Impact of Pharmacogenetic Variants in NAD⁺ Salvage Pathway Enzymes on Drug Response: A Personalized Medicine Perspective

The nicotinamide adenine dinucleotide (NAD⁺) salvage pathway plays a central role in cellular metabolism, redox balance, DNA repair, and gene regulation. In this article, we have comprehensively discussed the impact of pharmacogenetic variants in key NAD⁺ salvage pathway enzymes including NAMPT, NAPRT1, NMNAT1–3, NRK1/2, PARP1, CD38, and SIRT1 on drug response, efficacy, and toxicity. The NAD⁺ salvage pathway maintains cellular redox homeostasis, DNA repair, and metabolic regulation; thus, genetic variations in these enzymes can profoundly alter pharmacological outcomes. We have explored the physiological and biological importance of NAD⁺, its interaction with drug metabolism, and the comparative analysis of NAD⁺ biosynthesis routes. Furthermore, the article highlights how these variants influence drug efficacy and toxicity, emphasizing the role of companion diagnostics and pharmacogenetic testing in guiding personalized therapy. By integrating clinical and molecular data, this review underscores the potential of NAD⁺ pathway genotyping to improve treatment precision, reduce adverse reactions, and enhance patient-specific therapeutic success.