Identification and characterization of LDL receptor gene mutations in hyperlipidemic Chinese

Jui Hung Chang, Ju Pin Pan, Der Yan Tai, Ai Chun Huang, Pi Hung Li, Hui Ling Ho, Hui Ling Hsieh, Shiu Ching Chou, Wen Lang Lin, Eric Lo, Ching Yu Chang, Jerming Tseng, Ming Tsan Su, Guey Jen Lee-Chen*


研究成果: 雜誌貢獻期刊論文同行評審

38 引文 斯高帕斯(Scopus)


DNA screening for LDL receptor mutations was performed in 170 unrelated hyperlipidemic Chinese patients and two clinically diagnosed familial hypercholesterolemia patients. Two deletions (Del e3-5 and Del e6-8), eight point mutations (W-18X, D69N, R94H, E207K, C308Y, 1402T, A410T, and A696G), and two polymorphisms (A370T and I602V) were identified. Of these mutations, C308Y and Del e6-8 were found in homozygosity, and D69N and C308Y were seen in unrelated patients. The effects of mutations on LDL receptor function were characterized in COS-7 cells. The LDL receptor level and activity were close to those of wild type in A696G transfected cells. A novel intermediate protein and reduction of LDL receptor activity were seen in D69N transfected cells. For R94H, E207K, C308Y, I402T, and A410T mutations, only ∼20-64% of normal receptor activities were seen. Conversely, Del e3-5 and Del e6-8 lead to defective proteins with ∼0-13% activity. Most of the mutant receptors were localized intracellularly, with a staining pattern resembling that of the endoplasmic reticulum and Golgi apparatus (D69N, R94H, E207K, C308Y, and I402T) or endosome/lysosome (A410T and Del e6-8). Molecular analysis of the LDL receptor gene will clearly identify the cause of the patient's hyperlipidemia and allow appropriate early treatment as well as antenatal and family studies.

頁(從 - 到)1850-1858
期刊Journal of Lipid Research
出版狀態已發佈 - 2003 10月

ASJC Scopus subject areas

  • 生物化學
  • 內分泌
  • 細胞生物學


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