Series J J, Gaffney D, Packard C J, Shepherd J
Area Central Laboratory, Royal United Hospital, Bath, UK.
Clin Chim Acta. 1993 Apr 16;215(1):89-98. doi: 10.1016/0009-8981(93)90252-y.
In this study the frequencies of the genotypes of four restriction fragment length polymorphisms in the apolipoprotein B gene (XbaI, EcoRI, PvuII and MspI) are compared between groups of normolipidaemic and diet resistant hypercholesterolaemic individuals as possible markers for the influence of this gene on plasma cholesterol levels. In the first part of the study genotypes of all four markers were determined in 92 normolipidaemic (mean cholesterol 5.6 + 0.8 mmol/l) and 79 diet resistant hypercholesterolaemic (mean cholesterol 7.8 + 0.7 mmol/l) individuals seen in a local health centre screening programme for coronary heart disease risk factors. No significant difference was seen in the frequencies of the EcoRI and PvuII genotypes between the two groups. There was significant enrichment of both the XbaI X2 (presence of cutting site) allelic frequency and of the MspI M1M2 (M2 absence of cutting site, rarer allele) genotype frequency in the hypercholesterolaemic group. In the second part of the study an independent larger group of individuals, seen in a multicentre screening programme across the city of Glasgow, were genotyped for the two potentially significant polymorphic sites (XbaI and MspI). From this second screening programme 188 age matched normolipidaemic males (mean cholesterol 5.0 +/- 0.8 mmol/l) were compared with 186 males who were still hypercholesterolaemic (mean 8.2 +/- 0.6 mmol/l) after three months dietary intervention. The hypercholesterolaemic individuals in this second study did not show a significant enrichment of the XbaI X2 allele but again showed a highly significant enrichment of the MspI M1M2 genotype. This genetic effect may relate directly to the charge change from arginine to glutamine at amino acid 3611 caused by the MspI mutation or to an as yet unknown functionally significant mutation in linkage disequilibrium with this site.
在本研究中，对载脂蛋白B基因中四种限制性片段长度多态性（XbaI、EcoRI、PvuII和MspI）的基因型频率在血脂正常和饮食抵抗性高胆固醇血症个体组之间进行了比较，将其作为该基因对血浆胆固醇水平影响的可能标志物。在研究的第一部分，在当地健康中心冠心病危险因素筛查项目中，对92名血脂正常者（平均胆固醇5.6±0.8 mmol/L）和79名饮食抵抗性高胆固醇血症患者（平均胆固醇7.8±0.7 mmol/L）测定了所有四种标志物的基因型。两组之间EcoRI和PvuII基因型频率无显著差异。在高胆固醇血症组中，XbaI X2（存在切割位点）等位基因频率和MspI M1M2（M2不存在切割位点，较罕见等位基因）基因型频率均有显著富集。在研究的第二部分，对在格拉斯哥市多中心筛查项目中见到的一组独立的更大样本个体，对两个潜在显著的多态性位点（XbaI和MspI）进行基因分型。从这第二个筛查项目中，将188名年龄匹配的血脂正常男性（平均胆固醇5.0±0.8 mmol/L）与186名在三个月饮食干预后仍为高胆固醇血症的男性（平均8.2±0.6 mmol/L）进行比较。第二项研究中的高胆固醇血症个体未显示XbaI X2等位基因有显著富集，但再次显示MspI M1M2基因型有高度显著富集。这种遗传效应可能直接与MspI突变导致的第3611位氨基酸从精氨酸到谷氨酰胺的电荷变化有关，或者与与此位点处于连锁不平衡状态的一个尚未知晓的功能上显著的突变有关。
