LDLR and ApoB are major genetic causes of autosomal dominant hypercholesterolemia in a Taiwanese population.
OBJECTIVE
Autosomal dominant hypercholesterolemia (ADH) is an autosomal dominant inherited disease characterized by an increase in low-density lipoprotein cholesterol levels and premature coronary heart disease, which can be caused by mutations in genes encoding the low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB) and proprotein convertase subtilisin/kexin type 9 (PCSK9). There is scant information with regard to the role played by each gene in the Taiwanese ADH population, especially the newly discovered PCSK9 gene.


METHODS
We used coupling heteroduplex analysis based on a denaturing high performance liquid chromatography system and DNA sequencing to screen for the LDLR gene, APOB gene and PCSK9 gene in 87 ADH cases recruited from 30 unrelated Taiwanese families.


RESULTS
We did not find any mutation-causing variant of the PCSK9 gene in our cases and thus excluded PCSK9 as the major culprit mutation in these families. On the other hand, we identified six previously reported LDLR gene mutations (C107Y, D69N, R385W, W462X, G170X, V408M), two novel LDLR gene mutations (FsG631 and splice junction mutation of intron 10), and one known mutation (R3500W) and one novel missense mutation (T3540M) in the APOB gene that were present in 55 members from 18 ADH families (60%). R3500W, rather than R3500Q, could be the principle mutation responsible for familial defective apolipoprotein B in Taiwanese.


CONCLUSIONS
The results of our study reveal a characteristic mutation pattern of ADH in Taiwan, mainly in the LDLR and APOB genes. However, PCSK9 gene mutation may not be a major cause of ADH in our study population.
Yang
Kai-Chien
KC
Division of Cardiology, Department of Internal Medicine, E-Da Hospital, Kaohsiung, Taiwan.
Su
Yi-Ning
YN
Shew
Jin-Yuh
JY
Yang
Kai-Ying
KY
Tseng
Wei-Kung
WK
Wu
Chau-Chung
CC
Lee
Yuan-Teh
YT
D000293:Adolescent; D000328:Adult; D000368:Aged; D001055:Apolipoproteins B / Q000235:genetics*; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011973:Receptors, LDL / Q000235:genetics*; D013624:Taiwan
D001055:Apolipoproteins B; D011973:Receptors, LDL