Identification and haplotype analysis of apolipoprotein B-100 Arg₃₅₀₀Trp mutation in hyperlipidemic Chinese

¹ Department of Internal Medicine, Wei Gong Memorial Hospital, Tou Fen, Miaoli, Taiwan 351, Republic of China.

² Division of Cardiology, Department of Medicine, Veterans General Hospital-Taipei, National Yang-Ming University, School of Medicine, Taipei, Taiwan 112, Republic of China.

³ Department of Biology, National Taiwan Normal University, Taipei, Taiwan 117, Republic of China.
^a Author for correspondence. Fax 886-2-29312904; e-mail t43019{at}cc.ntnu.edu.tw.

DNA screening for apolipoprotein (apo) B-100 mutations was performed in hyperlipidemic Chinese. The apo B-100 gene segment surrounding previously identified familial defective apo B-100 (FDB) mutations was amplified by PCR and subjected to single-strand conformation polymorphism (SSCP) analysis. One subject's aberrant SSCP band was cloned and sequenced to study the molecular lesions. A recurrent Arg_CGG-to-Trp_TGG mutation (R3500W) in the codon 3500 of the apo B-100 gene was identified. The C-to-T transition creates a NlaIII site and permits rapid restriction analysis of the mutation. A total of 373 hyperlipidemic patients and 309 controls were screened for R3500W. Nine unrelated subjects were shown to be heterozygous for the mutation, and no R3500W carriers were found in the control group (P = 0.004). Six polymorphic markers, including five restriction fragment length polymorphisms and one hypervariable repeat region, were used for haplotype analysis on the mutant allele. In two families, the R3500W mutation could be unambiguously assigned to a unique haplotype XbaI-/MaeI+/MspI+/EcoRI+/Eco57I+/34 3'HVR repeats; in the other seven unrelated heterozygotes, this finding was consistent when an unequivocal haplotype was deduced. The results suggest that all R3500W alleles are identical by descent in our population. The fact that the same mutant allele was identified in other Asians with FDB indicates a common Asian origin for the R3500W mutations.

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