Carmena R, Roederer G, Mailloux H, Lussier-Cacan S, Davignon J
Hospital Clinico Universitario, Endocrine Service, Valencia, Spain.
Metabolism. 1993 Jul;42(7):895-901. doi: 10.1016/0026-0495(93)90066-w.
In a retrospective study, we examined the influence of apolipoprotein (apo) E polymorphism and gender on the response to treatment with 80 mg/d lovastatin in a homogeneous population of patients with familial hypercholesterolemia (FH), most of whom were carriers of the 10-kb deletion of the low-density lipoprotein (LDL) receptor gene. Apo E phenotype distribution among the 189 FH patients was not different from that of a normal population sample. The total and LDL cholesterol (LDL-C) response to lovastatin in the overall group (men and women) was significantly lower in the E4 subset compared with E2 and E3 subsets. This finding is in agreement with trends observed in previous reports. On the other hand, the response of LDL-C to lovastatin was significantly lower in E4 men than in E4 women, whereas the high-density lipoprotein cholesterol (HDL-C) concentration in the E4 group increased significantly more in men than in women, suggesting a role of gender in modulating the response to lovastatin. Hence, apo E polymorphism influenced LDL-C (and HDL-C) response to lovastatin in men, but not in women, revealing the existence of a gene-by-gender interaction. These findings were independent of the nature of the LDL receptor defect. We conclude that male FH patients carrying the epsilon 4 allele respond less efficiently to lovastatin than men carrying the epsilon 3 or epsilon 2 allele or women of any apo E phenotype with respect to decreasing total cholesterol and LDL-C levels, but respond more efficiently with respect to increasing HDL-C levels. The full practical implication of these findings remains to be explored.
在一项回顾性研究中，我们在一组均一的家族性高胆固醇血症（FH）患者中，研究了载脂蛋白（apo）E基因多态性和性别对每日80 mg洛伐他汀治疗反应的影响。这些患者大多数是低密度脂蛋白（LDL）受体基因10 kb缺失的携带者。189例FH患者的apo E表型分布与正常人群样本无差异。在总体组（男性和女性）中，与E2和E3亚组相比，E4亚组对洛伐他汀的总胆固醇和低密度脂蛋白胆固醇（LDL-C）反应显著降低。这一发现与先前报道中观察到的趋势一致。另一方面，E4男性对洛伐他汀的LDL-C反应显著低于E4女性，而E4组中男性的高密度脂蛋白胆固醇（HDL-C）浓度升高显著高于女性，提示性别在调节对洛伐他汀的反应中起作用。因此，apo E基因多态性影响男性对洛伐他汀的LDL-C（和HDL-C）反应，但不影响女性，揭示了基因-性别相互作用的存在。这些发现与LDL受体缺陷的性质无关。我们得出结论，携带ε4等位基因的男性FH患者在降低总胆固醇和LDL-C水平方面，对洛伐他汀的反应不如携带ε3或ε2等位基因的男性或任何apo E表型的女性有效，但在升高HDL-C水平方面反应更有效。这些发现的全部实际意义仍有待探索。
