Cholesteryl ester transfer protein gene: Two common mutations and their effect on plasma high-density lipoprotein cholesterol content
- Hokkaido Univ. School of Medicine, Sapporo (Japan); and others
Cholesteryl ester transfer protein regulates high-density lipoprotein cholestrol (HDL-C) level, and genetic deficiency causes hyperalphalpoproteinemia (HALP). The G to A mutation in the intron 14 splice donor (I14A) has been known to be a common mutation in HALP. Recently, another mutant, D442G (Asp 442 to Gly), was ascertained. The allelic frequencies of I14A and D442G were investigated using 226 unrelated patients with HDL-C of 1.03 mmol/L (40 mg/dL) or greater. Of these, 44 had a mutation I14A and/or D442G. The I14A was found in 15, including 4 compound heterozygotes (I14A/D442G) in patients with HDL-C of 2.05 mmol/L (80 mg/dL) or greater. All I14A homozygotes (n = 5) were present in the group with HDL-C of 3.08 mmol/L (120 mg/dL) or greater, and the allelic frequency paralleled the increase in HDL-C level. D442G was identified in 33, including the 4 compound heterozygotes. Its allelic frequency appeared as two clusters, one at HDL-C around 1.79-2.03 mmol/L (70-79 mg/dL) and the other at HDL-C of 2.82 mmol/L (110 mg/dL) or greater; the latter consisted exclusively of compound heterozygotes. Allelic frequency in the general population for I14A and D442G was 0.81% and 4.62%, respectively. These data suggest that D442G is a common mutation and that although I14A is responsible for the most severe HALP, D442G leads to a relatively smaller increase in HDL-C. 19 refs., 1 fig., 3 tabs.
- OSTI ID:
- 183228
- Journal Information:
- Journal of Clinical Endocrinology and Metabolism, Vol. 79, Issue 6; Other Information: PBD: Dec 1994
- Country of Publication:
- United States
- Language:
- English
Similar Records
Expression of the human apolipoprotein A-I gene in transgenic mice alters high density lipoprotein (HDL) particle size distribution and diminishes selective uptake of HDL cholesteryl esters
Investigations on the transport and metabolism of high density lipoprotein cholesteryl esters in African green monkeys