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Nantarat Komanasin 1 Article
Genetics
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Association of Combined TCF7L2 and KCNQ1 Gene Polymorphisms with Diabetic Micro- and Macrovascular Complications in Type 2 Diabetes Mellitus
Rujikorn Rattanatham, Nongnuch Settasatian, Nantarat Komanasin, Upa Kukongviriyapan, Kittisak Sawanyawisuth, Phongsak Intharaphet, Vichai Senthong, Chatri Settasatian
Diabetes Metab J. 2021;45(4):578-593.   Published online March 22, 2021
DOI: https://doi.org/10.4093/dmj.2020.0101
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  • 7 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Vascular complications are the major morbid consequences of type 2 diabetes mellitus (T2DM). The transcription factor 7-like 2 (TCF7L2), potassium voltage-gated channel subfamily Q member 1 (KCNQ1), and inwardly-rectifying potassium channel, subfamily J, member 11 gene (KCNJ11) are common T2DM susceptibility genes in various populations. However, the associations between polymorphisms in these genes and diabetic complications are controversial. This study aimed to investigate the effects of combined gene-polymorphisms within TCF7L2, KCNQ1, and KCNJ11 on vascular complications in Thai subjects with T2DM.
Methods
We conducted a case-control study comprising 960 T2DM patients and 740 non-diabetes controls. Single nucleotide polymorphisms in TCF7L2, KCNQ1, and KCNJ11 were genotyped and evaluated for their association with diabetic vascular complications.
Results
The gene variants TCF7L2 rs290487-T, KCNQ1 rs2237892-C, and KCNQ1 rs2237897-C were associated with increased risk of T2DM. TCF7L2 rs7903146-C, TCF7L2 rs290487-C, KCNQ1 rs2237892-T, and KCNQ1 rs2237897-T revealed an association with hypertension. The specific combination of risk-alleles that have effects on T2DM and hypertension, TCF7L2 rs7903146-C, KCNQ1 rs2237892-C, and KCNQ1 rs2237897-T, as genetic risk score (GRS), pronounced significant association with coronary artery disease (CAD), cumulative nephropathy and CAD, and cumulative microvascular and macrovascular complications (respective odds ratios [ORs] with 95% confidence interval [95% CI], comparing between GRS 2–3 and GRS 5–6, were 7.31 [2.03 to 26.35], 3.92 [1.75 to 8.76], and 2.33 [1.13 to 4.79]).
Conclusion
This study demonstrated, for the first time, the effect conferred by specific combined genetic variants in TCF7L2 and KCNQ1 on diabetic vascular complications, predominantly with nephropathy and CAD. Such a specific pattern of gene variant combination may implicate in the progression of T2DM and life-threatening vascular complications.

Citations

Citations to this article as recorded by  
  • Genetic Risk Scores Identify People at High Risk of Developing Diabetic Kidney Disease: A Systematic Review
    Aleena Shujaat Ali, Cecilia Pham, Grant Morahan, Elif Ilhan Ekinci
    The Journal of Clinical Endocrinology & Metabolism.2024; 109(5): 1189.     CrossRef
  • Saudi Community-Based Screening Study on Genetic Variants in β-Cell Dysfunction and Its Role in Women with Gestational Diabetes Mellitus
    Amal F. Alshammary, Malak Mohammed Al-Hakeem, Imran Ali Khan
    Genes.2023; 14(4): 924.     CrossRef
  • Association between KCNJ11 E23K polymorphism and the risk of type 2 diabetes mellitus: A global meta-analysis
    Yaxuan Ren, Wenfei Zhu, Jikang Shi, Aiyu Shao, Yi Cheng, Yawen Liu
    Journal of Diabetes and its Complications.2022; 36(5): 108170.     CrossRef
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    Diabetes Research and Clinical Practice.2022; 191: 110067.     CrossRef
  • Multiple Single Nucleotide Polymorphism Testing Improves the Prediction of Diabetic Retinopathy Risk with Type 2 Diabetes Mellitus
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    Journal of Personalized Medicine.2021; 11(8): 689.     CrossRef
  • Oxidative Stress Genes in Diabetes Mellitus Type 2: Association with Diabetic Kidney Disease
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    Oxidative Medicine and Cellular Longevity.2021; 2021: 1.     CrossRef
  • Analysis of the association of polymorphisms of genes markers functions of endothelium and vascular-plate hemostasis with development of diabetic foot syndrome
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    Acta Biomedica Scientifica.2021; 6(4): 18.     CrossRef

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