Low-density lipoprotein receptor gene mutations in a Southeast Asian population with familial hypercholesterolemia

• Published in: Clinical genetics 2000-08, Vol.58 (2), p.98-105
• Main Authors: Khoo, Kl, Van Acker, P, Defesche, Jc, Tan, H, Van De Kerkhof, L, Heijnen-van Eijk, Sj, Kastelein, Jjp, Deslypere, Jp
• Format: Article
• Language: English
• Subjects: Adult; Aged; Apolipoproteins B - genetics; Asia, Southeastern - epidemiology; Biological and medical sciences; DGGE; Disorders of blood lipids. Hyperlipoproteinemia; DNA Primers - chemistry; Electrophoresis, Agar Gel; familial hypercholesterolemia; Female; FH3 gene; Genotype; genotype-phenotype relation; Humans; Hyperlipoproteinemia Type II - ethnology; Hyperlipoproteinemia Type II - genetics; Lipoproteins - analysis; low-density lipoprotein receptor; Male; Medical sciences; Metabolic diseases; Middle Aged; Mutation - genetics; Phenotype; Polymerase Chain Reaction; premature coronary heart disease; Receptors, LDL - genetics; Sequence Analysis, DNA; Tropical medicine
• ISSN: 0009-9163; 1399-0004
• DOI: 10.1034/j.1399-0004.2000.580202.x

The aim of this study was to detect mutations in the genes coding for the low‐density lipoprotein receptor and apolipoprotein B in patients of Southeast Asian origin with clinically diagnosed familial hypercholesterolemia (FH) and to relate these findings with the observed lower incidence of coronary heart disease in this part of the world. 
A total of 86 unrelated patients with FH were selected on clinical grounds, and complete DNA analysis of the low‐density lipoprotein (LDL)‐receptor and apolipoprotein B (apoB) genes by DGGE and DNA‐sequencing was performed. In the majority (73%) of the cohort studied, no mutations could be detected, even after extensive analysis of the LDL‐receptor and apoB genes. However, the 22 patients with a mutation had significantly more xanthomas and a higher incidence of coronary heart disease and levels of low‐density lipoproteins were also significantly different. There was no correlation between the type of the mutation and lipoprotein levels or clinical signs of atherosclerosis. 
The fact that the majority of the FH patients studied had no detectable mutation and that this group had a significant milder phenotype, suggests the presence of a third gene in the Southeast Asian population, predominantly leading to a disorder resembling a milder form of FH. A similar, but less frequent, trait has recently been described in a number of European families