Leppert M, Breslow J L, Wu L, Hasstedt S, O'Connell P, Lathrop M, Williams R R, White R, Lalouel J M
Howard Hughes Medical Institute, University of Utah Medical Center, Salt Lake City 84132.
J Clin Invest. 1988 Sep;82(3):847-51. doi: 10.1172/JCI113688.
Heterozygous hypobetalipoproteinemia is characterized by reduced plasma concentrations of LDL cholesterol, total triglycerides, and apo B to less than 50% of normal values. The molecular basis of this disorder remains unknown. The phenotype cosegregates with a DNA haplotype of the apo B gene in an Idaho pedigree, with a maximum decimal logarithm of the ratio (LOD) score of 7.56 at a recombination rate of zero. Individuals carrying this haplotype had total cholesterol levels of 96 mg/dl, LDL cholesterol levels of 37 mg/dl, triglycerides levels of 51 mg/dl, and apo B levels of 38 mg/dl. This study strongly suggests that apo B mutations underlie hypobetalipoproteinemia, and demonstrates the power of the candidate gene approach in linkage analysis for unraveling genetic determinants in metabolic disorders of undefined etiology.
杂合子低β脂蛋白血症的特征是血浆中低密度脂蛋白胆固醇、总甘油三酯和载脂蛋白B的浓度降低至正常水平的50%以下。这种疾病的分子基础仍然未知。在爱达荷州的一个家系中，该表型与载脂蛋白B基因的一个DNA单倍型共分离，在重组率为零时，最大对数优势比（LOD）分数为7.56。携带这种单倍型的个体总胆固醇水平为96mg/dl，低密度脂蛋白胆固醇水平为37mg/dl，甘油三酯水平为51mg/dl，载脂蛋白B水平为38mg/dl。这项研究有力地表明，载脂蛋白B突变是低β脂蛋白血症的基础，并证明了候选基因方法在连锁分析中对于揭示病因不明的代谢紊乱的遗传决定因素的作用。
