Genetic heterogeneity of autosomal dominant hypercholesterolemia

被引:152
作者
Varret, M. [1 ]
Abifadel, M. [1 ,2 ]
Rabes, J-P [3 ]
Boileau, C. [1 ,3 ]
机构
[1] Univ Paris 05, INSERM, U781, Hop Necker Enfants Malad, F-75015 Paris, France
[2] Univ St Joseph, Fac Pharm, Beirut, Lebanon
[3] Univ Versailles, AP HP, CHU Ambroise Pare, Lab Biochim & Genet Mol, Boulogne, France
关键词
ADH; APOB; apolipoprotein B-100; autosomal dominant hypercholesterolemia; genetic heterogeneity; LDLR; LDL receptor; mutation; PCSK9; proprotein convertase;
D O I
10.1111/j.1399-0004.2007.00915.x
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Autosomal dominant hypercholesterolemia (ADH) is characterized by isolated elevation of plasmatic low-density lipoprotein cholesterol associated with high risk of premature cardiovascular complications. More than 1000 mutations in the LDLR gene and 9 in the APOB gene have been implicated. We have shown further heterogeneity with the discovery of missense mutations in the PCSK9 gene resulting in ADH. Different studies have tried to evaluate the respective contribution of mutations in each gene to the disease, but results were not always in agreement. After a brief overview of mutations reported for each gene, strategies and results of these different studies are reviewed and analyzed. Altogether, numerous reports give evidence for the existence of a greater level of genetic heterogeneity in ADH and the involvement of still unknown genes.
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页码:1 / 13
页数:13
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