes in 2014. ...
Diabetes mellitus (DM) is by far the most common metabolic disease impacting human health, and Type II diabetes (T2DM) accounts for almost all occurrences of diabetes. This work examined the anti-diabetic efficacy of Brachystegia eurycoma compounds against druggable proteins associated with T2DM and its complications. Fourteen proteins were identified in the literature as T2DM treatment targets and downloaded from the protein data bank. Preliminary screening of the compounds with the protein targets via molecular docking studies showed that the compounds, notably quercetin, kaempferol, and catechin, had high selectivity for GLUT1, aldose reductase, and GLP-1 receptor. Eleven compounds from the plants were chosen as hits based on their favorable binding energies with the proteins. Following molecular docking studies, binding free energy, DFT calculation, ADMET predictions, and QSAR were used to examine further the drug-likeness, efficacy, toxicity, stability, and inhibitory/agonizing prowess of these compounds. The findings in this study showed that these eleven bioactive compounds, which belong to the group of flavonoids and phenolic acids that formed stable complexes with the three proteins, had moderate/low toxicity, are bio-orally available and non-inhibitors of some/all of the CYP450 isozymes. Using trustworthy correlation coefficients (R2), the predicted QSAR models demonstrated the potency of the compounds to function as inhibitors (pIC50) of aldose reductase and GLUT1 and as agonists (pEC50) of GLP-1R. According to DFT calculation of frontier molecular orbitals (FMOs) and global descriptive parameters, it was shown that Quercitrin is the most chemically inert molecule, whereas chlorogenic acid is the most reactive compound. This experimental approach may be utilized to develop drugs that can modulate proteins associated with T2DM without causing off-target effects, as shown in this research.
... Allelic SNPs (single nucleotide polymorphisms) are found in precise numbers throughout the AdipoQ gene sequence [53]. 40 gene loci were found to be associated with the development of type 2 diabetes in a comprehensive investigation of the human genome [54]. Adiponectin gene SNPs rs266729, rs822393, rs3774261, and rs1501299 deliberated mainly with type 2 diabetes in a Kinh Vietnamese population. ...
... AdipoQ rs266729 is a potential SNP for type 2 diabetes susceptibility [53]. Decreased High molecular adiponectin, against a baseline of obesity and AdipoQ genetic variations, changed the metabolic profile, increasing the risk for type 2 diabetes [54]. ...
... Therefore, ADIPOQ can play a causal role in the association of obesity and insulin resistance. Previous studies have identified several SNPs in the ADIPOQ gene, which appears to alter the transcription or activity of the gene [45,46]. ...
Background
Obesity is a complex genetic-based pediatric disorder which triggers life-threatening conditions. Therefore, the understanding the molecular mechanisms of obesity has been a significant approach in medicine. Computational methods allow rapid and comprehensive pathway analysis, which is important for generation of diagnosis and treatment of obesity.Methods and resultsAims of our study are to comprehensively investigate genetic characteristics of obesity in children with non-syndromic, early-onset (< 7 years), and severe obesity (BMI-SDS > 3) through computational approaches. First, the mutational analyses of 41 of obesity-related genes in 126 children with non-syndromic early-onset severe obesity and 76 healthy non-obese controls were performed using the next generation sequencing (NGS) technique, and the NGS data analyzed by using bioinformatics methods. Then, the relationship between pathogenic variants and anthropometric/biochemical parameters was further evaluated. Obtained results demonstrated that the 15 genes (ADIPOQ, ADRB2, ADRB3, IRS1, LEPR, NPY, POMC, PPARG, PPARGC1A, PPARGC1B, PTPN1, SLC22A1, SLC2A4, SREBF1 and UCP1) which directly related to obesity found linked together via biological pathways and/or functions. Among these genes, IRS1, PPARGC1A, and SLC2A4 stand out as the most central ones. Furthermore, 12 of non-synonymous pathogenic variants, including six novels, were detected on ADIPOQ (G90S and D242G), ADRB2 (V87M), PPARGC1A (E680G, A477T, and R656H), UCP1 (Q44R), and IRS1 (R302Q, R301H, R301C, H250P, and H250N) genes.Conclusion
We propose that 12 of non-synonymous pathogenic variations detected on ADIPOQ, ADRB2, PPARGC1A, UCP1, and IRS1 genes might have a cumulative effect on the development and progression of obesity.
... 21,22 Therefore, this study examined the potential associations of four single-nucleotide polymorphisms (SNPs) located in the ADIPOQ gene (rs266729, rs1501299, rs3774261, and rs822393) with T2DM and MetS in a Kinh Vietnamese population. While ADIPOQ SNPs have been reported to be associated with MetS and T2DM in South Asian, East Asian, and Caucasian populations, [23][24][25] this is the first study to investigate this association within the context of a Kinh Vietnamese population. The ADIPOQ SNPs in this study were chosen on the basis that previous studies have shown varying associations with T2DM and MetS, particularly among ethnically different populations. ...
Purpose: Genetic factors play an important role in the development of type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS). However, few genetic association studies related to these disorders have been performed with Vietnamese subjects. In this study, the potential associations of ADIPOQ single nucleotide polymorphisms (SNPs) with T2DM and MetS in a Kinh Vietnamese population were investigated.
Patients and Methods: A study with 768 subjects was conducted to examine the associations of four ADIPOQ SNPs (rs266729, rs1501299, rs3774261, and rs822393) primarily with T2DM and secondarily with MetS. The TaqMan SNP genotyping assay was used to determine genotypes from subjects' DNA samples.
Results: After statistical adjustment for age, sex, and body mass index, the ADIPOQ SNP rs266729 was found to be associated with increased risk of T2DM under multiple inheritance models: codominant (OR = 2.30, 95% CI = 1.16-4.58), recessive (OR = 2.17, 95% CI = 1.11-4.26), and log-additive (OR = 1.32, 95% CI = 1.02-1.70). However, rs1501299, rs3774261, and rs822393 were not associated with risk for T2DM. Additionally, rs266729, rs3774261, and rs822393 were statistically associated with MetS, while rs1501299 was not. Haplotype analysis showed a strong linkage disequilibrium between the SNP pairs rs266729/rs822393 and rs1501299/rs3774261, and the haplotype rs266729(G)/rs822393(T) was not statistically associated with MetS.
Conclusion: The results show that rs266729 is a lead candidate SNP associated with increased risk of developing T2DM and MetS in a Kinh Vietnamese population, while rs3774261 is associated with MetS only. Further functional characterization is needed to uncover the mechanism underlying the potential genotype-phenotype associations.
