Evaluation of single-nucleotide polymorphisms of transcription factor 7-like 2 and ATP2B1 genes as cardiovascular risk predictors in chronic kidney disease

Abstract

Introduction:Cardiovascular disease (CVD) is the primary cause of morbidity and premature mortality in chronic kidney disease (CKD). The transcription factor 7-like 2 (TCF7L2) gene product TCF4 is a transcription factor that acts as a downstream effector in the canonical Wnt signaling pathway and may be important in the development of both type 2 diabetes and renal development and disease. It is, therefore, plausible that mutations in this gene could manifest themselves in reduced kidney function or kidney disease through their effects on hyperglycemia as well as independent of this mechanism. The ATP2B1 gene encodes the plasma membrane calcium ATPase isoform 1, which removes bivalent calcium ions from eukaryotic cells against very large concentration gradients and is responsible for controlling the contraction and dilation of vascular smooth muscles.Aim and Objectives:The aims of this study are (1) to evaluate single-nucleotide polymorphisms (SNPs) of TCF7L2 gene as cardiovascular risk predictors in CKD and (2) to evaluate SNPs of ATP2B1 gene as cardiovascular risk predictors in CKD.Subjects and Methods:Fifty clinically diagnosed CKD patients in the age group between 20 and 60 years of both genders were selected as cases and fifty healthy participants from the master health checkup department were selected as controls. Genomic DNA was extracted based on the spin column kit method. The DNA samples were stored at −20°C until analysis. Genotyping for TCF7L2 gene rs7903146 (C/T) and ATP2B1 gene rs11105354 (A/G) was carried out through polymerase chain reaction.Results:T allele frequency was observed in 12 controls and 23 cases (odds ratio [OR] = 2.2, 95% confidence interval [CI]: 1.0–4.7). CC genotype was observed in 38 controls and 27 cases and CT genotype in 22 cases and 12 controls. A allele was found in 38 cases and 23 controls (OR = 2, 95% CI: 1.1–3.8). The mean values of cholesterol, low-density lipoprotein, triglycerides, glucose, insulin, urea, and creatinine were high in cases when compared to controls.Conclusion:T allele of TCF7L2 gene rs7903146 (C/T) and A allele of ATP2B1 (A/G) gene rs11105354 (A/G) are associated with CVD in CKD patients.

Role of Transcription Factor 7 like 2 and Silent Information Regulator 1 Genes in the Development of Cardiovascular Complications in a Group of Egyptian Patients with Chronic Kidney Disease

“…A previous study performed on a group of ESRD patients with CVD compared to a healthy control group found a significant association between the TCF7L2 gene rs7903146 and risk of CVD occurrence in ESRD patients [20], which supported our results. Another study done on a group of CKD patients compared to a group of healthy controls showed that the T allele of the TCF7L2 gene rs7903146 is a genetic risk factor for CVD in CKD patients [21], which also comes in accordance with our results.…”

“…These findings are supported by a study performed on 2 groups of diabetic patients, one group with DKD and the other group without DKD, which found that patients harboring the TT genotype of rs7903146 were at higher risk to acquire the nephropathy than the CC genotype carriers (p = 0.02), elucidating that the T allele confers genetic risk to develop nephropathy and its complications such as CVD [22], which also come in accordance of our results. A recent study performed on CKD patients with CVD compared to healthy controls reported that the T allele of rs7903146 had a significant association with CVD development in CKD patients (OR = 2.2 and p < 0.05) [21]. Another study performed on ESRD with CVD compared to a group of healthy controls found that CKD patients carrying the T allele of rs7903146 in the TCF7L2 gene were 1.57 times more susceptible for developing CVD than C allele carriers (OR = 1.57 and 95 % CI = 1.31-1.90), which comes in harmony with the results of our study [21].…”

“…A recent study performed on CKD patients with CVD compared to healthy controls reported that the T allele of rs7903146 had a significant association with CVD development in CKD patients (OR = 2.2 and p < 0.05) [21]. Another study performed on ESRD with CVD compared to a group of healthy controls found that CKD patients carrying the T allele of rs7903146 in the TCF7L2 gene were 1.57 times more susceptible for developing CVD than C allele carriers (OR = 1.57 and 95 % CI = 1.31-1.90), which comes in harmony with the results of our study [21].…”

“…As hypertriglyceridemia is one of the traditional risk factors for CVD development in CKD patients; Kulkarni et al, 2019 found that serum triglycerides levels were significantly increased in CKD patients with CVD as compared to normal controls, which is matched with our results as we elucidated a significant positive correlation between serum triglycerides levels and the TT genotype of TCF7L2 gene (p = 0.030), confirming that the T allele of rs7903146 in the TCF7L2 gene confers high risk for CVD development in CKD patients [21].…”

Replacing Saturated Fat with Polyunsaturated Fat Modulates Peripheral Blood Mononuclear Cell Gene Expression and Pathways Related to Cardiovascular Disease Risk Using a Whole Transcriptome Approach

“…[ 28 ] Genome wide association studies and ATP2B1 knockout mouse studies have shown that ATP2B1 may play an important role in the regulation of blood pressure and hypertension through alterations of calcium handling and vasoconstriction in VSMCs. [ 29,30 ] ATP2B1 genomic regions have also been associated with hyperlipidemia and diabetes, [ 31 ] and in a recent study, ATP2B1 gene silencing increased insulin sensitivity in endothelial cells. [ 32 ] Furthermore, in a candidate gene association study, ATP2B1 was associated with coronary artery calcification in chronic kidney disease and myocardial infarction in the general population.…”