Expression of Mutations in the Low-density Lipoprotein Receptor Gene Associated with Familial Hypercholesterolemia in Taiwan

家族性高膽固醇血症（FH）為低密度脂蛋白（LDL）受體突變導致的體染色體顯性遺傳疾病。先前於台灣FH患者中發現五種LDL受體基因的點突變（D69N、C308Y、1402T、A410T、A696G），本研究即對這些突變做初步記述。野生型的LDL受體cDNA被選殖入真核表現載體，含上述突變的cDNA重組質體亦被構築。在轉移的COS-7細胞中，野生型的cDNA表現160 kDa成熟蛋白及少量的120 kDa前驅蛋白。含D69N突變的重組質體表現的LDL受體mRNA量明顯的降低，且出現異常的中間型前驅蛋白。合C308Y、I402T及A410T突變的重組質體所表現的mRNA量與野生型者相近，但所表現的成熟蛋白與前驅蛋白的比值均較野生型者少。合A696G的mRNA及成熟蛋白則均與野生型者相近。此LDL受體基因的分生研究可明確的定義患者的高血脂原因及進行出生前診斷、家族分析等。

關鍵字

低密度脂蛋白受體突變； cDNA表現

並列摘要

Familial hypercholesterolemia (FH) is an autosomal dominant disorder of lipoprotein metabolism, primarily caused by mutation in the low-density lipoprotein (LDL) receptor gene. Previously five point mutations (D69N, C308Y, I402T, A410T, and A696G) in the LDL receptor gene were identified in Taiwanese patients with FH. The preliminary characterization of these mutations is reported here. The wild type LDL receptor eDNA was subcloned into eukaryotic expression vector and cDNAs containing the five mutations were constructed. In transfected COS-7 cells, the wild type eDNA expressed 160 kDa mature and 120 kDa precursor proteins. An apparent reduction in LDL receptor mRNA level and a novel intermediate protein were seen in D69N transfected cells. Although normal amount ofLDL receptor mRNA was seen with the C308Y, I402T and A410T mutations, the amount of mature protein versus precursor protein was less than in the wild type. The LDL receptor mRNA and protein levels were close to those of wild type in A696G transfected cells. Molecular analysis of the LDL receptor gene can define the cause of patient's hyperlipidemia clearly and allow appropriate early treatment as well as antenatal and family studies.

並列關鍵字

LDL receptor mutations ； cDNA expression

國際替代計量

Expression of Mutations in the Low-density Lipoprotein Receptor Gene Associated with Familial Hypercholesterolemia in Taiwan

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