ABCB6 polymorphisms are not overly represented in patients with porphyria.
ABCB6 polymorphisms are not overly represented in patients with porphyria.
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DOI：
10.1182/bloodadvances.2021005484
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发表时间：
2022-02-08
期刊：
影响因子：
7.5
通讯作者：
Phillips JD
中科院分区：
文献类型：
--
作者：
Farrell CP;Nicolas G;Desnick RJ;Parker CJ;Lamoril J;Gouya L;Karim Z;Tchernitchko D;Chan B;Puy H;Phillips JD
ABCB6在细胞表面通过多个细胞器表达，但转运特异性尚不完全清楚。在所有类型的卟啉症中，与总体人群相比，ABCB6多态性并未过度代表。急性间歇性卟啉症、遗传性同比例卟啉症和多样性卟啉症的孟德尔遗传模式是常染色体显性的，但临床表型是异质性的。在一般人群中，外显率较低，但在有症状先证者的一级亲属中，外显率较高。这些观察结果表明，除了血红素生物合成途径中特定酶的突变外，遗传因素也有助于临床表型。最近的研究表明转运蛋白ABCB6的基因型与卟啉症表型有关。识别由ABCB6运输的分子一直是一个问题，并且导致了关于变异/突变如何或是否导致表型异质性的不确定性。Abcb6敲除小鼠模型还没有为研究提供方向，因为纯合子敲除动物没有离散表型。为了解决ABC6基因型和卟啉症表型之间的联系，我们分析了一大批急性肝性卟啉症和红细胞生成性原卟啉症患者。我们的研究表明，ABCB6基因型与疾病严重程度无关。因此，急性肝性卟啉症和红细胞生成性原卟啉症患者的ABCB6基因分型是不合理的。
ABCB6 is expressed on the cell surface and by multiple organelles, but transport specificity is incompletely understood. In all types of porphyria, ABCB6 polymorphisms are not overrepresented when compared with the overall population. The Mendelian inheritance pattern of acute intermittent porphyria, hereditary coproporphyria, and variegate porphyria is autosomal dominant, but the clinical phenotype is heterogeneous. Within the general population, penetrance is low, but among first-degree relatives of a symptomatic proband, penetrance is higher. These observations suggest that genetic factors, in addition to mutation of the specific enzyme of the biosynthetic pathway of heme, contribute to the clinical phenotype. Recent studies by others suggested that the genotype of the transporter protein ABCB6 contribute to the porphyria phenotype. Identifying the molecule(s) that are transported by ABCB6 has been problematic and has led to uncertainty with respect to how or if variants/mutants contribute to phenotypic heterogeneity. Knockout mouse models of Abcb6 have not provided a direction for investigation as homozygous knockout animals do not have a discrete phenotype. To address the proposed link between ABC6 genotype and porphyria phenotype, a large cohort of patients with acute hepatic porphyria and erythropoietic protoporphyria was analyzed. Our studies showed that ABCB6 genotype did not correlate with disease severity. Therefore, genotyping of ABCB6 in patients with acute hepatic porphyria and erythropoietic protoporphyria is not warranted.
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作者：
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