BACKGROUND Psoriatic patients are at greater risk of oxidative stress and inflammation which is associated with abnormal plasma lipid metabolism and lipid peroxidation.There is not any information about the clinical significance of relation between methylentetrahydrofolatereductase (MTHFR) 677-T allele with malondialdehyde (MDA), lipids, apolipoproteins and vascular adhesion protein-1 (VAP-1) partakes in the migration process of lymphocytes into sites of inflammation. OBJECTIVES This study is the first investigation to examine the association of MTHFR (rs1801133) C677T polymorphism, serum level of MDA, VAP-1, lipid-lipoprotein and apolipoproteins with the risk of psoriasis. METHODS The present case-control study consisted of 100 psoriatic patients and 100 gender- and age-matched unrelated healthy controls from west population of Iran. MTHFR-C677T (rs1801133) polymorphisms were detected by restriction fragment length polymorphism (PCR-RFLP), VAP-1 by ELISA, apolipoproteins by immunoprecipitation, lipid and apolipoproteins by spectrophotometery and MDA by HPLC. RESULTS We found that dominant/recessive model (CC + CT/TT) and T allele of MTHFR-677 alleles significantly 7.45 and 1.76 times increased risk of psoriasis, respectively. The psoriasis patients with MTHFR-677-T (C/T + T/T) allele had significantly higher serum MDA, VAP-1 and apolipoproteinsAPOB concentrations and ratio of APOB/APOA1 than the control subjects.The MTHFR-677-T allele frequencies in psoriasis patients were significantly higher than that in control group (28.5% vs. 18.5%; P = 0.018).We found a significant positive correlation between VAP-1 with MDA (P = 0.047) and LP (a) (P = 0.025). CONCLUSION In the present study, we demonstrated for the first time that the psoriasis patients with MTHFR-677-T (C/T + T/T) allele had higher serum levels of MDA, VAP-1, APOB and ratio of APOB/APOA1 and dominant/recessive model (CC+CT/TT) and T allele of MTHFR-677 are significantly more common in psoriasis and increased risk of psoriasis by 7.45 and 1.76 fold, respectively. These data suggest that psoriasis patients carrying of TT genotypes and T allele of MTHFR-677 may be more susceptible to cardiovascular disease and myocardial infarction.