TCF7L2 polymorphism a prominent marker among subjects with Type-2-Diabetes with a positive family history of diabetes

Juttada, Udyama; Kumpatla, Satyavani; Parveen, Rizwana; Viswanathan, Vijay

doi:10.1016/j.ijbiomac.2020.04.240

Cited by 13 publications

(8 citation statements)

References 26 publications

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“…One of the most prevalent genetic variations that predispose an individual to diabetes and its complications is SNPs [9][10][11][12]. It induces nucleotide substitution at specific locations in a gene, causing variations in susceptibility to disease.…”

Section: Introductionmentioning

confidence: 99%

Genetic Polymorphism of the Nrf2 Promoter Region (rs35652124) Is Associated with the Risk of Diabetic Foot Ulcers

Rajan

Umapathy

Ali

et al. 2020

Oxidative Medicine and Cellular Longevity

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The genetic polymorphism in the nuclear factor erythroid 2-related factor 2 (Nrf2) gene has been reported as one of the prognosis markers for various diseases, including cancer. Nrf2 is a key transcription factor involved in wound healing by regulating angiogenesis. We investigated the genetic association of NRF2 single-nucleotide polymorphism rs35652124 with T2DM and DFU and assessed its functional impact. A total of 400 subjects were recruited for the study and categorized into three groups: infected DFU patients (DFU, n=100), T2DM patients without complications (T2DM, n=150), and healthy adults with normal glucose tolerance (NGT, n=150). The subjects were genotyped by PCR-RFLP, and the polymorphism was identified by bidirectional Sanger sequencing. The expression of NRF2, IL-10, TNF-α, and IL-6 was studied by qPCR to evaluate the functional impact of rs35652124. The “TT” genotype of rs35652124 was associated with a significant risk for T2DM [OR=2.2 (1.2-4.2), p=0.01] and DFU [OR=7.9 (4-14.9), p<0.0001]. A significant decrease in transcriptional levels of NRF2 and IL-10 and a remarkable increase in TNF-α and IL-6 were observed in subjects with TT genotype. In conclusion, rs35652124 (TT) is a harmful genetic variant that predisposes to insulin resistance and impaired angiogenesis. Hence, it may serve as a diagnostic genetic marker for T2DM and DFU in combination with different inflammatory markers.

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Section: Introductionmentioning

confidence: 99%

Genetic Polymorphism of the Nrf2 Promoter Region (rs35652124) Is Associated with the Risk of Diabetic Foot Ulcers

Rajan

Umapathy

Ali

et al. 2020

Oxidative Medicine and Cellular Longevity

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“…By regulating the Wnt signal pathway, it can stimulate insulin secretion, reduce insulin resistance, and play an important role in maintaining blood glucose homeostasis (5,6). The common variations in TCF7L2 gene have been identified as strong predictors of T2DM risk (7)(8)(9)(10). In the North Indian population, the researchers concluded that rs7901695 heterozygosity and mutant genotype were associated with an increased risk of T2DM (11).…”

Section: Introductionmentioning

confidence: 99%

The correlation between transcription factor 7-like 2 gene polymorphisms and susceptibility of gestational diabetes mellitus in the population of central China: A case–control study

Zhang

Deng²,

Li³

et al. 2022

Front. Endocrinol.

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ObjectiveTo investigate the correlation between transcription factor 7-like 2 (TCF7L2) gene polymorphisms and gestational diabetes mellitus (GDM) risk in the central Chinese population.MethodsThis case–control study examined the association of seven TCF7L2 gene single-nucleotide polymorphisms (SNPs) (rs11196218, rs4506565, rs7895340, rs7901695, rs11196205, rs12243326, and rs290487) with GDM risk in the central Chinese population (843 GDM and 877 controls). The clinical information and blood samples were collected by trained interviewers and nurses. Genotyping of SNPs was conducted on the Sequenom MassARRAY platform. Statistical analyses including t-test, ANOVA, chi-square test, Fisher’s exact test, and logistic regression were performed.ResultsDifferences in age, pre-pregnant body mass index (BMI), and family history of type 2 diabetes mellitus (T2DM) between the case and control groups were significant (p < 0.05). Compared with the wild-type genotype, pregnant women with genotypes of rs4506565-AT (OR = 1.89, 95%CI: 1.18–3.02), rs7895340 GA (OR = 1.93, 95%CI: 1.06–3.54), rs7901695-TC (OR = 1.79, 95%CI: 1.11–2.88), and rs11196205-GC (OR = 2.15, 95%CI: 1.16–3.98) had a significantly higher risk of GDM, adjusted by age, pre-pregnant BMI, and family history of T2DM. Functional annotation showed that all these four SNPs fell in the functional elements of human pancreatic islets. Further cumulative effects analysis concluded that when participants carried all these four risk genotypes, the risk of GDM was 3.51 times (OR = 3.51, 95%CI: 1.38–8.90) than that of those without any risk genotypes.ConclusionsThe findings of this study suggested that rs4506565, rs7895340, rs7901695, and rs11196205 were the genetic susceptibility SNPs of GDM in the central Chinese population. Further studies are needed to validate our findings and clarify the underlying mechanisms.

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“…Insulin/IGF activates metabolic and mitogenic signaling pathways, hyperglycemia provides energy for the growth of cancer cells, and inflammatory cytokines counter-affect apoptosis of cancer cells (Wang et al, 2020a). It should be noted that in the pathogenesis of cancer, in addition to external factors, there are numerous microRNAs, along with genes that encode proteins involved in the regulation of the expression of genes associated with the disease (Larsson et al, 2007;Miller et al, 2010;González et al, 2017;Mahajan et al, 2018;Juttada et al, 2020;Wang et al, 2020bWang et al, , 2021Dorling et al, 2022;Zhou et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

The initial study of NF-κBIA gene polymorphism in a small group of patients with cancer and diabetes mellitus

2022

IMBB

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Nowadays, the search for various classes of molecular markers, including genetic ones, is relevant for the early and accurate diagnosis of hereditary and non-hereditary diseases. Different types of mutations arising in genes involved in the regulation of several metabolic and signaling pathways play an important role in the development of common diseases such as various forms of cancer and Diabetes Mellitus. One of such mutations is SNP type mutation of A→G (2758 A> G, (rs 696)) occurring in the 3'-UTR region of the gene of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha subunit (NF-κBIA or IκBα). The main objective of this study was to investigate the possible associations of this mutation with cancer and diabetes among patients with cancer only (group C, 24 persons), patients with cancer and diabetes mellitus at the same time (group C+DM, 24 people) and conditionally healthy individuals (group N, 24 persons). The frequency of the allele A in the studied groups (C, C+DM, N) and population (P) was 43.

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TCF7L2 polymorphism a prominent marker among subjects with Type-2-Diabetes with a positive family history of diabetes

Cited by 13 publications

References 26 publications

Genetic Polymorphism of the Nrf2 Promoter Region (rs35652124) Is Associated with the Risk of Diabetic Foot Ulcers

Genetic Polymorphism of the Nrf2 Promoter Region (rs35652124) Is Associated with the Risk of Diabetic Foot Ulcers

The correlation between transcription factor 7-like 2 gene polymorphisms and susceptibility of gestational diabetes mellitus in the population of central China: A case–control study

The initial study of NF-κBIA gene polymorphism in a small group of patients with cancer and diabetes mellitus

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