Apolipoprotein C-II promoter T → A substitution at position −190 affects on the transcription of the gene and its relationship to hyperlipemia

A Chinese patient with severe hypertriglyceridemia was found to have similar clinical features to that of malignant hyperlipemia in infancy. DNA sequence analysis of the apoC-II gene from the patient’s parents revealed a novel heterozygous mutation of T → A substitution at position −190 base in the apoC-II promoter. We speculated that the patient was a homozygote of the same mutation that resulted in the deficiency of apoC-II. In vitro expression studies showed T → A substitution in the apoC-II promoter leads to a decrease by approximately 20% in transcriptional activity compared with its counterpart that inserted the normal promoter. These results suggested that T → A substitution at position −190 in the apoC-II gene promoter only partly affected transcriptional activity of the apoC-II promoter, leading to decrease of apoC-II expression in quantity.