The TCF7L2 rs12255372 polymorphism, particularly the T allele, is associated with an increased risk of type 2 diabetes mellitus and early renal dysfunction, and may serve as a promising molecular marker for early risk stratification of diabetic kidney disease.
Abstract
Background. Polymorphisms of the TCF7L2 gene are among the most important genetic risk factors for type 2 diabetes mellitus (T2DM); however, their role in the development of diabetic kidney disease (DKD) remains insufficiently understood.Objective. To evaluate the association between the TCF7L2 rs12255372 polymorphism and the risk of type 2 diabetes mellitus, as well as its relationship with renal function.Materials and Methods. The study included 86 patients with T2DM and 24 healthy controls. Genotyping of the TCF7L2 rs12255372 polymorphism was performed using polymerase chain reaction. Allele and genotype distributions were analyzed together with renal function parameters, including estimated glomerular filtration rate (eGFR), urea, creatinine, nephrin, and cystatin C.Results. The T allele was significantly more frequent in patients than in controls (29.7% vs. 2.1%; OR=19.8; 95% CI: 4.54–86.37; p=0.01). Carriers of the TT genotype demonstrated a significantly lower eGFR (74.8±3.24 mL/min/1.73 m²; p<0.01) and higher serum urea levels (7.90±1.28 mmol/L; p<0.05) compared with carriers of the GG and GT genotypes. Although differences in nephrin and cystatin C levels were not statistically significant, an increasing trend was observed among TT carriers.Conclusions. The TCF7L2 rs12255372 polymorphism, particularly the T allele, is associated with an increased risk of type 2 diabetes mellitus and early renal dysfunction. This genetic variant may serve as a promising molecular marker for early risk stratification of diabetic kidney disease.
OLR1 rs11053646 SNP does not appear to be associated with T2D risk in Saudi adults, and small sample size may have limited statistical power to detect potential associations.
V. Vennu· Endocrine, Metabolic & Immun...· 0 citations
Background ATP-sensitive potassium channels regulate insulin release, with the KCNJ11 gene encoding the Kir6.2 channel’s pore subunit. The E23K variant, previously linked to type 2 diabetes (T2DM), was examined in a large Lebanese cohort to determine its relationship to diabetic retinopathy (DR) severity and glycemic control. Methods A case–control sample of 1,415 adults with T2DM were classified as diabetes without retinopathy (DWR; n = 933), non-proliferative DR (NPDR; n = 342), or proliferative DR (PDR; n = 140) based on ETDRS criteria, and compared with 1,389 normoglycemic controls. Logistic regression was used to assess genetic associations across multiple inheritance models. Sensitivity analyses stratified by diabetes duration and area under the ROC curve (AUC) compared discrimination using age and sex, with or without genotype. Results The K allele was more frequent in T2DM than in controls. Although E23K was not associated with overall DR, its effect was stage-specific. In comparisons of PDR with DWR, each additional K allele increased PDR odds, and K/K homozygosity showed a stronger recessive effect. The K/K genotype was notably enriched among DR patients with HbA1c ≤ 7.0%, indicating an elevated risk under good glycemic control, but showed no signal in those with poorer control. It was also overrepresented in PDR. Risk associations were more pronounced in individuals with diabetes duration ≥10 years, and adding genotype information resulted in a small increase in model discrimination beyond age and sex alone (AUC = 0.552–0.598; ΔAUC = 0.046). However, the overall discriminatory performance remained poor, suggesting limited clinical utility of E23K genotyping as an isolated predictive marker. Conclusion In this Middle Eastern population, KCNJ11 E23K showed a stage-specific association with prevalent proliferative, vision-threatening DR rather than with earlier stages of retinopathy. This supports the potential utility of E23K as a marker of advanced retinopathy severity, although longitudinal studies in diverse ethnic groups are required to determine its relationship with disease progression.
Rita Nemr, A. Echtay, P. Kanabekova et al.· Frontiers in Medicine· 0 citations
Background: Psoriasis is an inflammatory skin disease caused by genetic and environmental factors. Although data on Iraqi patients are poor, there may be a relation between the vitamin D receptor (VDR) gene and susceptibility to psoriasis. Objective: This study aims to analyze the association between the VDR ApaI (rs7975232) gene polymorphism and the tendency toward psoriasis in Iraqi patients and to evaluate serum levels of vitamin D3, ferritin, and zinc. Method: A case-control study was conducted on 45 patients with psoriasis and 35 age- and sex-matched control group. Genotyping of the Vitamin D receptor rs7975232 polymorphism was done by high-resolution melting (HRM) analysis. Automated analyzers tested serum vitamin D3, ferritin, and zinc levels. Statistical analyses were performed using GraphPad Prism software. Results: The allele frequency was considerably higher in patients (40.0%) than in the control group (24.3%), which conferred an elevated risk of psoriasis (OR = 2.07, 95% CI: 1.01–4.24, p = 0.046). AA carriers showed the lowest mean vitamin D3 level (15.0 ± 3.7 ng/mL, p = 0.0043) and highest mean ferritin level (223.6 ± 67.2 ng/mL, p = 0.0136). Levels of vitamin D3 and zinc were considerably lower in patients than in the control group (p<0.001 for both), and the highest mean ferritin level (p<0.001). Conclusions: The A allele of the VDR rs7975232 polymorphism was associated with increased susceptibility to psoriasis in Iraqi patients. AA carriers showed the lowest mean vitamin D3 and zinc levels and the highest mean ferritin level; however, genotype-related differences in these biochemical parameters were not statistically significant within the patient group.
Safana S. Dardouh, M. Mohammed, Mohammad M. F. Al-Halbosiy· Adolescência e Saúde· 0 citations
Multivariable analysis provides evidence supporting an independent association between the MIA3 rs17465637 variant and CAD susceptibility in this Saudi cohort, and the observed associations with adverse lipid profiles further provide evidence linking this specific locus to the molecular mechanisms underlying cardiovascular disease.
N. Bogari, Samar N. Ekram, Amr A. Amin et al.· Diagnostics· 0 citations