Wu Jun, Province Michael A, Coon Hilary, Hunt Steven C, Eckfeldt John H, Arnett Donna K, Heiss Gerardo, Lewis Cora E, Ellison R Curtis, Rao Dabeeru C, Rice Treva, Kraja Aldi T
Division of Statistical Genomics, Washington University School of Medicine, Campus Box 8506, 4444 Forest Park Boulevard, Saint Louis, MO 63108, USA.
BMC Genet. 2007 Sep 10;8:60. doi: 10.1186/1471-2156-8-60.
Use of anti-hyperlipidemic medications compromises genetic analysis because of altered lipid profiles. We propose an empirical method to adjust lipid levels for medication effects so that the adjusted lipid values substitute the unmedicated lipid values in the genetic analysis.
Published clinical trials were reviewed for HMG-CoA reductase inhibitors and fibric acid derivatives as mono-drug therapy. HMG-CoA reductase inhibitors showed similar effects in African Americans (AA) and non-African Americans (non-AA) for lowering total cholesterol (TC, -50.7 mg/dl), LDL cholesterol (LDL-C, -48.1 mg/dl), and triglycerides (TG, -19.7 mg/dl). Their effect on increasing HDL cholesterol (HDL-C) in AA (+0.4 mg/dl) was lower than in Non-AA (+2.3 mg/dl). The effects of fibric acid derivatives were estimated as -46.1 mg/dl for TC, -40.1 mg/dl for LDL-C, and +5.9 mg/dl for HDL-C in non-AA. The corresponding effects in AA were less extreme (-20.1 mg/dl, -11.4 mg/dl, and +3.1 mg/dl). Similar effect for TG (59.0 mg/dl) was shown in AA and non-AA. The above estimated effects were applied to a multipoint variance components linkage analysis on the lipid levels in 2,403 Whites and 2,214 AA in the HyperGEN study. The familial effects did vary depending on whether the lipids were adjusted for medication use. For example, the heritabilities increased after medication adjustment for TC and LDL-C, but did not change significantly for HDL-C and TG.
Ethnicity-specific medication adjustments using our empirical method can be employed in epidemiological and genetic analysis of lipids.
由于血脂谱改变，使用抗高脂血症药物会影响基因分析。我们提出一种经验方法来调整血脂水平以消除药物影响，从而在基因分析中用调整后的血脂值替代未用药时的血脂值。
我们回顾了已发表的关于HMG - CoA还原酶抑制剂和纤维酸衍生物单药治疗的临床试验。HMG - CoA还原酶抑制剂在非裔美国人（AA）和非非裔美国人（非AA）中降低总胆固醇（TC，-50.7mg/dl）、低密度脂蛋白胆固醇（LDL - C，-48.1mg/dl）和甘油三酯（TG，-19.7mg/dl）的效果相似。它们在AA中升高高密度脂蛋白胆固醇（HDL - C，+0.4mg/dl）的效果低于非AA（+2.3mg/dl）。在非AA中，纤维酸衍生物对TC的影响估计为-46.1mg/dl，对LDL - C的影响为-40.1mg/dl，对HDL - C的影响为+5.9mg/dl。在AA中相应的影响没那么显著（-20.1mg/dl，-11.4mg/dl和+3.1mg/dl）。在AA和非AA中，TG的影响相似（59.0mg/dl）。上述估计的效果应用于HyperGEN研究中对2403名白人和2214名AA血脂水平的多点方差成分连锁分析。家族效应确实因血脂是否针对药物使用进行调整而有所不同。例如，在针对TC和LDL - C进行药物调整后，遗传度增加，但HDL - C和TG的遗传度没有显著变化。
使用我们的经验方法进行种族特异性药物调整可用于血脂的流行病学和基因分析。
