A study of ACE, eNOS and MTHFR association with psoriasis in Pakistani population

Psoriasis is chronic inflammatory skin disease characterized by scaly skin, which affects 24% population globally. Role of different SNPs among ACE (angiotensin converting enzyme), eNOS (Endothelial nitric oxide synthase) and MTHFR (Methyltetrahydrofolate reductase) has been established in different genetic disorders, till date there is very limited data available which quadrate the role of these important genes in the pathogenesis of Psoriasis. The present study was conducted to determine the association of ACE, eNOS and MTHFR polymorphisms with psoriasis in the Pakistani population. A total of 240 psoriatic patients and 264 healthy controls were genotyped by polymerase chain reaction (PCR) for rs464699 Insertion/Deletion (ID) polymorphism in intron 16 of ACE, rs869109213 VNTR (a/b) polymorphism in intron 4 of eNOS and by restriction fragment length polymorphism (RFLP) for rs2274976 G1793A, rs1801133 C677T and rs1801131 A1298C of MTHFR. In order to statistically analyze the genotype-phenotype association, logistic regression analysis was applied to the genotype data of psoriatic patients and controls. The ACE genotype DD was found to be significantly associated with risk of psoriasis (Odds Ratio [OR] = 1.93(95% Confidence Interval [CI] = 1.25-2.98), p= 0.02) under the recessive model. eNOS (a/b) polymorphism also demonstrated association with susceptibility to risk of psoriasis in the current cohort (OR = 1.88 (95% CI = 1.25-2.83), p = 0.001) under dominant model. In the case of MTHFR rs2274976 revealed significant association with psoriasis (OR = 2.93 (95% CI = 1.88-4.58) p ≤ 0.001) under the dominant model as well as the recessive model (OR = 1.34 (95% CI = 1.34-15.04) p = 0.005). rs1801133 also had marginal association with psoriasis by conferring protection against disease susceptibility under the dominant model (OR = 0.63 (95% CI = 0.4-1.0) p ≤ 0.05), while rs1801131 did not show any association with psoriasis. In conclusion, in the Pakistani population ACE (ID), eNOS (a/b) and MTHFR G1793A polymorphism were observed to be significantly associated with the disease.