期刊论文详细信息
Low-density lipoprotein receptor genotype and response to pravastatin in children with familial hypercholesterolemia - Substudy of an intima-media thickness trial
Article
关键词: CORONARY HEART-DISEASE;    GENE LOCUS;    SIMVASTATIN;    LDL;    CHOLESTEROL;    MUTATIONS;    RISK;    POLYMORPHISM;    THERAPY;   
DOI  :  10.1161/CIRCULATIONAHA.105.565507
来源: SCIE
【 摘 要 】

Background: The lipid-lowering effects of statin therapy show considerable interindividual variation in patients with familial hypercholesterolemia (FH). Whether the type of LDL receptor mutation predicts the response to statin treatment is not yet established. We analyzed the relationship between LDL receptor genotype and response to pravastatin treatment in children with FH using carotid intima-media thickness (IMT) to measure efficacy. Methods and Results: In a randomized, placebo-controlled, double-blind, 2-year trial with pravastatin, 193 children had genetically confirmed FH and were included in the present substudy. At baseline, children with null alleles had higher LDL cholesterol levels (difference, 0.94 +/- 0.19 mmol/ L [SEM]; P < 0.001) and a greater carotid IMT ( difference, 0.019 +/- 0.01 mm; P = 0.02) compared with children with receptor-defective mutations. The decrease in carotid IMT during the trial was not significantly different in children with null alleles and receptor- defective mutations (0.018 +/- 0.012 and 0.012 +/- 0.010 mm; 2-way ANCOVA, P = 0.7). After 2 years of treatment, the children with null alleles continued to have greater carotid IMT than children with receptor- defective mutations ( difference, 0.016 +/- 0.01 mm; P = 0.02). LDL cholesterol lowering tended to be less in carriers of null alleles compared with carriers of receptor-defective mutations (1.30 +/- 0.25 and 1.85 +/- 0.20 mmol/L; 2-way ANCOVA, P = 0.08). Conclusions: In FH children, we found that the null allele genotype was associated with a greater carotid IMT, higher LDL cholesterol levels, and a nonsignificant tendency to attenuated LDL cholesterol lowering compared with receptor- defective mutations. Null alleles identify FH patients at the highest cardiovascular disease risk who may benefit from more aggressive treatment started in childhood.

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