A Number Of Motives As to why AG-221 Is Greater As Compared To The Competitors

Variability of the L-Histidine decarboxylase gene in allergic rhinitis. Allergy 2010; 65: 1576�C1584. Background:? Nonsynonymous polymorphisms in RSL3 price genes coding for histamine-metabolizing enzymes, diamine oxidase and histamine N-methyltransferase are related to the risk of developing allergic diseases. The role of polymorphisms in the histidine decarboxylase gene remains unexplored. The objective of this study is to identify novel polymorphisms in the human histidine decarboxylase gene and to analyse the clinical association of nonsynonymous polymorphisms with rhinitis. Methods:? We performed a single-strand conformational polymorphism analysis of the histidine decarboxylase gene sequence. The presence of two nonsynonymous polymorphisms Thr31Met (rs17740607) and Glu644Asp (rs2073440) was analysed in 442 unrelated patients with allergic rhinitis, 233 of whom also had asthma, and in 486 healthy subjects. Results:? We observed three novel polymorphisms designated as ss50402829, ss50402830 and ss50402831-(rs17740607) with allele frequencies?=?0.005, 0.208 and 0.073, respectively. Statistically significant differences were observed for the histidine decarboxylase Glu644Asp AG-221 manufacturer (rs2073440) polymorphism, with OR (95% CI) values for homozygous carriers of the Glu644 allele equal to 3.12 (1.75�C5.56, P?Succimer with rhinitis?+?asthma (P?=?0.010). Conclusions:? The HDC allele Glu644 in homozygosity increases the risk of developing rhinitis in the studied population. This adds to increasing evidence supporting a prominent role of genetic variations related to histamine homeostasis in the risk to develop allergic diseases. Amongst biogenic amines, histamine (2-[4-imidazole]ethylamine) plays a prominent role in the regulation of numerous physiological and pathophysiological processes including gastric acid secretion, neurotransmission, hypersensitivity reactions, bronchial asthma, immune regulation and tumorigenesis (1�C3). Histamine is synthesized by decarboxylation of its precursor histidine in a one-step reaction carried out solely by the enzyme L-histidine decarboxylase (HDC, E.C. 4.1.1.22). This enzyme is encoded by the human HDC gene, which is located on chromosome 15q21-q22 and is composed of 12 exons spanning about 24?Kb (4). To date, a number of single-nucleotide polymorphisms (SNPs) have been identified for the human HDC gene in different human populations (5). However, little is known of the allele frequencies for these SNPs and whether variation in the HDC gene is related to the risk to develop, or to the clinical presentation of, allergic diseases.