ORIGINAL ARTICLE EPIDEMIOLOGY AND GENETICS Variability of the L-Histidine decarboxylase gene in allergic rhinitis G. Gervasini 1 *, J. A. G. Agu ´ ndez 1 *, J. Garcı´a-Menaya 2 , C. Martı´nez 1 , C. Cordobe ´s 3 , P. Ayuso 1 , J. A. Cornejo 4 , M. Blanca 5 & E. Garcı´a-Martı ´n 6 1 Department of Pharmacology, University of Extremadura, Badajoz; 2 Allergy Service, Infanta Cristina University Hospital, Badajoz; 3 Allergy Service, Hospital de Me ´ rida, Badajoz; 4 Fundacio ´ n Imabis, Ma ´ laga; 5 Allergy Service, Carlos Haya Hospital, Ma ´ laga; 6 Department of Biochemis- try & Molecular Biology & Genetics, University of Extremadura, Badajoz, Spain To cite this article: Gervasini G, Agu ´ ndez JAG, Garcı ´a-Menaya J, Martı ´nez C, Cordobe ´ s C, Ayuso P, Cornejo JA, Blanca M, Garcı ´a-Martı ´n E. Variability of the L-Histidine decarboxylase gene in allergic rhinitis. Allergy 2010; DOI: 10.1111/j.1398-9995.2010.02425.x. Amongst biogenic amines, histamine (2-[4-imidazole]ethyl- amine) plays a prominent role in the regulation of numerous physiological and pathophysiological processes including gastric acid secretion, neurotransmission, hypersensitivity reac- tions, bronchial asthma, immune regulation and tumorigenesis (1–3). Histamine is synthesized by decarboxylation of its pre- cursor 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 span- ning 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 Keywords histamine; histidine decarboxylase; polymorphism; rhinitis. Correspondence Elena Garcı ´a-Martı ´n, Department of Biochemistry & Molecular Biology & Genetics. University of Extremadura, Avda de Elvas s/n, 06071, Badajoz, Spain. Tel.: +34924289676 Fax: +34924289676 E-mail: elenag@unex.es *These authors contributed equally to the study. Accepted for publication 14 May 2010 DOI:10.1111/j.1398-9995.2010.02425.x Edited by: Marek Sanak Abstract Background: Nonsynonymous polymorphisms in genes coding for histamine-metab- olizing 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 (rs2073440) polymorphism, with OR (95% CI) values for homozygous carriers of the Glu644 allele equal to 3.12 (1.75–5.56, P < 0.00005) for all patients, 3.38 (1.54–7.44, P = 0.002) for patients with rhinitis alone, and 2.92 (1.43–5.95), P = 0.003 for patients with rhinitis + asthma, when compared with healthy controls. A significant Glu644 gene–dose effect was observed for overall patients (P = 0.0001), for patients with rhinitis alone (P = 0.005) and for patients with rhinitis + asthma (P = 0.010). Conclusions: The HDC allele Glu644 in homozygosity increases the risk of develop- ing 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. Abbreviations HDC, Histidine decarboxylase; SNP, Single-nucleotide polymorphism; SXR, Sinus X-ray; SSCP, Single-strand conformation polymorphism; DAO, Diamine oxidase; HNMT, Histamine N-methyltransferase. Allergy ª 2010 John Wiley & Sons A/S