The 16189 variant of mitochondrial DNA occurs more frequently in C282Y homozygotes with haemochromatosis than those without iron loading
The 16189 variant of mitochondrial DNA occurs more frequently in C282Y homozygotes with haemochromatosis than those without iron loading
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DOI：
10.1136/jmg.2003.008805
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发表时间：
2004-01-01
影响因子：
4
通讯作者：
Robson, KJH
中科院分区：
文献类型：
--
作者：
Livesey, KJ;Wimhurst, VLC;Robson, KJH
背景：遗传性血色病（HH）患者通常是HFE基因C282Y突变的纯合子。他们有不同的铁超载表达，并表现出多种并发症，包括肝病、糖尿病、关节病、疲劳和心肌病。线粒体16189变异与糖尿病、扩张型心肌病和出生时低体脂有关，并可能导致进一步多因素疾病的遗传易感性。本研究的目的是确定16189变异在一系列HFE基因突变的血色素沉着病患者中的频率。方法：分析英国、法国和澳大利亚C282Y纯合子和已知铁状态的对照以及出生队列中存在16189变异的血液DNA。结果：与人群对照和无症状的C282Y纯合子相比，C282Y等位基因纯合子的血色素沉着病患者线粒体16189变异频率升高(42/292 (14.4%)；102/1186 (8.6%) (p = 0.003)；2/64 (3.1%) （p = 0.023）。结论：16189线粒体变体的存在加重了与HH的C282Y纯合子的铁负荷。
Background: Patients with hereditary haemochromatosis (HH) are usually homozygous for the C282Y mutation in the HFE gene. They have variable expression of iron overload and present with a variety of complications, including liver disease, diabetes, arthropathy, fatigue, and cardiomyopathy. The mitochondrial 16189 variant is associated with diabetes, dilated cardiomyopathy, and low body fat at birth, and might contribute to genetic predisposition in further multifactorial disorders. The objective of this study was to determine the frequency of the 16189 variant in a range of patients with haemochromatosis, who had mutations in the HFE gene.Methods: Blood DNA was analysed for the presence of the 16189 variant in British, French, and Australian C282Y homozygotes and controls, with known iron status, and in birth cohorts.Results: The frequency of the mitochondrial 16189 variant was found to be elevated in individuals with haemochromatosis who were homozygous for the C282Y allele, compared with population controls and with C282Y homozygotes who were asymptomatic (42/292 (14.4%); 102/1186 (8.6%) ( p = 0.003); and 2/64 (3.1%) ( p = 0.023), respectively).Conclusions: Iron loading in C282Y homozygotes with HH was exacerbated by the presence of the mitochondrial 16189 variant.