Joossens J V
Department of Epidemiology, K.U. Leuven, Belgium.
Acta Cardiol Suppl. 1988;29:63-83.
Hypercholesterolemia is the result of an imbalance between two basic cholesterol homeostatic mechanisms. One is related to intercellular and the other to extracellular cholesterol homeostasis. The human organism gives always absolute priority to the intracellular homeostasis. The naturally occurring balance between both systems can be disturbed: 1) By genetic factors, one of them located on chromosome 19 and governing the number of LDL-receptors on the cell membrane (liver, arterial wall, adrenals, fibroblasts, etc.). Total genetic absence of malfunction of LDL-receptors is seen in homozygote familial hypercholesterolemia, with ischemic heart disease between ages 2 and 25. Less harmful situations arise from heterozygote familial hypercholesterolemia and from other genetic defects (among them those located at the gene of apo E on chromosome 19 and of apo AI on chromosome 11). 2) By nutritional factors decreasing or totally blocking the number of active LDL-receptors. This has been demonstrated in the rabbit, hamster, dog, baboon and humans. Overloading the organism with dietary cholesterol and saturated fat is one extremely common factor in western societies. Certain fats (omega-6 and omega-3 polyunsaturated, and oleic acid) may be beneficial. Other factors are generally of lesser importance. 3) By a combination in different proportions of 1) and 2). Severe dietary overloading with cholesterol and saturated fat in the rabbit results in early atherosclerotic lesions resembling almost totally those produced by the genetic absence of LDL-receptors (Watanabe rabbit). In humans from western countries the serum LDL-level is more related to environmental factors, whereas the HDL-level is more related to genetic factors. Age is an important factor integrating the effects of genetics and environmental deviations. The influence of sex is also important. Serum cholesterol in western countries is increasing markedly with age, but this growth of serum cholesterol with age is totally different between sexes. Serum cholesterol is on the average only equal in both sexes at ages 3, 10, 25 and 50. It is higher in males between ages 25 and 50 and higher in females between ages 3 to 10, 10 to 25 and above 50 years. In general females are less susceptible to higher cholesterolemia than males except at very old ages (above 80-85 years). Together with other observations of sex linked differences this points to the influence of a sex linked chromosome, most probably the X-chromosome. The susceptibility of females in a given population decreases with decreasing levels of infectious diseases, the opposite is true for males.(ABSTRACT TRUNCATED AT 400 WORDS)
高胆固醇血症是两种基本胆固醇稳态机制失衡的结果。一种与细胞内胆固醇稳态有关，另一种与细胞外胆固醇稳态有关。人类机体总是绝对优先考虑细胞内稳态。这两个系统之间自然存在的平衡可能会受到干扰：1）遗传因素，其中之一位于19号染色体上，控制细胞膜（肝脏、动脉壁、肾上腺、成纤维细胞等）上低密度脂蛋白受体的数量。纯合子家族性高胆固醇血症患者存在低密度脂蛋白受体完全缺失或功能异常的情况，2至25岁之间易患缺血性心脏病。杂合子家族性高胆固醇血症以及其他遗传缺陷（包括位于19号染色体上的载脂蛋白E基因和11号染色体上的载脂蛋白AI基因的缺陷）则危害较小。2）营养因素导致活性低密度脂蛋白受体数量减少或完全阻断。这已在兔子、仓鼠、狗、狒狒和人类身上得到证实。在西方社会，饮食中胆固醇和饱和脂肪摄入过多是一个极其常见的因素。某些脂肪（ω-6和ω-3多不饱和脂肪酸以及油酸）可能有益。其他因素一般不太重要。3）1）和2）以不同比例组合。兔子饮食中严重过量摄入胆固醇和饱和脂肪会导致早期动脉粥样硬化病变，几乎完全类似于因低密度脂蛋白受体基因缺失产生的病变（渡边兔）。在西方国家，人类血清低密度脂蛋白水平与环境因素关系更大，而高密度脂蛋白水平与遗传因素关系更大。年龄是综合遗传和环境偏差影响的重要因素。性别影响也很重要。西方国家血清胆固醇水平随年龄显著升高，但血清胆固醇随年龄的增长在两性之间完全不同。血清胆固醇平均仅在3岁、10岁、25岁和50岁时在两性中相等。25至50岁男性的血清胆固醇较高，3至10岁、10至25岁以及50岁以上女性的血清胆固醇较高。一般来说，除了非常年老（80 - 85岁以上）外，女性比男性更不易患高胆固醇血症。连同其他关于性别相关差异的观察结果，这表明存在性连锁染色体的影响，很可能是X染色体。特定人群中女性的易感性随传染病水平降低而降低，男性则相反。（摘要截选至400字）
