Common genetic variants in dyslipidemia, inflammation, and angiogenesis pathways associated with diabetic nephropathy in Tunisians

Role of ADIPOQ Gene Variants in the Susceptibility to Diabetic Retinopathy in North-West Indian Population

Diabetic retinopathy (DR) is the leading cause of vision loss and a major microvascular complication of type 2 diabetes (T2D). Adiponectin, an adipocyte-derived protein with anti-inflammatory and insulin-sensitizing effects is reduced in T2D and related metabolic disorders. The ADIPOQ gene has been implicated in T2D susceptibility, but its role in DR remains insufficiently understood. This study investigated the association of three ADIPOQ polymorphisms (rs266729, rs17300539 and rs17846866) with DR in a North-West Indian population. We analyzed 207 DR patients and 274 age- and gender-matched controls (>50 years). Genotyping was performed using PCR– restriction digestion (rs266729, rs17300539) and ARMS-PCR (rs17846866). Allele/genotype distributions were compared by chi-square test. Haplotypes were inferred using Haploview and gene– gene interactions were evaluated by multifactor dimensionality reduction (MDR). All three SNPs conformed to Hardy–Weinberg equilibrium in controls (p>0.05). The minor allele frequencies of rs17300539 and rs17846866 were significantly higher in DR cases than controls (both p<0.001). Under a dominant model, rs266729 (p=0.012, OR=1.66, 95% CI 1.12–2.48), rs17300539 (p<0.001, OR=4.59, 95% CI 2.17–9.71) and rs17846866 (p=0.001, OR=2.30, 95% CI 1.38–3.80) were associated with increased DR risk. Haplotype analysis revealed a protective effect of the G-C-T haplotype (p<0.001, OR=0.52, 95% CI 0.39–0.66). MDR analysis further supported significant SNP–SNP interactions (p=0.001). Our findings demonstrate a strong association of three ADIPOQ variants with DR in the North West Indian population. These variants may contribute to genetic susceptibility and could serve as potential biomarkers for early identification of highrisk individuals.

Association of PCSK9 and CCL22 gene polymorphisms with myocardial infarction in a South Indian population

Association of TCF7/L2 SNPs rs1790314 and rs12255372 Polymorphisms in Type 2 Diabetes Mellitus with Renal and Inflammatory Markers

Background: Type 2 diabetes mellitus (T2DM) is a persistent metabolic disorder characterised by elevated blood glucose levels and influenced by both genetic and environmental factors. Aim: This study investigated the association of TCF7L2 SNPs rs1790314 and rs12255372 with renal and inflammatory markers in type 2 diabetes mellitus. Methods: This cross-sectional study examined biochemical markers and the TCF7L2 SNPs rs12255372 and rs1790314 in 140 patients with T2DM attending the diabetic clinics of Rivers State University Teaching Hospital (RSUTH) and the University of Port Harcourt Teaching Hospital (UPTH), together with 40 non-diabetic controls. Biochemical parameters, including fasting blood glucose (FBG), HbA1c, C-peptide, insulin, HOMA-IR, cystatin C, estimated glomerular filtration rate (eGFR), creatinine, urea, and electrolytes, were measured using colourimetric and ELISA methods. The TCF7L2 variants were genotyped using BigDye Terminator sequencing. Data on these parameters and the TCF7L2 genotypes were analysed using GraphPad Prism, SPSS, and Excel. Descriptive statistics were presented as means ± SD, while inferential analyses included Student's t-test, Pearson's correlation, linear regression, and one-way ANOVA. Statistical significance was set at p < 0.05. Results: The study found an increasing prevalence of T2DM in Port Harcourt in recent years, with rates of 23% in males and 21% in females, and a glycaemic control rate of 38.75%. The TCF7L2 genotype distribution showed that 32.5% had the CC genotype and 11.25% had the CT/TT genotypes at rs1790314, whereas 41.25% had the GG genotype and 3.75% had the GT/TT genotypes at rs12255372. Abnormalities such as hyponatraemia, low chloride levels, and hyperkalaemia were observed in patients with poorly controlled T2DM. Physical activity was associated with better cardiovascular health, as indicated by lower cardiac troponin I (cTnI) levels. Standard antidiabetic drugs, including metformin (Glucophage) and sulfonylureas (Amaryl), were associated with dyslipidaemia, particularly in males, characterised by reduced HDL-C and triglyceride levels and increased atherogenic ratios such as TC/TG. An association was also found between chloride levels and the T allele at rs1790314. BMI and WHR did not correlate with the CT/TT polymorphisms at rs1790314 or the GT/TT polymorphisms at rs12255372, although both were higher in individuals with T2DM carrying the TCF7L2 variants. The rs1790314 CT/TT mutation was associated with higher triglyceride, TC/TG, and TC/HDL ratios and lower HDL-C levels. Insulin resistance, indicated by increased C-peptide levels, was observed in rs1790314 CT/TT carriers, while renal abnormalities associated with rs12255372 GT/TT correlated with cystatin C. Overall, TCF7L2 variants were associated with dyslipidaemia, elevated cystatin C, and increased C-peptide levels. Patients with mutant T alleles in both variants had significantly higher HbA1c, WHR, BMI, lipid, atherogenic marker, and troponin I levels. Conclusion: The findings suggest that increased insulin resistance and impaired cellular uptake occurred alongside significantly higher C-peptide levels in individuals with the CT/TT polymorphic variants of transcription factor 7-like 2 (TCF7L2) rs1790314. Furthermore, renal abnormalities were associated with the TCF7L2 rs12255372 GT/TT polymorphic variant, which was positively associated with cystatin C in participants with type 2 diabetes mellitus (T2DM) who expressed TCF7L2.

Integrative Clinical and Functional Characterization of the TCF7L2 rs7903146 Variant Reveals Regulatory Mechanisms Linking Genetic Susceptibility to Oxidative Stress in Type 2 Diabetes

Predictive evidence was provided suggesting that rs7903146 may have tissue-specific regulatory relevance and may be indirectly linked to metabolic and WNT/β-catenin signaling pathways, and the proposed regulatory mechanisms require experimental validation.

Association of Insulin Receptor Substrate 1 Gene Polymorphism (Rs2943640) with Glibenclamide Therapeutic Response in Iraqi Patients with Type 2 Diabetes Mellitus

Objective: This study aims to evaluate the association of the insulin receptor substrate 1 (IRS1) rs2943640 single nucleotide polymorphism (SNP) with the effectiveness of glibenclamide therapy in Iraqi diabetic patients treated with glibenclamide. Methods: This cross-sectional study was conducted in Karbala City, located in central Iraq, from September 2024 to December 2025, and enrolled a total of 160 individuals with a confirmed diagnosis of type 2 diabetes mellitus (T2DM). Venous blood samples were obtained from all participants for the genotyping of the rs2943640 (A/C) SNP and assessment of biochemical parameters, including glycemic indices, lipid profiles, and liver and kidney functions. Results: The genotype frequencies of rs2943640 A/C are 30 % for AA, 61.9 % for AC, and 8.1 % for CC. No statistically significant differences between the three patient groups in biochemical parameters, including glycemic indices, lipid profiles, kidney functions, and aspartate aminotransferase (AST), while alanine aminotransferase (ALT) showed a significant difference among the patient groups. Conclusion: Our results show no statistically significant association between IRS1 rs2943640 (A/C) SNP and therapeutic response to glibenclamide in Iraqi T2DM patients.

EDN1 and PHACTR1 variants and the NOS3-PHACTR1 interaction may shape susceptibility and severity in coronary artery disease.

Coronary artery disease (CAD) is a complex disorder influenced by endothelial dysfunction, vascular inflammation, and thrombosis. This study evaluated selected genetic variants in endothelin signaling (EDN1, PHACTR1), nitric oxide metabolism (NOS3), and fibrinolysis (SERPINE1/PAI-1) in relation to CAD susceptibility, major clinical sub-phenotypes, and disease severity in a Turkish study population. A total of 1256 individuals who underwent coronary angiography were enrolled, including 748 CAD patients and 508 non-CAD controls. Genotyping of EDN1 rs3087459, PHACTR1 rs9349379, NOS3 rs1799983, and PAI-1 4G/5G variants were performed using quantitative real-time PCR. Logistic regression, haplotype, and gene-gene interaction analyses were conducted under multiple inheritance models. The EDN1 CC genotype was significantly associated with CAD (OR = 5.759, 95% CI: 1.319-25.149, p = 0.020), severe CAD (p = 0.012), and C allele with myocardial infarction (OR = 1.640, 95% CI: 1.091-2.465, p = 0.017) in males. Moreover, the PHACTR1 GG genotype was associated with premature CAD (OR = 1.721, 95%CI: 1.076-2.753, p = 0.024), and greater angiographic severity (p < 0.05). The NOS3 T allele carrier males had an increased risk for diabetes (OR = 1.449, 95%CI:1.057-1.985 p = 0.021), and CAD complexed with diabetes (CAD-DM) (OR = 1.619, 95%CI:1.004-2.610, p = 0.048). Notably, the interaction between NOS3 and PHACTR1 variants was consistently associated with CAD, severe CAD, premature CAD, and CAD-DM, and was further supported by higher stenosis severity indices and elevated troponin levels (p < 0.05). These findings demonstrate that variation within endothelial pathways extends beyond CAD susceptibility to shape angiographic complexity and clinical severity. Notably, a synergistic interaction between PHACTR1 and NOS3 modulates CAD related phenotypes, emphasizing that coordinated pathway disturbances contribute to CAD heterogeneity more than isolated variants.