Anvari Sara, Vyhlidal Carrie A, Dai Hongying, Jones Bridgette L
1 Division of Allergy/Asthma/Immunology.
2 Children's Mercy Hospital, and.
Am J Respir Cell Mol Biol. 2015 Dec;53(6):802-9. doi: 10.1165/rcmb.2014-0493OC.
Histamine is an important mediator in the pathogenesis of asthma. Variation in genes along the histamine production, response, and degradation pathway may be important in predicting response to antihistamines. We hypothesize that differences exist among single-nucleotide polymorphisms (SNPs) in genes of the histamine pathway between children with allergic versus nonallergic asthma. Children (7-18 yr of age; n = 202) with asthma were classified as allergic or nonallergic based on allergy skin testing. Genotyping was performed to detect known SNPs (n = 10) among genes (HDC, HNMT, ABP1, HRH1, and HRH4) within the histamine pathway. Chi square tests and Cochran-Armitage Trend were used to identify associations between genetic variants and allergic or nonallergic asthma. Significance was determined by P < 0.05 and false-positive report probability. After correction for race differences in genotype were observed, HRH1-17 TT (6% allergic versus 0% nonallergic; P = 0.04), HNMT-464 TT (41% allergic versus 29% nonallergic; P = 0.04), and HNMT-1639 TT (30% allergic versus 20% nonallergic; P = 0.04) were overrepresented among children with allergic asthma. Genotype differences specifically among the African-American children were also observed: HRH1-17 TT (13% allergic versus 0% nonallergic; P = 0.04) and HNMT-1639 TT (23% allergic versus 3% nonallergic; P = 0.03) genotypes were overrepresented among African-American children with allergic asthma. Our study suggests that genetic variation within the histamine pathway may be associated with an allergic versus nonallergic asthma phenotype. Further studies are needed to determine the functional significance of identified SNPs and their impact on antihistamine response in patients with asthma and allergic disease.
组胺是哮喘发病机制中的一种重要介质。组胺产生、反应及降解途径相关基因的变异在预测抗组胺药反应方面可能具有重要意义。我们推测，过敏性哮喘儿童与非过敏性哮喘儿童在组胺途径基因的单核苷酸多态性（SNP）上存在差异。根据过敏皮肤试验，将哮喘儿童（7 - 18岁；n = 202）分为过敏性或非过敏性。进行基因分型以检测组胺途径内基因（HDC、HNMT、ABP1、HRH1和HRH4）中的已知SNP（n = 10）。采用卡方检验和 Cochr an - Armitage趋势检验来确定基因变异与过敏性或非过敏性哮喘之间的关联。显著性通过P < 0.05和假阳性报告概率来确定。校正种族差异后观察到基因型差异，HRH1 - 17 TT（过敏性6%对非过敏性0%；P = 0.04）、HNMT - 464 TT（过敏性为41%对非过敏性29%；P = 0.04）和HNMT - 1639 TT（过敏性30%对非过敏性20%；P = 0.04）在过敏性哮喘儿童中占比过高。在非裔美国儿童中也观察到了特定的基因型差异：HRH1 - 17 TT（过敏性13%对非过敏性0%；P = 0.04）和HNMT - 1639 TT（过敏性23%对非过敏性3%；P = 0.03）基因型在患有过敏性哮喘的非裔美国儿童中占比过高。我们的研究表明，组胺途径内的基因变异可能与过敏性和非过敏性哮喘表型相关。需要进一步研究以确定已鉴定SNP的功能意义及其对哮喘和过敏性疾病患者抗组胺药反应的影响。
