Genetics
Three novel CETP gene mutations identified in Japanese patients with hyperalphalipoproteinemia (Clin Chim Acta 2012)
Original title: Novel mutations of cholesteryl ester transfer protein (CETP) gene in Japanese hyperalphalipoproteinemic subjects
Researchers sequenced the CETP gene in Japanese subjects with hyperalphalipoproteinemia (HALP), a condition often caused by CETP mutations, to identify variants beyond the two most common ones (D442G and Intron 14 +1G>A). Three subjects carried novel mutations: a compound heterozygote for c.653_654delGGinsAAAC and the Intron 14 splicing mutation, a heterozygote for c.658G>A, and a homozygote for L261R. Functional studies in transfected COS-1 cells confirmed that c.658G>A, located at the last nucleotide of exon 7, causes a splicing abnormality, and that L261R CETP protein was not secreted into the culture media. The authors conclude these three novel mutations cause HALP through CETP deficiency and predict additional rare CETP mutations remain to be found in the Japanese population.
Original abstract
Background: The half of hyperalphalipoproteinemia (HALP) in Japan is caused by CETP gene mutations. Other than two prevalent mutations (D442G and Intron 14 splicing donor site +1G>A), some rare CETP mutations are found in Japanese HALP subjects.
Methods: CETP gene analysis of genomic DNA from subjects was performed by restriction fragment length polymorphism (RFLP) and sequencing analysis. Mutations which were suspected to cause a splicing defect or a protein secretion defect were investigated in COS-1 cells transfected with a CETP minigene construct or a cDNA expression vector.
Results: Each of three subjects was identified as a carrier of CETP gene mutation of a compound heterozygote of c.653_654delGGinsAAAC and Intron 14 splicing donor site +1G>A, a heterozygote of c.658G>A or a homozygote of L261R. The c.658G>A mutation was located at the last nucleotide of exon 7, and it was confirmed to cause splicing abnormality revealed by the CETP minigene analysis. The L261R CETP was not secreted to conditioned media of the cells.
Conclusions: Three novel CETP gene mutations are responsible for HALP by CETP deficiency. It is predicted that there are more rare CETP gene mutations in Japanese, and these multiple rare mutations alone or a combination with each of prevalent mutations is responsible for mild-to-moderate or marked HALP, respectively.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.