Van Duijn C M, Clayton D G, Chandra V, Fratiglioni L, Graves A B, Heyman A, Jorm A F, Kokmen E, Kondo K, Mortimer J A, Rocca W A, Shalat S L, Soininen H, Hofman A
Department of Epidemiology and Biostatistics, Erasmus University Medical School, Rotterdam, The Netherlands.
Genet Epidemiol. 1994;11(6):539-51. doi: 10.1002/gepi.1370110609.
To study the interaction among genetic and environmental risk factors, a reanalysis of case-control studies of Alzheimer's disease (AD) was conducted based on the original data of all studies carried out to January 1, 1990. Seven studies were included in the present analysis, comprising a total of 814 AD patients and 894 control subjects. When comparing those with a positive and negative family history of dementia, similar odds ratio were found for late maternal age [1.7; 95% confidence interval (0.6-4.8) vs. 2.0 (1.1-3.5)], head trauma [1.7 (0.7-4.2) vs. 1.9 (1.1-3.2)], and history of depression [2.0 (0.2-19.8) vs. 2.1 (0.8-1.7)]. This suggests a model in which these risk factors increase the risk for AD independent of family history of dementia. Among those with a positive family history of dementia, the odds ratios for family history of Down's syndrome [4.2 (0.9-20.0)] and of Parkinson's disease [3.3 (0.4-28.2)] tended to be higher than among those with a negative family history of dementia [2.6 (0.8-8.5) and 2.4 (0.8-7.0), respectively]. However, for both disorders the difference in odds ratio was not statistically significant. For history of cigarette smoking, there was no association to AD for those with no first degree relatives with dementia and an inverse relation with AD for those with a positive family history. Although in all analyses, family history of dementia remained significantly associated with AD in the absence of other factors, the odds ratio associated with family history of dementia tended to be lower for those with a positive smoking history, particularly for those with two or more affected relatives. These findings suggest that smoking may interact specifically with a genetically determined process.
为研究遗传和环境风险因素之间的相互作用，基于截至1990年1月1日开展的所有研究的原始数据，对阿尔茨海默病（AD）病例对照研究进行了重新分析。本分析纳入了7项研究，共计814例AD患者和894例对照受试者。在比较有痴呆症家族史阳性和阴性的人群时，发现晚育年龄的优势比相似[1.7；95%置信区间（0.6 - 4.8）对比2.0（1.1 - 3.5）]、头部外伤[1.7（0.7 - 4.2）对比1.9（1.1 - 3.2）]以及抑郁症病史[2.0（0.2 - 19.8）对比2.1（0.8 - 1.7）]。这提示了一种模型，即这些风险因素增加AD风险与痴呆症家族史无关。在有痴呆症家族史阳性的人群中，唐氏综合征家族史[4.2（0.9 - 20.0）]和帕金森病家族史[3.3（0.4 - 28.2）]的优势比往往高于有痴呆症家族史阴性的人群[分别为2.6（0.8 - 8.5）和2.4（0.8 - 7.0）]。然而，对于这两种疾病，优势比的差异无统计学意义。对于吸烟史，没有痴呆症一级亲属的人群与AD无关联，而有阳性家族史的人群与AD呈负相关。尽管在所有分析中，在不存在其他因素时痴呆症家族史仍与AD显著相关，但吸烟史阳性的人群与痴呆症家族史相关的优势比往往较低，尤其是有两个或更多患病亲属的人群。这些发现表明吸烟可能与遗传决定的过程发生特异性相互作用。
