Yang Changsheng, Wang Xiaoping, Ding Hongliu
Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China.
Med Hypotheses. 2008 Sep;71(3):449-52. doi: 10.1016/j.mehy.2008.02.019. Epub 2008 May 8.
The genetic linkage of coronary artery disease is well-established. However, the transmission of this disease is not clearly defined. Although the Mendelian autosomal dominant pattern has been seen in familial hypercholesterolemia and mutant MEF2A induced familiar myocardial infarction, and a multifactorial genetic model has been proposed for non-familial CAD, the gender difference in this disease is not well explained. We hypothesized that CAD is a multifactorial inherited disorder with a sex-influenced trait, which shows an autosomal dominant pattern in men and autosomal recessive transmission in women. This hypothesis is supported by the facts including an age-dependent higher prevalence in men, the autosomal locations of CAD associated genes, the gender difference seen even in familiar CAD, and the potential gene-gene interactions between CAD associated genes on autosomal chromosomes and those found on the X chromosome. Further investigation of genetic components will provide not only the critical information about the etiology of CAD, but also help to clarify the confusion in the use of exogenous female hormones in the prevention and/or the treatment of the disease.
冠状动脉疾病的遗传连锁已得到充分证实。然而，这种疾病的遗传传递方式尚未明确界定。虽然在家族性高胆固醇血症和突变型MEF2A导致的家族性心肌梗死中可见孟德尔常染色体显性模式，并且已针对非家族性冠心病提出了多因素遗传模型，但这种疾病中的性别差异尚未得到很好的解释。我们假设冠心病是一种具有性别影响特征的多因素遗传性疾病，在男性中表现为常染色体显性模式，在女性中表现为常染色体隐性遗传。这一假设得到了以下事实的支持：男性患病率随年龄增长而升高、冠心病相关基因位于常染色体上、即使在家族性冠心病中也存在性别差异，以及常染色体上的冠心病相关基因与X染色体上发现的基因之间存在潜在的基因-基因相互作用。对遗传成分的进一步研究不仅将提供有关冠心病病因的关键信息，还将有助于澄清在预防和/或治疗该疾病中使用外源性女性激素时的困惑。
