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


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.
Rosset
J
J
The John P. Robarts Research Institute and Department of Medicine, University of Western Ontario, London, Ontario, Canada.
Wang
J
J
Wolfe
B M
BM
Dolphin
P J
PJ
Hegele
R A
RA
D000368:Aged; D019943:Amino Acid Substitution; D016632:Apolipoprotein A-I / Q000097:blood; D001161:Arteriosclerosis / Q000150:complications / Q000201:enzymology* / Q000235:genetics; D008076:Cholesterol, HDL / Q000097:blood; D004591:Electrophoresis, Polyacrylamide Gel; D006579:Heterozygote; D006801:Humans; D008297:Male; D009154:Mutation; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000097:blood* / Q000235:genetics; D015183:Restriction Mapping; D017422:Sequence Analysis, DNA; D013631:Tangier Disease / Q000150:complications / Q000201:enzymology*
D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; D007862:Phosphatidylcholine-Sterol O-Acyltransferase