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 plasma HDL cholesterol and apolipoprotein AI concentration. At age 65, he had undergone triple vessel coronary bypass graft surgery. He had a strong family 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 in LCAT were present. We also evaluated plasma biochemistry and LCAT activity. Results: DNA sequencing revealed that the patient was a heterozygote for the 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 mutations in candidate genes, such as LCAT, can contribute to the spectrum of patients ascertained because of low HDL cholesterol.