Association of the Histamine N‐Methyltransferase C314T (Thr105Ile) Polymorphism with Atopic Dermatitis in Caucasian Children

Abstract

Study Objective-To investigate potential associations between the histamine Nmethyltransferase (HNMT) C314T (Thr105Ile) polymorphism and atopic dermatitis (AD) in a cohort of Caucasian children.Design-Prospective, multi-center (n=4) genotype/association study. Setting-Four academic, tertiary care, medical centers within the Pediatric Pharmacology Research Unit (PPRU) networkPatients or Participants-Caucasian children ages 6 months -5 years with (n=129) and without (n=127) AD. All subjects completed the study although data from 6 subjects (n=2 AD and n=4 control) were excluded due to violations in inclusion/exclusion criteria (n=5) and the informed consent process (n=1).Interventions-Information was collected regarding severity of AD, oral antihistamine treatment and treatment response via parental report. Buccal swabs (n=1 per cheek) were also performed to obtain epithelial cells for extraction of genomic DNA.Measurements and Main results-HMNT genotypes were successfully obtained in 116 and 122 control and AD subjects, respectively. Frequencies of the T314 variant allele (0.12, p=0.04) and combined CT/TT genotype (0.24, p=0.02) were significantly higher in children with AD compared with controls (allele and genotype frequencies = 0.06 and 0.12). Children with genotypes conferring reduced HNMT activity were two times more likely to have AD than those who were homozygous for the C314 reference allele.Conclusions-Increased histamine levels in patients with AD may result, at least in part, from reduced inactivation via HNMT. Genetically-associated reduction in histamine biotransformation may therefore contribute to the pathogenesis, persistence and progression of AD. If confirmed, these data indicate that HNMT might represent a common risk factor for development of AD, asthma and allergic rhinitis and may be useful in identifying individuals who are candidates for early preventative pharmacotherapeutic intervention. Additional longitudinal studies will be required in order to assess the relationship between genotype, disease severity and antihistamine response. NIH Public Access

Personalized medicine: A pediatric perspective

“…The frequency of the T314 variant allele was higher in children with atopic dermatitis than in controls (0.12 vs 0.06; P = 0.04). The combined frequency of genotypes associated with reduced HNMT activity (CT or TT) was also signifi cantly increased in children with atopic dermatitis compared with controls (0.24 vs 0.12; P = 0.02) [28]. Variation in the histamine metabolism pathway may provide another biologic pathway to predict disease and therapeutic response in children with atopic dermatitis, allergic rhinitis, and allergic asthma.…”

Drug interactions

“…However, it is not known whether this might contribute to pseudoallergic responses. Although polymorphisms of the HNMT gene do not appear to be associated with gastrointestinal diseases, recent data suggest that a mutation that gives rise to reduced histamine N-methyltransferase activity may be associated with atopic dermatitis (Kennedy et al, 2008).…”

Histaminintoleranz imitiert Anorexia nervosa

“…Die Histaminintoleranz tritt gehäuft bei Menschen mit atopischen Erkrankungen auf [2,5], wobei der Histaminüberschuss eine ähn-liche Symptomatik auslösen kann wie allergische Reaktionen. So wurden erhöhte Histaminkonzentrationen und erniedrigte DAO-Serumaktivitäten bei einer Subgruppe von Patienten mit atopischem Ekzem [5] sowie bei Patienten mit Nahrungsmittelallergie [4,7,8] gefunden; bei erstgenannter Patientengruppe gibt es bereits Hinweise auf eine genetische Grundlage [3]. Für andere atopische Erkrankungen wie allergisches Asthma bronchiale und allergische Rhinokonjunktivitis konnte dies bisher noch nicht gezeigt werden.…”