Mutations in cholesteryl ester transfer protein and hepatic lipase in a North American population

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.