在对 98529 名丹麦成年人进行的观察性或孟德尔随机化分析中，牛奶摄入量与缺血性心脏病无关。
Milk intake is not associated with ischaemic heart disease in observational or Mendelian randomization analyses in 98,529 Danish adults.
机构信息
Department of Clinical Biochemistry, Naestved Hospital, Denmark, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark, Department of Clinical Biochemistry and the Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen, Denmark, Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen, Denmark, Department of Research, Nykoebing Falster Hospital, Nykoebing Falster, Denmark and Department of Laboratory Medicine, Boston Children's Hospital, Boston, MA, USA Department of Clinical Biochemistry, Naestved Hospital, Denmark, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark, Department of Clinical Biochemistry and the Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen, Denmark, Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen, Denmark, Department of Research, Nykoebing Falster Hospital, Nykoebing Falster, Denmark and Department of Laboratory Medicine, Boston Children's Hospital, Boston, MA, USA.
Department of Clinical Biochemistry, Naestved Hospital, Denmark, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark, Department of Clinical Biochemistry and the Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen, Denmark, Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen, Denmark, Department of Research, Nykoebing Falster Hospital, Nykoebing Falster, Denmark and Department of Laboratory Medicine, Boston Children's Hospital, Boston, MA, USA Department of Clinical Biochemistry, Naestved Hospital, Denmark, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark, Department of Clinical Biochemistry and the Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen, Denmark, Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen, Denmark, Department of Research, Nykoebing Falster Hospital, Nykoebing Falster, Denmark and Department of Laboratory Medicine, Boston Children's Hospital, Boston, MA, USA Department of Clinical Biochemistry, Naestved Hospital, Denmark, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark, Department of Clinical Biochemistry and the Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen, Denmark, Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen, Denmark, Department of Research, Nykoebing Falster Hospital, Nykoebing Falster, Denmark and Department of Laboratory Medicine, Boston Children's Hospital, Boston, MA, USA.
出版信息
Int J Epidemiol. 2015 Apr;44(2):587-603. doi: 10.1093/ije/dyv109.
BACKGROUND
Observationally, reports on the association between milk intake and risk of ischaemic heart disease (IHD) and myocardial infarction (MI) have produced conflicting results; and no previous large-scale study using the lactase persistent/non-persistent LCT-13910 C/T genotype as a largely unconfounded proxy for milk intake free of reverse causation has been conducted. We tested the hypothesis that milk intake observationally and genetically through the LCT-13910 C/T genotype is associated with risk of IHD and MI in a Mendelian randomization design.
METHODS
We included 98,529 White individuals of Danish descent, aged 20-100 years, from three studies of the general population. Information on IHD (N = 10,372) and MI (N = 4188) were obtained from national Danish registries. First, we investigated observational associations between milk intake and incident IHD and MI. Second, we confirmed the association between the rs4988235 genetic variant LCT-13910 C/T, associated with lactase persistence/non-persistence, and milk intake. Finally, we tested whether LCT-13910 C/T genotype was associated with risk of IHD and MI as well as with cardiovascular risk factors.
RESULTS
During a mean follow-up time of 5.4 years, the observational hazard ratio for a 1 glass/week higher milk intake was 1.00 [95% confidence interval (CI): 1.00,1.01] for both IHD and MI. Median milk intake was 3 glasses/week (interquartile range: 0-7) in lactase CC non-persistent individuals compared with 5 glasses/week (0-10) in lactase TC/TT persistent individuals (P = 3*10(-60)). In the dominant genetic model comparing lactase TC/TT persistent individuals with lactase CC non-persistent individuals, the odds ratio was 1.00 (0.92,1.09) for IHD and 0.96 (0.84,1.09) for MI. Finally, in the dominant genetic model genotype was not associated convincingly with plasma levels of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides or glucose, nor with blood pressure.
CONCLUSION
Milk intake was not associated with risk of IHD or MI, observationally or genetically.
背景
观察性研究报告表明，牛奶摄入与缺血性心脏病（IHD）和心肌梗死（MI）风险之间存在关联，但此前尚无使用乳糖酶持续/非持续 LCT-13910 C/T 基因型作为不受反向因果关系影响的牛奶摄入的大型研究。我们通过孟德尔随机设计检验了牛奶摄入和通过 LCT-13910 C/T 基因型遗传与 IHD 和 MI 风险相关的假设。
方法
我们纳入了 98529 名丹麦裔白种人，年龄在 20-100 岁之间，来自三项一般人群研究。IHD（N=10372）和 MI（N=4188）的信息从丹麦国家登记处获得。首先，我们调查了牛奶摄入与 IHD 和 MI 发病之间的观察性关联。其次，我们确认了与乳糖酶持续/非持续相关的 rs4988235 基因变异 LCT-13910 C/T 与牛奶摄入之间的关联。最后，我们测试了 LCT-13910 C/T 基因型是否与 IHD 和 MI 风险以及心血管风险因素相关。
结果
在平均 5.4 年的随访期间，每周多喝 1 杯牛奶的观察性危害比为 1.00[95%置信区间（CI）：1.00，1.01]，用于 IHD 和 MI。乳糖酶 CC 非持续个体的中位牛奶摄入量为 3 杯/周（四分位距：0-7），而乳糖酶 TC/TT 持续个体为 5 杯/周（0-10）（P=3*10(-60)）。在比较乳糖酶 TC/TT 持续个体与乳糖酶 CC 非持续个体的显性遗传模型中，IHD 的比值比为 1.00（0.92，1.09），MI 为 0.96（0.84，1.09）。最后，在显性遗传模型中，基因型与总胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、甘油三酯或血糖的血浆水平以及血压均无明显关联。
结论
观察或遗传上，牛奶摄入与 IHD 或 MI 风险无关。
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