Genest J J, Ordovas J M, McNamara J R, Robbins A M, Meade T, Cohn S D, Salem D N, Wilson P W, Masharani U, Frossard P M
Lipid Metabolism Laboratory, USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111.
Atherosclerosis. 1990 May;82(1-2):7-17. doi: 10.1016/0021-9150(90)90138-9.
Elevated plasma levels of low density cholesterol and their major apolipoprotein (apo B) are associated with an increased risk of coronary artery disease (CAD). We have examined allele frequencies of restriction fragment length polymorphisms (RFLP) of the apo B gene in 111 male Caucasians with premature CAD (mean age 49 +/- 7 years) and in 122 elderly Caucasian males (mean age, 73 +/- 5 years), free of clinical cardiovascular disease. The rare allele (R1) of the EcoR1 RFLP in exon 29, resulting in an amino acid change (Glu----Lys4154) was seen more frequently in CAD than in controls (0.270 vs 0.207, P less than 0.05). The R1 RFLP and the MspI insertion polymorphisms (MI) within the 3' hypervariable region (HVR) were observed together in 87% and are likely in linkage disequilibrium. The MI RFLP were slightly more frequent in CAD than control (0.239 vs. 0.211, P = 0.08). A second MspI RFLP in exon 26 results in an amino acid change (Arg----Glu3611); the rare allele M2 was seen more frequently in patients than in controls (0.150 vs. 0.057, P less than 0.005). No significant differences in allele frequencies were observed for the Xba1 RFLP in exon 26 (0.500 vs. 0.529, P = ns) or for the PvuII RFLP near the 5' end (P2) (0.105 vs. 0.088, P = ns). No statistically significant differences in lipid, lipoprotein cholesterol or apolipoproteins A-I and B were observed in patients or in controls. Two of the RFLPs examined (R1 and M2) result in changes in amino acid sequence and their allele frequencies are increased in CAD cases when compared with controls. Genetic variability within the apo B gene may thus contribute to cardiovascular risk. The physiological effects of individual mutations within apo B remain to be determined. It is unlikely, however that the single site polymorphisms examined in this study, will impart further information about CAD risk than conventional lipid parameters.
血浆中低密度胆固醇及其主要载脂蛋白（载脂蛋白B）水平升高与冠状动脉疾病（CAD）风险增加相关。我们检测了111名患有早发性CAD的白人男性（平均年龄49±7岁）和122名无临床心血管疾病的老年白人男性（平均年龄73±5岁）中载脂蛋白B基因限制性片段长度多态性（RFLP）的等位基因频率。第29外显子中EcoR1 RFLP的罕见等位基因（R1）导致氨基酸改变（Glu→Lys4154），在CAD患者中比对照组更常见（0.270对0.207，P<0.05）。R1 RFLP与3'高变区（HVR）内的MspI插入多态性（MI）在87%的情况下共同出现，可能处于连锁不平衡状态。MI RFLP在CAD患者中比对照组略为常见（0.239对0.211，P = 0.08）。第26外显子中的第二个MspI RFLP导致氨基酸改变（Arg→Glu3611）；罕见等位基因M2在患者中比对照组更常见（0.150对0.057，P<0.005）。第26外显子中Xba1 RFLP的等位基因频率（0.500对0.529，P =无显著性差异）或5'端附近的PvuII RFLP（P2）（0.105对0.088，P =无显著性差异）未观察到显著差异。患者或对照组在血脂、脂蛋白胆固醇或载脂蛋白A-I和B方面未观察到统计学上的显著差异。所检测的两个RFLP（R1和M2）导致氨基酸序列改变，与对照组相比，其等位基因频率在CAD病例中增加。因此，载脂蛋白B基因内的遗传变异性可能导致心血管风险。载脂蛋白B内个别突变的生理效应仍有待确定。然而，本研究中检测的单一位点多态性不太可能比传统血脂参数提供更多关于CAD风险的信息。
