Development of neuro-fuzzy model to explore gene–nutrient interactions modulating warfarin dose requirement. (August 2016)

• Record Type: Journal Article
• Authors: Pavani, Addepalli; Naushad, Shaik Mohammad; Lakshmitha, Ganapathy; Nivetha, Sriraman; Stanley, Balraj Alex; Malempati, Amaresh Rao; Kutala, Vijay Kumar
• Is Part Of: Pharmacogenomics. Volume 17:Number 12(2016)
• Page Start: 1315
• Page End: 1325
• Publication Date: 2016-08
• Subjects: CYP2C9 -- INR -- neuro-fuzzy model -- vitamin K -- VKORC1 -- warfarin; Pharmacogenomics -- Periodicals; 615.1
• DOI: 10.2217/pgs-2016-0058
• Languages: English
• ISSNs: 1462-2416

Abstract

Aim: To investigate the influence of alterations in vitamin K (K1, K2 and K3) in modulating warfarin dose requirement.Patients & methods: Reverse phase HPLC to determine the plasma vitamin K; PCR-RFLP to detect polymorphisms; and the neuro-fuzzy model to predict warfarin dose were used.Results: The developed neuro-fuzzy model showed a mean absolute error of 0.000024 mg/week. CYP2C9*2 and CYP2C9*3 mediated warfarin sensitivity was observed when vitamin K is in high and low tertiles, respectively. VKORC1 -1639G>A exhibited warfarin sensitivity in all combinations. Higher vitamin K1 was observed in CYP4F2 V433M polymorphism. The requirement of warfarin is low in GGCX 8016 GG genotype compared with GA and AA genotypes.Conclusion: Vitamin K profile along with genetic testing ensures precision in warfarin dose optimization.