Neuropeptide Y (NPY) and NPY Y2 receptor (Y2R) is involved in the stress-induced visceral obesity in mice. We have previously reported the association between 5'-flanking region of Y2R gene SNPs and plasma HDL-cholesterol levels in healthy subjects. Plasma HDL-cholesterol levels were significantly different in subjects with each SNPs (rs6857530; GG1.5-fold) 743 entities, and down-regulated (<0.67-fold) 492 entities of 54,675 probe sets. BIIE0246-upregulated genes significantly (P-value<0.001) related to gene ontology (GO) categories of 3 biological processes, 7 cellular components and 1 molecular function. Three biological processes were chylomicron remodeling, negative regulation of cholesterol and sterol transport. BIIE0246-downregulated genes significantly related to GO categories of 44 biological processes, 11 cellular components and 1 molecular function. Furthermore, BIIE0246-downregulated genes were significantly involved in 44 pathways (P<0.01), in which sterol responsive element binding protein signaling were included. BIIE0246-upregulated genes were significantly involved in 22 pathways including vitamin B12/ lipoprotein metabolism (P=0.0048). These results suggest that Y2R blockade might inhibit cholesterol synthesis and raise plasma HDL-cholesterol levels, suggesting a new therapeutic drug for dyslipidemia in subjects with specific Y2R SNPs.