Genetics
A CETP mutation previously reported only once is surprisingly common in North Americans with high HDL cholesterol (Clin Biochem 1997)
Original title: Mutations in cholesteryl ester transfer protein and hepatic lipase in a North American population
This study examined seventy individuals with increased HDL-cholesterol (men above 1.7 mmol/L, women above 1.8 mmol/L) presenting to a North American Lipid Clinic, screening by PCR-RFLP for known mutations in CETP intron 14 and exon 15, and hepatic lipase (HL) exons 6 and 8. CETP intron 14 mutation frequency was 0.7% and CETP exon 15 A1503G was 0%, while HL exon 6 C873T was 2.1% and HL exon 8 C1221T was 0%. An unusual CETP exon 15 mutation, G1533A, predicting an arginine-to-glutamine change at position 451, was found at a frequency of 3.5%. The authors conclude known CETP mutations were much less prevalent in this North American population than previously reported in Japanese populations, HL mutations appear more prevalent than the six families previously described worldwide, and the CETP G1533A mutation, reported only once before, occurs here at a surprisingly high frequency of unknown functional significance.
Original abstract
Objective: To examine a North American population sample with increased HDL cholesterol for mutations in the genes coding for cholesteryl ester transfer protein (CETP) and hepatic lipase (HL).
Design And Methods: Seventy individuals with increased HDL cholesterol at the time of initial presentation to the Lipid Clinic (males > 1.7 mmol/L, females > 1.8 mmol/L) were examined by polymerase chain reaction-restriction fragment length polymorphism (PCR/RFLP) analysis for known mutations in CETP intron 14 and exon 15 and HL exons 6 and 8.
Results: CETP intron 14 mutation frequency 0.7%, CETP exon 15 A1503G 0%, HL exon 6 C873T 2.1%, HL exon 8 C1221T 0%. An unusual mutation in CETP exon 15 G1533A was found at a frequency of 3.5%. The sequence of this mutation was determined to be a G to A change at bp 1533 resulting in a predicted amino acid change of arginine to glutamine at position 451.
Conclusions: Known mutations in CETP were much less prevalent in this North American population than in the Japanese populations that have been previously reported. HL mutations, described previously in only 6 families worldwide, appear to be more prevalent than previously recognized. CETP G1533A, reported only once previously is prevalent in this population at a surprisingly high frequency. The functional significance of this mutation is unknown.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.