J Med Assoc Thai 2001; 84 (12):690

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Homozygous DNA Variants in Exon 9 of the LDL Receptor Gene in a Thai Patient with Primary Hypercholesterolemia Phenotype
Pongrapeeporn K Mail, Thepsuriyanon P , Yamwong P , Leowattana W , Nuchpramool W , OngAjyooth S , Sribhen K

Mutation in low density lipoprotein (LDL) receptor gene causes an inherited primary
hypercholesterolemia namely familial hypercholesterolemia (FH). In this study, 46 Thai patients
with primary hypercholesterolemia were screened for mutations in exon 9 of the LDL receptor
gene by polymerase chain reaction -restriction fragment length polymorphism (PCR -RFLP). The
analysed fragment was 224 bp in length. According to the published eDNA sequence, exon 9 of
the LDL receptor gene contains several hypermutable CpG dinucleotides. Three of these sites are
Hpa II recognition sites. PCR product of exon 9 obtained from amplification of wild-type DNA
sample would yield four fragments after Hpa II digestion. The expected sizes of these restriction
fragments were 15, 30, 40 and 139 bp. All normocholesterolemic subjects (n
33) showed normal
RFLP. However, in one patient (72 year old female), abnormal RFLP from Hpa II digestion of the
amplified exon 9 was observed, i.e., a fragment of 70 bp and another one smaller than 139 bp.
Such RFLP reflects that exon 9 of both alleles of the LDL receptor gene in this patient lost one
and gained one Hpa II site. It is interesting that this patient, eventhough harbouring two mutations
on both alleles of the LDL receptor gene (presumably homozygous genotype of FH), apparently
lipid levels of heterozygous phenotype of FH without symptoms of coronary artery
disease. It has yet to be proved whether these genetic variations are disease-related mutations or
presumably common DNA polymorphisms.
Key word : Hypercholesterolemia, CpG Dinucleotides, Gene Mutations, PCR-RFLP, LDL Receptor

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