title: Familial defective apolipoprotein B-100: detection and haplotype analysis of the Arg(3500)-->Gln mutation in hyperlipidemic Chinese.
abstract: Familial defective apolipoprotein (apo) B-100 (FDB) is caused by R3500Q mutation of the apo B gene resulting in decreased binding of LDL to the LDL receptor. Two other apo B mutations, R3500W and R3531C, affecting binding are known to date. We screened the apo B gene segment around codon 3500 by heteroduplex analysis and single strand conformation polymorphism (SSCP) analysis in a total of 373 hyperlipidemic individuals. Two single-base mutations were detected and confirmed by DNA sequencing. One mutation, ACA(3528)-->ACG change, resulted in degenerate codon with no amino acid substitution. The other mutation, CGG(3500)-->CAG mutation, resulted in an Arg(3500)-->Gln substitution (R3500Q). The prevalence of heterozygote in this selected population was 0.3% (95% confidence interval, 0.01-1.5%) for the R3500Q mutation, and 2.4% (95% confidence interval, 1.1-4.5%) for the previously described R3500W mutation. The results suggest that the R3500Q mutation is not a significant factor contributing to moderate hypercholesterolemia in Chinese (P=0.027). Family studies of the R3500Q carrier revealed a further two individuals heterozygous for the mutation, both of whom were hypercholesterolemic. Analysis of the R3500Q allele using six diallelic markers and the 3'HVR marker revealed a haplotype which was the same as that reported in a Chinese American but differed from that reported in a Chinese Canadian. Our data support limited multiple recurrent origins for R3500Q in Chinese population.
authors.affiliation: Department of Biology, National Taiwan Normal University, 88 Ting-Chou Road, Section 4, 117, Taipei, Taiwan, ROC.
authors.forename: Y N
authors.initials: YN
authors.lastname: Teng
authors.forename: J P
authors.initials: JP
authors.lastname: Pan
authors.forename: S C
authors.initials: SC
authors.lastname: Chou
authors.forename: D Y
authors.initials: DY
authors.lastname: Tai
authors.forename: G J
authors.initials: GJ
authors.lastname: Lee-Chen
mesh_terms: D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002681:China; D005260:Female; D005787:Gene Frequency; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D006949:Hyperlipidemias / Q000235:genetics*; D007223:Infant; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational
chemical_list: D053299:Apolipoprotein B-100; D001055:Apolipoproteins B