Genetic polymorphism in ADRB-1 is associated with type 2 diabetes susceptibility in Iranian population

Galavi, Hamidreza; Noorzehi, Nafiseh; Saravani, Ramin; Sargazi, Saman; Mollashahee-Kohkan, Fatemeh; Shahraki, Hojat

doi:10.1016/j.genrep.2018.06.019

Cited by 15 publications

(5 citation statements)

References 33 publications

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“…Polymorphisms in the three subtypes of β-adrenoceptor (ADRB1, ADRB2, and ADRB3 genes) show a correlation with obesity and body weight-related disorders [66]. ADRB1 also contributes to increased secretion of renin and ghrelin hormones, which are associated with T2D and insulin resistance [67]. Studies suggest that p.Arg389Gly polymorphism in the ADRB1 may be a potential genetic biomarker to assess the risk of developing cardiovascular diseases [68].…”

Section: Discussionmentioning

confidence: 99%

Involvement of Essential Signaling Cascades and Analysis of Gene Networks in Diabesity

Rajan

et al. 2020

Genes

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(1) Aims: Diabesity, defined as diabetes occurring in the context of obesity, is a serious health problem that is associated with an increased risk of premature heart attack, stroke, and death. To date, a key challenge has been to understand the molecular pathways that play significant roles in diabesity. In this study, we aimed to investigate the genetic links between diabetes and obesity in diabetic individuals and highlight the role(s) of shared genes in individuals with diabesity. (2) Methods: The interactions between the genes were analyzed using the Search Tool for the Retrieval of Interacting Genes (STRING) tool after the compilation of obesity genes associated with type 1 diabetes (T1D), type 2 diabetes (T2D), and maturity-onset diabetes of the young (MODY). Cytoscape plugins were utilized for enrichment analysis. (3) Results: We identified 546 obesity genes that are associated with T1D, T2D, and MODY. The network backbone of the identified genes comprised 514 nodes and 4126 edges with an estimated clustering coefficient of 0.242. The Molecular Complex Detection (MCODE) generated three clusters with a score of 33.61, 16.788, and 6.783, each. The highest-scoring nodes of the clusters were AGT, FGB, and LDLR genes. The genes from cluster 1 were enriched in FOXO-mediated transcription of oxidative stress, renin secretion, and regulation of lipolysis in adipocytes. The cluster 2 genes enriched in Src homology 2 domain-containing (SHC)-related events triggered by IGF1R, regulation of lipolysis in adipocytes, and GRB2: SOS produce a link to mitogen-activated protein kinase (MAPK) signaling for integrins. The cluster 3 genes ere enriched in IGF1R signaling cascade and insulin signaling pathway. (4) Conclusion: This study presents a platform to discover potential targets for diabesity treatment and helps in understanding the molecular mechanism.

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Section: Discussionmentioning

confidence: 99%

Involvement of Essential Signaling Cascades and Analysis of Gene Networks in Diabesity

Rajan

et al. 2020

Genes

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“…As disease susceptibility can't be attributed to a single polymorphism or allele, but rather to a combination of multiple polymorphisms [41][42][43][44]. We evaluated gene-gene interactions using multifactor dimension reduction (MDR), a novel method to examine the combined effects of multiple factors in disease susceptibility [45].…”

Section: Plos Onementioning

confidence: 99%

The associations of IGF2, IGF2R and IGF2BP2 gene polymorphisms with gestational diabetes mellitus: A case-control study

Li,

She,

Zhang

et al. 2024

PLoS ONE

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Objective To investigate the associations of Insulin-like growth factor-II (IGF2) gene, Insulin-like growth factor-II receptor (IGF2R) gene and Insulin-like growth factor-II binding protein 2 (IGF2BP2) gene polymorphisms with the susceptibility to gestational diabetes mellitus (GDM) in Chinese population. Methods A total of 1703 pregnant women (835 GDM and 868 Non-GDM) were recruited in this case-control study. All participants underwent prenatal 75 g oral glucose tolerance test (OGTT) examinations during 24–28 gestational weeks at the Maternal and Child Health Hospital of Hubei Province from January 15, 2018 to March 31, 2019. Genotyping of candidate SNPs (IGF2 rs680, IGF2R rs416572, IGF2BP2 rs4402960, rs1470579, rs1374910, rs11705701, rs6777038, rs16860234, rs7651090) was performed on Sequenom MassARRAY platform. Logistic regression analysis was conducted to investigate the associations between candidate SNPs and risk of GDM. In addition, multifactor dimensionality reduction (MDR) method was applied to explore the effects of gene-gene interactions on GDM risk. Results There were significant distribution differences between GDM group and non-GDM group in age, pre-pregnancy BMI, education level and family history of diabetes (P < 0.05). After adjusted for age, pre-pregnancy BMI, education level and family history of diabetes, there were no significant associations of the candidate SNPs polymorphisms and GDM risk (P > 0.05). Furthermore, there were no gene-gene interactions on the GDM risk among the candidate SNPs (P > 0.05). However, the fasting blood glucose (FBG) levels of rs6777038 CT carriers were significantly lower than TT carriers (4.69±0.69 vs. 5.03±1.57 mmol/L, P < 0.01), and the OGTT-2h levels of rs6777038 CC and CT genotype carriers were significantly lower than TT genotype carriers (8.10±1.91 and 8.08±1.87 vs. 8.99±2.90 mmol/L, P < 0.01). Conclusions IGF2 rs680, IGF2R rs416572, IGF2BP2 rs4402960, rs1470579, rs11705701, rs6777038, rs16860234, rs7651090 polymorphisms were not significantly associated with GDM risk in Wuhan, China. Further lager multicenter researches are needed to confirm these results.

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“… 15 Other gene polymorphisms have also been recognized as predisposing risk factors and therapeutic targets for DM with or without kidney diseases. These include sirtuin 1 ( SIRT1 ) rs12778366 and rs3758391, 16 β1‐Adrenegic receptor ( ADRB‐1 ) rs1801253C/G, 17 NR1H2 gene encoding LXRβ (28,514,894 and rs2303044), 18 miR143/145 cluster, 19 and miR29a (rs157907A/G). 20 …”

Section: Introductionmentioning

confidence: 99%

Association of a single nucleotide polymorphism in SOD2 with susceptibility for the development of diabetic nephropathy in patients with type 2 diabetes: A Saudi population study

Sultan,

Alharbi,

Alrayes

et al. 2023

Endocrino Diabet & Metabol

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IntroductionOne of the complications of diabetes mellitus (DM) is diabetic nephropathy (DN), which plays a significant role in the progression of end‐stage renal disease. Oxidative stress is implicated in DN pathogenesis, and genetic variations in antioxidant enzymes such as superoxide dismutase 2 (SOD2) and catalase (CAT) may contribute to the susceptibility. This study aimed to investigate the potential association between single nucleotide polymorphisms (SNPs) in antioxidant enzymes, specifically SOD2 rs4880 and CAT rs769217, and the risk of T2D and susceptibility to DN within the Saudi population.MethodsThis case–control study included 150 participants, comprising 50 patients with T2D without DN (group 1), 50 patients with T2D with DN (group 2), and 50 healthy participants (group 3). The samples were genotyped using real‐time PCR for SOD2 rs4880 and CAT rs769217 SNPs. Sanger sequencing was used for validation. Statistical analyses were performed to explore associations between these SNPs and T2D with or without DN.ResultsNo significant difference was observed in CAT rs769217 expression between the groups. However, a significant difference was observed in SOD2 rs4880 expression between the healthy controls and patients with T2D with DN (p = .028). Furthermore, SOD2 rs4880 was associated with approximately threefold increased risk of DN in patients with T2D compared to that in healthy participants (odds ratio [OR] = 2.99 [1.31–6.83]). Validation through Sanger sequencing further confirmed these findings.ConclusionsThe findings of this study provide evidence that SOD2 rs4880 SNP may contribute to inadequate defence by the antioxidant enzyme, SOD2, against DM‐induced oxidative stress and thus cause DN in Saudi patients with T2D. Therefore, SOD2 rs4880 may serve as a predictive marker to prevent the development and progression of DN in patients with T2D.

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Genetic polymorphism in ADRB-1 is associated with type 2 diabetes susceptibility in Iranian population

Cited by 15 publications

References 33 publications

Involvement of Essential Signaling Cascades and Analysis of Gene Networks in Diabesity

Involvement of Essential Signaling Cascades and Analysis of Gene Networks in Diabesity

The associations of IGF2, IGF2R and IGF2BP2 gene polymorphisms with gestational diabetes mellitus: A case-control study

Association of a single nucleotide polymorphism in SOD2 with susceptibility for the development of diabetic nephropathy in patients with type 2 diabetes: A Saudi population study

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