Marder Karen, Levy Gilberto, Louis Elan D, Mejia-Santana Helen, Cote Lucien, Andrews Howard, Harris Juliette, Waters Cheryl, Ford Blair, Frucht Steven, Fahn Stanley, Ottman Ruth
Department of Neurology, Columbia University, New York, NY, USA.
Ann Neurol. 2003 Oct;54(4):507-13. doi: 10.1002/ana.10711.
The role of heredity in early- versus late-onset Parkinson's disease (PD) is controversial. We estimated the degree of increased risk of PD in first-degree relatives of 221 PD probands with age of onset 50 years or younger and 266 PD probands with age of onset older than 50 years compared with the first-degree relatives of 409 control probands. Risk of PD was similar among first-degree relatives of early-onset PD probands (risk ratio [RR], 2.9; 95% confidence interval [CI], 1.6-5.0; p = 0.0002) and late-onset PD probands (RR, 2.7; 95% CI, 1.6-4.4; p = 0.0002) when each was compared with first-degree relatives of controls. However, siblings of early-onset PD probands were at markedly increased risk of PD compared with siblings of controls (RR, 7.9; 95% CI, 2.5-25.5; p = 0.0005), whereas parents of early-onset PD probands were not at significantly increased risk compared with parents of controls (RR, 1.7; 95% CI, 0.9-3.3; p = 0.2). In late-onset families, both siblings (RR, 3.6; 95% CI, 1.3-10.3; p = 0.02) and parents (RR, 2.5; 95% CI, 1.4-4.6; p = 0.003) were at increased risk compared with control relatives. This pattern is consistent with an autosomal recessive contribution to the inheritance of early but not late-onset PD. Genetic factors are important in both early- and late-onset PD, but specific genes and mode of inheritance may differ between the two groups.
遗传因素在早发型与晚发型帕金森病（PD）中的作用存在争议。我们评估了221名发病年龄在50岁及以下的PD先证者以及266名发病年龄大于50岁的PD先证者的一级亲属相较于409名对照先证者的一级亲属患PD风险增加的程度。早发型PD先证者的一级亲属（风险比[RR]，2.9；95%置信区间[CI]，1.6 - 5.0；p = 0.0002）和晚发型PD先证者的一级亲属（RR，2.7；95% CI，1.6 - 4.4；p = 0.0002）与对照先证者的一级亲属相比，患PD的风险相似。然而，早发型PD先证者的兄弟姐妹相较于对照先证者的兄弟姐妹患PD的风险显著增加（RR，7.9；95% CI，2.5 - 25.5；p = 0.0005），而早发型PD先证者的父母相较于对照先证者的父母患PD的风险未显著增加（RR，1.7；95% CI，0.9 - 3.3；p = 0.2）。在晚发型家族中，兄弟姐妹（RR，3.6；95% CI，1.3 - 10.3；p = 0.02）和父母（RR，2.5；95% CI，1.4 - 4.6；p = 0.003）相较于对照亲属患PD的风险均增加。这种模式与常染色体隐性遗传对早发型而非晚发型PD的遗传作用一致。遗传因素在早发型和晚发型PD中均很重要，但两组的特定基因和遗传模式可能有所不同。
