title: Denaturing gradient-gel electrophoresis screening of familial defective apolipoprotein B-100 in a mixed Asian cohort: two cases of arginine3500-->tryptophan mutation associated with a unique haplotype.
abstract: The Arg-to-Trp substitution at codon 3500 in the apolipoprotein (apo) B-100 gene is established as a cause of familial defective apo B-100 (FDB), a functional mutation, resulting in reduced LDL receptor binding and manifest hypercholesterolemia. In a search for similar mutations in 163 Malaysians, we screened the putative receptor-binding region (codons 3456-3553) of the apo B-100 gene by PCR amplification and denaturing gradient-gel electrophoresis. Four single-base mutations were detected and confirmed by DNA sequencing. Two females, a Chinese and a Malay, had the same CGG3500-->TGG mutation, resulting in an Arg3500-to-Trp substitution. This is the second published report of such an independent mutation involving the same codon as the established Arg3500-to-Gln mutation. The two other mutations detected, CTT3517-->CTG and GCC3527-->GCT, resulted in degenerate codons with no amino acid substitutions. All four mutations were associated with a unique apo B haplotype, different from those found in Caucasian FDB patients but concurring with that previously reported for two other Asians with FDB.
authors.affiliation: Department of Pathology, National University of Singapore, Singapore.
authors.forename: M L
authors.initials: ML
authors.lastname: Choong
authors.forename: E S
authors.initials: ES
authors.lastname: Koay
authors.forename: K L
authors.initials: KL
authors.lastname: Khoo
authors.forename: M C
authors.initials: MC
authors.lastname: Khaw
authors.forename: S K
authors.initials: SK
authors.lastname: Sethi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B / Q000032:analysis* / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics; D001120:Arginine / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003062:Codon; D015331:Cohort Studies; D004252:DNA Mutational Analysis / Q000379:methods; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods*; D005006:Ethnicity; D005091:Exons; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009691:Nucleic Acid Denaturation; D011110:Polymorphism, Genetic; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism; D014364:Tryptophan / Q000235:genetics*
chemical_list: D053299:Apolipoprotein B-100; D001055:Apolipoproteins B; D001057:Apolipoproteins E; D008078:Cholesterol, LDL; D003062:Codon; D011973:Receptors, LDL; D014364:Tryptophan; D001120:Arginine; D002784:Cholesterol