Ordovas Jose M
Nutrition and Genomics Laboratory, JM-USDA-Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, USA.
Gend Med. 2007;4 Suppl B:S111-22. doi: 10.1016/s1550-8579(07)80052-0.
Although men and women share most genetic information, they have significantly different disease susceptibilities that go well beyond the expected gender-specific diseases. Sex influences the risk of nearly all common diseases that affect both men and women, including atherosclerosis and diabetes and their preceding risk factors (eg, hyperlipidemia, insulin resistance, and obesity).
The goal of this article was to examine the interplay between genes, gender, and disease susceptibility, and assess it in the context of the added complexity of environmental factors (ie, dietary habits, smoking, alcohol consumption) in the modulation of the balance between health and disease.
Original and review articles published by the author were reexamined for evidence of gene-gender interactions.
Evidence from some key factors in lipid metabolism (apolipoprotein E [APOE])and obesity (perilipin [PLIN]) indicates that the interplay between genes, gender, and environmental factors modulates disease susceptibility. In the Framingham Heart Study, complex interactions have been shown between a promoter polymorphism at the apolipoprotein A1 gene, gender, and dietary poly-unsaturated fatty acid intake that modulate plasma concentrations of high-density lipoprotein cholesterol. Likewise, highly and clinically relevant interactions have been observed between the APOE gene common alleles APOE2 , APOE3, and APOE4 , gender, and smoking that determine cardiovascular disease risk. Most interesting is the gender-dependent association between common polymorphisms at the PLIN locus and obesity risk that has been replicated in several populations around the world.
These data support the idea that gender-specific differences in morbidity and mortality may be mediated in part by genetic factors and by their differential response to the environment. The new knowledge generated by a more careful and complete elucidation of the complex interactions predisposing to common diseases will result in an increased ability to provide successful personalized behavioral recommendations to prevent chronic disorders.
尽管男性和女性共享大部分遗传信息，但他们在疾病易感性方面存在显著差异，远远超出了预期的特定性别疾病范围。性别影响几乎所有影响男性和女性的常见疾病的风险，包括动脉粥样硬化、糖尿病及其前期风险因素（如高脂血症、胰岛素抵抗和肥胖）。
本文的目的是研究基因、性别和疾病易感性之间的相互作用，并在环境因素（即饮食习惯、吸烟、饮酒）增加的复杂性背景下评估其在调节健康与疾病平衡中的作用。
重新审视作者发表的原创文章和综述文章，以寻找基因-性别相互作用的证据。
脂质代谢（载脂蛋白E [APOE]）和肥胖（围脂滴蛋白 [PLIN]）中一些关键因素的证据表明，基因、性别和环境因素之间的相互作用调节了疾病易感性。在弗雷明汉心脏研究中，已表明载脂蛋白A1基因启动子多态性、性别和膳食多不饱和脂肪酸摄入量之间存在复杂的相互作用，这些相互作用调节了高密度脂蛋白胆固醇的血浆浓度。同样，在APOE基因的常见等位基因APOE2、APOE3和APOE4、性别与吸烟之间观察到了高度相关且具有临床意义的相互作用，这些相互作用决定了心血管疾病风险。最有趣的是，PLIN基因座常见多态性与肥胖风险之间的性别依赖性关联已在世界各地的多个群体中得到验证。
这些数据支持这样一种观点，即发病率和死亡率的性别特异性差异可能部分由遗传因素及其对环境的不同反应所介导。对导致常见疾病的复杂相互作用进行更仔细、更全面的阐明所产生的新知识，将提高提供成功的个性化行为建议以预防慢性疾病的能力。
