An investigation of the effects of lipid-lowering medications: genome-wide linkage analysis of lipids in the HyperGEN study
An investigation of the effects of lipid-lowering medications: genome-wide linkage analysis of lipids in the HyperGEN study
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DOI：
10.1186/1471-2156-8-60
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发表时间：
2007-09-10
期刊：
影响因子：
2.9
通讯作者：
Kraja, Aldi T.
中科院分区：
文献类型：
--
作者：
Wu, Jun;Province, Michael A.;Kraja, Aldi T.
背景：抗高血压药物的使用会影响基因分析，因为血脂谱会改变。我们提出了一个经验的方法来调整血脂水平的药物作用，使调整后的血脂值取代未用药的血脂值在genetic analysis.Results：发表的临床试验进行了审查HMG-CoA还原酶抑制剂和纤维酸衍生物作为单药治疗。HMG-CoA还原酶抑制剂在非洲裔美国人（AA）和非非洲裔美国人（非AA）中显示出降低总胆固醇（TC，-50.7 mg/dl）、LDL胆固醇（LDL-C，-48.1 mg/dl）和甘油三酯（TG，-19.7 mg/dl）的相似作用。它们对AA（+0.4 mg/dl）中HDL胆固醇（HDL-C）升高的作用低于非AA（+2.3 mg/dl）。在非AA患者中，纤维酸衍生物对TC的影响估计为-46.1 mg/dl，对LDL-C的影响估计为-40.1 mg/dl，对HDL-C的影响估计为+5.9 mg/dl。AA中的相应效应不太极端（-20.1 mg/dl、-11.4 mg/dl和+3.1 mg/dl）。在AA和非AA中显示了对TG（59.0 mg/dl）的类似作用。将上述估计效应应用于HyperGEN研究中2，403例白人和2，214例AA的脂质水平的多点方差分量连锁分析。家族效应确实因血脂是否因药物使用而调整而异。例如，药物调整后TC和LDL-C的遗传性增加，但HDL-C和TG没有显着变化。结论：种族特定的药物调整，使用我们的经验方法可以在流行病学和遗传分析血脂。
Background: 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.Results: 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.Conclusion: Ethnicity-specific medication adjustments using our empirical method can be employed in epidemiological and genetic analysis of lipids.