Association of the Histamine N-Methyltransferase C314T (Thr105Ile) Polymorphism with Atopic Dermatitis in Caucasian Children
Association of the Histamine N-Methyltransferase C314T (Thr105Ile) Polymorphism with Atopic Dermatitis in Caucasian Children
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DOI：
10.1592/phco.28.12.1495
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发表时间：
2008-12-01
期刊：
影响因子：
4.1
通讯作者：
Hein, David W.
中科院分区：
文献类型：
--
作者：
Kennedy, Mary Jayne;Loehle, Jennifer A.;Hein, David W.
研究目的。在一组白人儿童中研究组胺N-甲基转移酶（HNMT）基因、HNMT、C314 T（Thr 105 Ile）多态性与特应性皮炎之间的潜在关联。前瞻性、多中心、基因型关联研究。四个学术，三级保健医疗中心内的儿科药理学研究单位网络。249名6个月至5岁的白人儿童患有特应性皮炎（127名患者）或无特应性皮炎（122名对照受试者）。进行颊拭子（一个拭子/颊）以获得用于提取基因组DNA的上皮细胞。通过父母报告收集关于特应性皮炎严重程度、口服抗组胺药治疗和治疗反应的数据。在116名对照受试者和122名特应性皮炎患者中成功获得HNMT基因型。与对照组相比，特应性皮炎患儿中T314变异等位基因（0.1.2 vs 0.06，P=0.04）和CT/TT联合基因型（0.24 vs 0.1.2，P=0.02）的频率显著较高。携带HNMT活性降低基因型的儿童患特应性皮炎的可能性是携带C314参考等位基因纯合子的儿童的2倍。特应性皮炎患者组胺水平升高可能至少部分是由于HNMT导致酶失活减少。因此，遗传相关的组胺生物转化减少可能有助于特应性皮炎的发病机制，持续性和进展。如果得到证实，这些数据表明，HNMT基因型可能是一个共同的危险因素发展的特应性皮炎，哮喘和过敏性鼻炎，并可能是有用的，在确定个人谁是候选人的早期预防性药物干预。需要进一步的纵向研究来评估基因型、疾病严重程度和抗组胺药反应之间的关系。
Study Objective. To investigate potential associations between the histamine N-methyltransferase (HNMT) gene, HNMT, C314T (Thr105Ile) polymorphism and atopic dermatitis in a cohort of Caucasian children.Design. Prospective, multicenter, genotype-association studySetting. Four academic, tertiary care medical centers within the Pediatric Pharmacology Research Unit network.Participants. Two hundred forty-nine Caucasian children aged 6 months-5 years with atopic dermatitis (127 patients) or without (122 control subjects).Intervention. Buccal swabs (one swab/cheek) were performed to obtain epithelial cells for extraction of genomic DNA.Measurements and Main Results. Data were collected on severity of atopic dermatitis, oral antihistamine treatment, and treatment response through parental report. The HNMT genotypes were successfully obtained in 116 control subjects and 122 patients with atopic dermatitis. Frequencies of the T314 variant allele (0.1.2 vs 0.06, P=0.04) and combined CT/TT genotype (0.24 vs 0.1.2, p=0.02) were significantly higher in children with atopic dermatitis compared with control subjects. Children with genotypes conferring reduced HNMT activity were 2 times more likely to have atopic dermatitis than those who were homozygous for the C314 reference allele.Conclusion. Increased histamine levels in patients with atopic dermatitis may result, at least in part, from reduced enzymatic inactivation via HNMT. Genetically associated reduction in histamine biotransformation may therefore contribute to the pathogenesis, persistence, and progression of atopic dermatitis. If confirmed, these data indicate that HNMT genotype might represent a common risk factor for development of atopic dermatitis, asthma, and allergic rhinitis and may be useful in identifying individuals who are candidates for early preventive pharmacotherapeutic intervention. Additional longitudinal studies will be required to assess the relationship between genotype, disease severity, and antihistamine response.