Journal
ALLERGY
Volume 65, Issue 12, Pages 1576-1584Publisher
WILEY
DOI: 10.1111/j.1398-9995.2010.02425.x
Keywords
histamine; histidine decarboxylase; polymorphism; rhinitis
Categories
Funding
- Fondo de Investigacion Sanitaria, Instituto de Salud Carlos III, Madrid, Spain [PS09/00943, PS09/00469, RETICS RD07/0064/0016]
- Junta de Extremadura, Merida, Spain [PRI07A005]
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Background: Nonsynonymous polymorphisms in 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 (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 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.
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