A common mutation in cholesteryl ester transfer protein gene and plasma HDL cholesterol level before and after hormone replacement therapy in Korean postmenopausal women

BACKGROUND: Plasma cholesteryl ester transfer protein (CETP) functions to transfer cholesteryl ester from HDL to triglyceride-rich lipoproteins and regulates plasma HDL cholesterol level. A common mutation, the exon 15 A to G substitution at codon 442 (D442G) results in reduced plasma CETP activity and increased plasma HDL cholesterol level. Meanwhile, hormone replacement therapy (HRT) in postmenopausal women increases plasma HDL cholesterol level. METHODS: We investigated the frequency of D442G mutation and its effect on plasma HDL cholesterol level in Korean women. We also examined if the mutation has any effect on an increase in plasma HDL cholesterol level during HRT. RESULTS: Two hundred and twenty eight women aged over 40 years were recruited in this study. Of 228 women, 22 (9.6%) were identified as having the D442G mutation; 21 heterozygotes and 1 homozygote. The subjects with the mutation had higher plasma HDL cholesterol levels than those without the mutation (61.6 +/- 17.3 vs. 55.1 +/- 14.0 mg/dL, p < 0.05). After 12 month HRT, HDL cholesterol increased by 6.4% (3.6 +/- 13.2 mg/dL, p < 0.05) and D442G mutation did not have any significant effect on the change of plasma HDL cholesterol level. CONCLUSION: D442G mutation is common in Korean postmenopausal women and it is associated with increased plasma HDL cholesterol level. HRT for postmenopausal women increased plasma HDL cholesterol level in similar amounts regardless of the presence or absence of D442G mutation.

CETP(Cholesteryl Ester Transfer Protein) Deficiency Caused by Genetic Mutation in the CETP Gene in Normal Korean Population

BACKGROUND: CETP(Cholesteryl ester transfer Protein) is the essential protein for 'reverse cholesterol transport' which transfers cholesteryl ester from HDL particles to other lipoproteins. The subjects with CETP deficiency caused by genetic mutation in the CETP gene have very high HDL levels that CETP deficiency implies anti-atherogenic effect. A missense mutation in the exon 15(D442G) and a splicing defect in the intron 14(Int 14A) in the CETP gene are reported to be popular among Japanese population which overall prevalence of both mutations is up to 10%. METHODS: To identify the CETP mutaion such as D442G or Int 14A among Koreans, seven subjects who have high HDL level above 80mg/dl and 14 first-degree relatives of them were included in this study. RESULTS: Of 21 subjects in 7 familes, 5 subjects in 2 families were confirmed as D442G mutation of CETP gene, but Int 14A mutation is not found. Subjects with D442G mutation have high apo A-I levels as well as HDL levels. CONCLUSION: The D442G mutation of CETP gene is firstly confirmed in Koreans. The CETP deficiency caused by genetic mutation in the CETP gene seems to be prevalent among Korean population.