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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

38 Citations (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.

Original languageEnglish
Pages (from-to)1850-1858
Number of pages9
JournalJournal of Lipid Research
Issue number10
Publication statusPublished - 2003 Oct


  • Haplotype analysis
  • Low density lipoprotein receptor mutation
  • cDNA expression

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology


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