爱尔兰人群中HFE基因Cys 282 Tyr突变的高发生率——对血色素沉着症的影响

High incidence of the Cys 282 Tyr mutation in the HFE gene in the Irish population--implications for haemochromatosis.

作者信息

Murphy S, Curran M D, McDougall N, Callender M E, O'Brien C J, Middleton D

机构信息

Northern Ireland Histocompatibility and Immunogenetics Laboratory, Belfast City Hospital, Belfast.

出版信息

Tissue Antigens. 1998 Nov;52(5):484-8. doi: 10.1111/j.1399-0039.1998.tb03076.x.

DOI:10.1111/j.1399-0039.1998.tb03076.x

PMID:9864039

Abstract

A simple PCR-SSOP approach based on a single PCR product has been developed to screen the HFE gene for the haemochromatosis-associated mutations Cys 282 Tyr and His 63 Asp. Using this approach the prevalence of these mutations in a cohort (30) of haemochromatosis patients and normal controls (404) was determined. Ninety percent of the haemochromatosis patients were homozygous for the Cys 282 Tyr mutation. In the normal population we found an increased incidence of the Cys 282 Tyr mutation (17.3%; 95% confidence limits 0.136-0.209) which was also reflected in the higher frequency of Cys 282 Tyr homozygotes (1.24%; 95% confidence limits 0.0016-0.0232). Linkage disequilibrium analysis confirmed the association between A03 and Cys 282 Tyr. However, strong linkage disequilibrium occurred with the HLA-A03-associated allele HLA-B14 but not the HLA-A03-associated allele HLA-B07. The His 63 Asp was found to be in linkage disequilibrium with HLA-A29.

摘要

已开发出一种基于单个PCR产物的简单PCR-SSOP方法，用于筛查HFE基因中与血色素沉着症相关的突变Cys 282 Tyr和His 63 Asp。使用该方法确定了这些突变在一组血色素沉着症患者（30例）和正常对照（404例）中的患病率。90%的血色素沉着症患者为Cys 282 Tyr突变纯合子。在正常人群中，我们发现Cys 282 Tyr突变的发生率增加（17.3%；95%置信区间0.136-0.209），这也反映在Cys 282 Tyr纯合子的较高频率上（1.24%；95%置信区间0.0016-0.0232）。连锁不平衡分析证实了A03与Cys 282 Tyr之间的关联。然而，与HLA-A03相关的等位基因HLA-B14发生了强连锁不平衡，而与HLA-A03相关的等位基因HLA-B07未发生。发现His 63 Asp与HLA-A29处于连锁不平衡状态。