Cholesteryl ester transfer protein gene: two common mutations and their effect on plasma high-density lipoprotein cholesterol content
H Akita, H Chiba, K Tsuchihashi, M Tsuji, M Kumagai, K Matsuno and K Kobayashi
Department of Laboratory Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
Cholesteryl ester transfer protein regulates high-density lipoprotein
cholesterol (HDL-C) level, and genetic deficiency causes
hyperalphalipoproteinemia (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.
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