Zielińska E, Niewiarowski W, Bodalski J, Stańczyk A, Bolanowski W, Rebowski G
Second Clinic of Pediatrics, Medical University of Lódź, Poland.
Clin Pharmacol Ther. 1997 Dec;62(6):635-42. doi: 10.1016/S0009-9236(97)90083-7.
The overrepresentation of phenotypically slow acetylators among patients with atopic allergy has been reported in previous studies. The N-acetyltransferase coding gene has not yet been investigated in allergic diseases. This study was designed to determine the differences in the distribution of mutation frequency and genotypes that encode normal and defective activity of N-acetyltransferase in children with atopic allergies compared with healthy children. In 56 children with documented inhalational, food, or mixed allergies and in 100 healthy control children with no clinical or laboratory signs of allergy, the genotype coding for N-acetyltransferase was identified by means of the polymerase chain reaction followed by analysis of restriction fragment length polymorphism. Nucleotide transitions in the following positions were investigated: 481 C-->T, 590 G-->A, 803 A-->G, and 857 G-->A, which enabled the identification of six genotypes, including the wild-type (wt) allele, and 16 genotypes, including mutated alleles (homozygotic and herterozygotic). The statistical analysis showed significant differences in the distribution of the frequency of the occurrence of mutated alleles and genotypes between the two groups of children. In 51 children (91%) with allergy, genotypes that encode acetylation defect were found; genotypes that code for normal N-acetyltransferase were observed in only five allergic children (9%). In the control group the distribution of genotypes coding for normal and defective N-acetyltransferase activity is 38% and 62%, respectively. Thus study enabled the conclusion that the slow acetylation genotype is a genetic marker of predisposition to atopy.
先前的研究报道了特应性过敏患者中表型慢乙酰化者的比例过高。N - 乙酰转移酶编码基因尚未在过敏性疾病中进行研究。本研究旨在确定与健康儿童相比，特应性过敏儿童中编码正常和缺陷活性的N - 乙酰转移酶的突变频率和基因型分布的差异。在56名有吸入性、食物性或混合性过敏记录的儿童和100名无临床或实验室过敏迹象的健康对照儿童中，通过聚合酶链反应，随后分析限制性片段长度多态性来鉴定编码N - 乙酰转移酶的基因型。研究了以下位置的核苷酸转换：481 C→T、590 G→A、803 A→G和857 G→A，这使得能够鉴定包括野生型（wt）等位基因在内的6种基因型，以及包括突变等位基因（纯合子和杂合子）在内的16种基因型。统计分析显示两组儿童之间突变等位基因和基因型出现频率的分布存在显著差异。在51名（91%）过敏儿童中，发现了编码乙酰化缺陷的基因型；仅在5名过敏儿童（9%）中观察到编码正常N - 乙酰转移酶的基因型。在对照组中，编码正常和缺陷N - 乙酰转移酶活性的基因型分布分别为38%和62%。因此，本研究得出结论，慢乙酰化基因型是易患特应性的遗传标志物。
