Lecithin : cholesterol acyl transferase G30S: association with atherosclerosis, hypoalphalipoproteinemia and reduced in vivo enzyme activity

Objectives: A 69 yr old male was referred for assessment of a very low plas ma HDL cholesterol and apolipoprotein AI concentration. At age 65, he had u ndergone triple vessel coronary bypass graft surgery. He had a strong famil y history of early coronary heart disease. We analyzed the molecular basis of his clinical and biochemical abnormalities. Design and methods: We used DNA sequencing to determine whether mutations i n LCAT were present. We also evaluated plasma biochemistry and LCAT activit y. Results: DNA sequencing revealed that the patient was a heterozygote for th e G30S mutation in the gene encoding lecithin: cholesteol acyl transferase (LCAT). His plasma was found to have half-normal LCAT activity. Conclusions: The findings in this patient suggest that rare dysfunctional m utations in candidate genes, such as LCAT, can contribute to the spectrum o f patients ascertained because of low HDL cholesterol. (C) 2001 The Canadia n Society of Clinical Chemists. All rights reserved.