Key result
High TCF7L2 and KCNQ1 genetic risk score linked to ~631% higher CAD risk in T2D.
Why the study?
Associations between polymorphisms in T2DM susceptibility genes (TCF7L2, KCNQ1, and KCNJ11) and diabetic complications remain controversial.
Does a specific combination of TCF7L2 and KCNQ1 gene polymorphisms increase the risk of vascular complications in Thai subjects with T2DM?
Case-Control (n=1,700)
Does a specific combination of TCF7L2 and KCNQ1 gene polymorphisms increase the risk of vascular complications in Thai subjects with T2DM?
Odds Ratio: 7.31 (95% CI 2.03–26.35)
p-value: p=0.002
A specific combination of genetic variants in TCF7L2 and KCNQ1 is strongly associated with diabetic vascular complications, particularly nephropathy and CAD, in Thai patients with T2DM.
May support genetic screening in Thai T2DM; leaves open prospective validation of risk scores for vascular complications.
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.
No takes yet. Share an insight, caveat, or question.
Rattanatham et al. (2021) conducted a case-control in Type 2 Diabetes Mellitus and vascular complications (n=1,700). Combined TCF7L2 and KCNQ1 gene polymorphisms (Genetic Risk Score) vs. Low genetic risk score was evaluated on Coronary artery disease (CAD) (OR 7.31, 95% CI 2.03-26.35, p=0.002). A high genetic risk score combining TCF7L2 and KCNQ1 risk alleles was significantly associated with an increased risk of coronary artery disease (OR 7.31) and cumulative vascular complications in patients with type 2 diabetes.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: