Analysis of FOXO4 Gene Polymorphism in Cardiac Patients from Faisalabad, Pakistan

Abstract

Background: Cardiovascular disease (CVD) involves complex interactions between genetic susceptibility and metabolic risk factors. Forkhead box O4 (FOXO4) regulates oxidative stress, inflammation, and cellular survival. This study investigated two FOXO4 polymorphisms and their associations with CVD and selected biochemical parameters in adults from Faisalabad, Pakistan.

Methods: This case–control study included 100 patients with clinically diagnosed CVD and 50 apparently healthy controls aged over 30 years. Venous blood samples were collected for molecular and biochemical investigations. Genotyping targeted rs1404536455 (G/A) and rs1222386114 (T/C). Biochemical assessments included serum lipid profiles, alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea, creatinine, and uric acid. Genotype distributions were compared using an exact test, and biochemical comparisons were evaluated using one-way analysis of variance.

Results: For rs1404536455, the AA genotype occurred in 24.0% of patients and 8.5% of genotyped controls, with a significant difference in overall genotype distribution (p = 0.010). No significant genotype-distribution difference was observed for rs1222386114 (p = 0.409). Unadjusted biochemical comparisons identified differences across rs1404536455 genotypes in ALT (p = 0.019) and creatinine (p = 0.048), and across rs1222386114 genotypes in LDL cholesterol (p = 0.007), ALT (p = 0.004), and uric acid (p = 0.006). Other biochemical comparisons were not statistically significant.

Conclusion: FOXO4 rs1404536455 demonstrated differences in genotype distribution between cardiovascular patients and healthy controls, while selected biochemical parameters varied across genotype groups. These findings provide population-specific insights into the potential contribution of FOXO4 genetic variability to cardiovascular disease.