标题：Electrophoretic screening for genetic variation in apolipoprotein C-III: identification of a novel apoC-III variant, apoC-III(Asp45-->Asn), in a Turkish patient.
出版社：American Society for Biochemistry and Molecular Biology
摘要：Screening of 6,840 plasma samples by isoelectric focusing (IEF) led to the identification of a novel apolipoprotein C-III variant. The underlying molecular defect was established by sequencing of exons 3 and 4 of the apoC-III gene subsequent to their amplification by the polymerase chain reaction (PCR). A G-->A transition in the first nucleotide of codon 45 results in a replacement of aspartic acid by asparagine. ApoC-III(Asp45-->Asn) was detected in a Turkish patient who previously had undergone coronary bypass surgery. Family studies identified two of the three children of the index patient as heterozygous variant carriers. The family was too small to demonstrate a significant effect of the variant on lipid metabolism. However, as judged by two-dimensional immunoelectrophoresis as well as IEF and subsequent scanning densitometry, the concentrations of the variant allele products were increased twofold in very low density lipoproteins (VLDL) and slightly decreased both in low density lipoproteins (LDL) and in high density lipoproteins (HDL) relative to the concentrations of the normal allele products. The disproportional distribution of the variant apoC-III isoproteins may indicate differences in the metabolism of variant and normal apoC-III. We conclude that genetically determined structural variants of apoC-III with changes in complete net charges are very rare and, hence, do not significantly contribute to the formation of dyslipidemia in the German population. Although heterozygosity for apoC-III(Asp45-->Asn) is not associated with severe dyslipidemia, the disproportional distribution of the allele products among plasma lipoproteins indirectly indicates some impact on lipoprotein metabolism.
