Methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms are associated with major depressive disorder in the Saudi patients attending Erada complex for mental health and Erada services - Jeddah, Saudi Arabia.

Background: Major Depressive Disorder (MDD) is a prevalent and debilitating mental disorder that has been linked to hyperhomocysteinemia and folate deficiency. These conditions are influenced by the methylenetetrahydrofolate reductase (MTHFR) gene, which plays a crucial role in converting homocysteine to methionine and is essential for folate metabolism and neurotransmitter synthesis, including serotonin. Study aim: This study explored the association between MTHFR C677T and A1298C polymorphisms among Saudi MDD patients attending the Erada Complex for Mental Health and Erada Services outpatient clinic in Jeddah, Saudi Arabia. Methods: The study involved 87 MDD patients and 87 control subjects. Saliva samples were collected, and genomic DNA was extracted. Polymerase chain reaction-restriction fragment length polymorphism was used to detect MTHFR gene polymorphisms. Results: A significant difference was observed in the distribution of genotype frequencies for MTHFR C677T and A1298C polymorphisms between MDD patients and controls in the Saudi cohort (C677T: P = 0.001; A1298C: P = 0.01) Risk analysis indicated that individuals with the mutant TT genotype of the C677T polymorphism (Odd Ratio (OR) = 6.80, CI 95% = 1.47-31.36, P = 0.01) and the mutant CC genotype of the A1298C polymorphism (OR = 2.64, CI 95% = 1.36-5.13, P = 0.004) are more common in MDD patients, suggesting a higher risk for depression. Gender-specific analyses showed that the MTHFR C677T TT genotype significantly increases the risk of MDD in males compared to females. Conclusion: These findings underscore the significant impact of genetic factors, particularly the association of MTHFR polymorphisms with MDD. The results highlight the importance of personalized treatment approaches considering individual genetic profiles.