- Genetics
- 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
-
-
6,517
View
-
161
Download
-
10
Web of Science
-
9
Crossref
-
Abstract
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 - Shared genetic etiology of vessel diseases: A genome-wide multi-traits association analysis
Jiangwei Song, Ning Gao, Zhe Chen, Guocong Xu, Minjian Kong, Dongdong Wei, Qi Sun, Aiqiang Dong Thrombosis Research.2024; 241: 109102. CrossRef - Association between KCNJ11 rs5219 polymorphisms and gestational diabetes mellitus: A meta-analysis
Jethendra Kumar Muruganantham, Iyshwarya B K, Ramakrishnan Veerabathiran International Journal of Diabetes in Developing Countries.2024;[Epub] 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 - Association between carotid atherosclerosis and presence of intracranial atherosclerosis using three-dimensional high-resolution vessel wall magnetic resonance imaging in asymptomatic patients with type 2 diabetes
Ji Eun Jun, You-Cheol Hwang, Kyu Jeong Ahn, Ho Yeon Chung, Geon-Ho Jahng, Soonchan Park, In-Kyung Jeong, Chang-Woo Ryu 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
Yu-Ting Hsiao, Feng-Chih Shen, Shao-Wen Weng, Pei-Wen Wang, Yung-Jen Chen, Jong-Jer Lee Journal of Personalized Medicine.2021; 11(8): 689. CrossRef - Oxidative Stress Genes in Diabetes Mellitus Type 2: Association with Diabetic Kidney Disease
Athanasios Roumeliotis, Stefanos Roumeliotis, Fotis Tsetsos, Marianthi Georgitsi, Panagiotis I. Georgianos, Aikaterini Stamou, Anna Vasilakou, Kalliopi Kotsa, Xanthippi Tsekmekidou, Peristera Paschou, Stylianos Panagoutsos, Vassilios Liakopoulos, Elena Az Oxidative Medicine and Cellular Longevity.2021;[Epub] CrossRef - Analysis of the association of polymorphisms of genes markers functions of endothelium and vascular-plate hemostasis with development of diabetic foot syndrome
N. I. Troitskaya, K. G. Shapovalov, V. A. Mudrov Acta Biomedica Scientifica.2021; 6(4): 18. CrossRef
|