Familial hypercholesterolemia (FH) is genetically autosomal dominant disease and is most often caused by mutations in the low-density lipoprotein receptor (LDLR) gene. The Taiwanese Survey on Hypertension, Hyperglycemia, and Hyperlipidemia (TwSHHH) in 2002 revealed that hypercholesterolemia, defined as cholesterol level at or above 240 mg/dL, accounted for 10.9% (Male: 10.8% and female: 10.9%) of 315 years-old age population in Taiwan. According to the modified Simon Broome criteria, the estimated prevalence of phenotypic familial hypercholesterolemia (FH) from data of 2002 TwSHHH is 0.62%, about one in 160 among Taiwanese population. The high prevalence of FH in Taiwan indicated the urgent need of public health concern and development of strategy in the prevention and management of atherosclerotic disorders and cardiovascular complications associated with hypercholesterolemia. However, investigation of genetic mutations and ethnicity among FH in Taiwanese are still rare reported.
　　 The mutations of FH were investigated from 2002 through 2011 in National Taiwan University Hospital (NTUH). We recruited 100 index patients with cholesterol level ?290 mg/dL and LDL-cholesterol ? 190 mg/dL and at least one family member with the same criteria for genetic study of FH. The study applied strategy of cascade screening for index case of FH by use of FHChip (Vita Genomics, Taiwan and Affymetrix, Santa Clara, CA) which including full coding sequence in 3 most relevant FH genes: LDLR (18 exons including promoters), APOB (exons 26 and 29), PCSK9 (12 exons including promoters), and 64 reported in/del mutations. Multiplex ligation-dependent probe amplification (MRC Holland) study was applied for those without findings in FHChip. Results showed FH mutations in LDLR are highly heterogeneous among Taiwanese and LDLR gene mutations were found in 68% of index cases among severe hypercholesterolemia. Among 66 heterozygous FH (HeFH), 12 complex mutations were noted, with seven of compound heterozygous or single allele double mutations and another five of large genomic duplication or deletion in LDLR genes. Multivariate logistic regression analysis revealed patients with complex mutations had significant higher levels of cholesterol and LDL, higher prevalence of premature CHD, and skin xanthoma than those with single gene point mutation.
　　 In conclusion, our study highlights the importance of early diagnosis and early treatment for patients with FH in Taiwan. Complex mutations in HeFH are not uncommon.