Lack of association of NAMPT rs9770242 and rs59744560 polymorphisms with disease susceptibility and cardiovascular risk in patients with rheumatoid arthritis.

ABSTRACT

OBJECTIVES: Visfatin is an adipokine encoded by the NAMPT (PBEF1) gene. In this study we assessed the potential association of two NAMPT gene polymorphisms with disease susceptibility and cardiovascular (CV) risk in patients with rheumatoid arthritis (RA). METHODS: A total of 1,395 patients fulfilling the 1987 ACR classification criteria for RA and 1,230 matched controls, were genotyped for the NAMPT rs9770242 and rs59744560 gene polymorphisms, located within the proximal promoter, using predesigned TaqMan single nucleotide polymorphism genotyping assay. Also, HLA-DRB1 genotyping was performed using molecular based methods. In a second step, 1,196 patients in whom full information was available were assessed to determine the influence of NAMPT rs9770242 and rs59744560 polymorphisms in the development of CV events. Also, the potential influence of these polymorphisms in the development of subclinical atherosclerosis was assessed in a subgroup of patients with no history of CV events by brachial artery reactivity to determine flow-mediated endothelium-dependent and endothelium-independent vasodilatation (n=125) and by B-mode ultrasonography to determine the carotid artery intima-media thickness (n=105). RESULTS: No statistically significant differences in the allele or genotype frequencies for the NAMPT gene polymorphisms between RA patients and controls were found. A modest non significant lower frequency of the minor allele G of rs9770242 polymorphism was observed among patients with CV disease (20.62%) compared to those without CV disease (22.83%) (p=0.39). Also, a slight nonsignificant lower frequency of the minor allele T of rs59744560 polymorphism in patients with CV events (9.81%) compared with those RA patients who did not experience CV disease (13.07%) (p=0.11) was observed. Likewise, no significant association between the NAMPT polymorphisms with surrogate markers of subclinical atherosclerosis was found in patients with RA. CONCLUSIONS: NAMPT rs9770242 and rs59744560 polymorphisms are not markers of disease susceptibility and CV disease in RA.