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Acetylation phenotype variation in pediatric patients with atopic dermatitis.
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MedLine Citation:
PMID:  21716538     Owner:  NLM     Status:  PubMed-not-MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Few studies have been done on the relation between acetylator status and allergic diseases.
AIM: To determine any possible association between acetylating phenotype in pediatric patients with atopic dermatitis (AD) and the disease prognosis.
PATIENTS AND METHODS: Thirty-six pediatric patients and forty two healthy children as a control group were participated in the study. All participants received a single oral dose of dapsone of 1.54 mg/kg body weight, after an overnight fast. Using high performance liquid chromatography (HPLC), plasma concentrations of dapsone and its metabolite (monoacetyldapsone) were estimated to phenotype the participants as slow and rapid acetylators according to their acetylation ratio (ratio of monoacetyldapsone to dapsone).
RESULTS: 72.2% of pediatric patients with AD showed slow acetylating status as compared to 69.4% of control individuals. Also, 73% of AD patients with slow acetylating phenotype had familial history of allergy. The severity of AD occurred only in slow acetylator patients. The eczematous lesions in slow acetylators presented mainly in the limbs, while in rapid acetylators, they were found mostly in face and neck.
CONCLUSION: This study shows an association between the N-acetylation phenotype variation and clinical aspects of AD.
Authors:
Rafi A Majeed Al-Razzuqi; Ali A Al-Jeboori; Makram M Al-Waiz
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Indian journal of dermatology     Volume:  56     ISSN:  1998-3611     ISO Abbreviation:  Indian J Dermatol     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-06-30     Completed Date:  2011-07-14     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  0370750     Medline TA:  Indian J Dermatol     Country:  India    
Other Details:
Languages:  eng     Pagination:  150-2     Citation Subset:  -    
Affiliation:
Department of Pharmacology and Therapeutics, College of Medicine, University of Baghdad, Baghdad, Iraq.
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Full Text
Journal Information
Journal ID (nlm-ta): Indian J Dermatol
Journal ID (publisher-id): IJD
ISSN: 0019-5154
ISSN: 1998-3611
Publisher: Medknow Publications, India
Article Information
© Indian Journal of Dermatology
open-access:
Received Month: 12 Year: 2009
Accepted Month: 7 Year: 2010
Print publication date: Season: Mar-Apr Year: 2011
Volume: 56 Issue: 2
First Page: 150 Last Page: 152
ID: 3108512
PubMed Id: 21716538
Publisher Id: IJD-56-150
DOI: 10.4103/0019-5154.80404

ACETYLATION PHENOTYPE VARIATION IN PEDIATRIC PATIENTS WITH ATOPIC DERMATITIS
Rafi A Majeed Al-Razzuqiaff1
Ali A Al-Jebooriaff1
Makram M Al-Waiz1
From the Department of Pharmacology and Therapeutics, College of Medicine, University of Baghdad, Baghdad, Iraq
1Department of Dermatology, College of Medicine, University of Baghdad, Baghdad, Iraq
Correspondence: Address for correspondence: Prof. Rafi A.Majeed Al-Razzuqi, Department of Pharmacology and Therapeutics, College of Medicine, University of Baghdad, Baghdad, Iraq. E-Mail: rafialmajeed@yahoo.com

Introduction

Atopic dermatitis (AD) is a common multifactorial disease characterized by an itchy, recurrent, flexural and symmetrical eczematous eruption.[1] Its frequency increases during childhood but it usually resolves by the age of 30 years.[2] Acetylation is a metabolic pathway in a number of drugs[3], which exhibits a genetically controlled bimodal distribution within any given population which is phenotyped as slow or rapid acetylators.[4] Studies had been done to determine acetylation phenotype in Middle East population,[58] which showed slow acetylator predominance. Therefore, we examined AD in this population to find any possible association with the disease severity.


Patients and Methods

Thirty-six pediatric patients, 21 males and 15 females, aged from 8 to 11 years (mean 9.66±0.9 SD) besides, 42 healthy children, 27 males and 15 females, aged from 7 to 11 years (mean 8.93±1.1 SD) as a control group, participated in this prospective and open study. Approval to conduct this study, was granted by the appropriate ethical committee in Baghdad College of Medicine. The participants were recruited from the outpatient clinic of Department of Dermatology of Baghdad Teaching Hospital from October 2007 to December 2008. Clinical diagnosis was done. The nature of the trial was explained to the children's parents and their consent was obtained. Then, Hanifin-Rajka scoring system[9] applied to evaluate the disease severity.

After an overnight fast, each individual (patient and control) received a single oral dose of dapsone 1.54 mg/kg body weight.[10] A blood sample (5 ml) was taken in a test tube containing heparin, 3 hours after the drug intake. Plasma was separated within 1 hour of collection and then high performance liquid chromatography (HPLC) was used to estimate plasma concentrations of dapsone and its metabolite (monoacetyldapsone).[10] Individuals were considered slow acetylators if their acetylation ratio (ratio of monoacetyldapsone to dapsone) was less than 0.30 and rapid acetylators if their acetylation ratio was greater than 0.30. Statistical analyses were done using SPSS version. The results were considered statistically significant if the P value was <0.05.


Results

Twenty-six of the 36 AD pediatric patients (72.2%) were slow acetylators compared with 29 of 42 control individuals (69.4%), and this was found to be a statistically non-significant result [Table 1]. In AD patients, a significant relationship appeared between familial history of allergy and slow acetylators who represented 73% (19 out of 26 slow acetylator patients) [Table 2]. Application of Hanifin-Rajka scoring system revealed that 30.5% (11 of 36 AD patients) were severe cases and all were slow acetylators [Table 3]. In the AD patients, eczematous lesions which presented in the limbs (elbows, knees, hands and feet) were found mostly in slow acetylators who represented 84.6% (22 out of 26 eczematous patients), whereas lesions that presented in the face and neck were found mainly in rapid acetylators who represented 60.0% (6 out of 10 rapid phenotypes). This showed a statistically significant difference [Table 4].


Discussion

This study demonstrated that there is a predominance of slow acetylators in AD patients as compared with the control group. The results are in accordance with those of studies that showed a predominance of AD patients carrying the allele for slow acetylation.[58]

However, our study succeeded to show a relation between acetylator status and different aspects of the disease course. A significant association was found between the severity of AD and slow acetylator status in which Hanifin-Rajka scoring system determined that a large number of slow acetylator AD patients had scores (≥ 50 points) which means severe cases, while no one is a rapid acetylator. This indicates that N-acetylation phenotype variation in human skin could account for variation in the disease severity. This result agreed with that of a study on acetylator phenotype among children with allergic contact dermatitis in which an association was found between the site of allergic lesions and acetylator status.[11]


Conclusion

In a population of slow acetylators, it appears that the slow acetylatation phenotype can be considered as a genetic predisposing state for AD and is a clue for severity of the disease.


Notes

Source of Support: Nil

Conflict of Interest: Nil.

References
1. William NM,Burney PG,Stracham D. Diagnostic criteria for atopic dermatitisBr J DermatolYear: 19941313974057918016
2. Schultz LF. Burr MLThe epidemiology of atopic dermatitisEpidemiology of clinical allergyYear: 1993BasalKargar928
3. Grant DM,Goodfelow GH,Sugamori K,Durette K. Pharmacogenetics of human arylamine N-acetyltransferasePharmacologyYear: 2000612041110971207
4. Lutz W. N-acetyltransferase genetic polymorphism and its role in developing of neoplastic conditionsMedYear: 20005127784
5. Ahmad RA. Acetylation in Iraqi populationFirst Scientific Congress, College of Medicine, University of BaghdadYear: 1984115
6. Rahman AH. Slow acetylator status in Iraqi people with Behcet's diseaseJ DermatolYear: 20023046471
7. Al-Yazigi A,Chaleby K,Martin CR. Acetylator phenotypes of Saudi Arabians using a simplified caffeine metabolites testEur J Clin PharmacoYear: 19892924650
8. Irshaid YM,Al-Hadidi HF,Latif A. The acetylator phenotypes in Jordanian diabeticsEur J Clin PharmacoYear: 1993346213
9. Larsen J,Jansens V,Morren M. Diagnostic features of atopic dermatitis through Hanifin-Rajka scoringBr J DermatolYear: 1995132167756118
10. Philip PA,Roberts MS,Rogers HJ. A rapid method for determination of acetylation phenotype using dapsoneBr J Clin PharmacoYear: 1984174659
11. Al-Razzuqi R. Acetylator Phenotype in Iraqi patients with allergyAnn Saudi MedYear: 200525473616438456

Tables
[TableWrap ID: T1] Table 1 

Frequency distribution of acetylation phenotype in AD patients and control



[TableWrap ID: T2] Table 2 

The acetylation phenotype and history of allergy in AD patients



[TableWrap ID: T3] Table 3 

The acetylation phenotype and Hanifin-Rajka scoring system in AD patients



[TableWrap ID: T4] Table 4 

The acetylation phenotype and distribution of eczematous lesions in AD patients




Article Categories:
  • Basic Research

Keywords: Acetylation phenotype, atopic dermatitis, Hanifin-Rajka scoring system, monoacetyldapsone.

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