Effects of NFKB1 gene polymorphism and frequently used drugs on the activation of nuclear factor κB (NF-κB)

The NF-κB signaling pathway plays a central role as an important interface between oxidative stress and inflammation. NF-κB activation is of high interest in various human diseases and in response to bioactive food compounds. The aim of this study was to elucidate effects of genetic background, age, gender and use of drugs on NF-κB activation. In the BIOCLAIMS cohort (1310 subjects, 606 M, 704 F, 18-85 y) (i) activation of p65 and p50, the most abundant NF-κB heterodimers; (ii) -94 ATTG insertion/deletion polymorphism in the promotor region of the NFKB1 gene; (iii) use of drugs with effects on NF-κB activation (renin-angiotensin-aldosterone system inhibitors, calcium channel blockers, statins, oral antidiabetics, acetylic salicylic acid; on-drug subjects, n=403), were determined. While p65 and p50 activation did not differ between genotypes in the entire study population (38.9% INS/INS, 46.3% INS/DEL and 14.8% DEL/DEL), there was a 14% higher p50 activation in DEL/DEL than in INS/DEL when on-drug subjects were excluded (P In conclusion, DEL/DEL carriers and subjects on frequently used drugs exhibit alterations in NF-κB activation that need to be taken into account in human studies.