Alzheimer's disease in Finnish twins
Alzheimer's disease in Finnish twins
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DOI：
10.1016/s0140-6736(96)91272-6
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发表时间：
1996-03-02
期刊：
影响因子：
168.9
通讯作者：
Sourander, L
中科院分区：
文献类型：
--
作者：
Raiha, I;Kaprio, J;Sourander, L
背景 阿尔茨海默病 (AD) 的遗传学尚不清楚。尽管大多数病例是散发性的，但一半散发性 AD 患者有阳性家族史。遗传传播的方式和环境因素的作用尚不清楚。本研究的目的是探讨双胞胎队列中遗传因素对 AD 发病机制的影响。 方法 芬兰双胞胎队列由 1958 年之前出生的所有芬兰同性双胞胎组成，其中双胞胎均于 1975 年存活。双胞胎总数为 13 888 对，其中 4 307 对是同卵双胞胎 (MZ)，9 581 对是双卵双胞胎 (DZ)。这些数据与 1972 年至 1991 年间的医院出院登记册相关联，以识别患有痴呆症或相关疾病的双胞胎作为出院诊断。登记处的链接总共产生了 285 个双胞胎个体。对这对双胞胎及其双胞胎的医疗记录进行了审查，以确认痴呆症（AD、血管性痴呆、混合性痴呆和其他痴呆）并对其进行分类。对 AD 的发病率、一致性和发病年龄进行了检查。结果：同卵双胞胎中 AD 的发病率显着高于异卵双胞胎，调整后的同卵双胞胎/异卵双胞胎发病率为 1.8（95% 置信区间为 1.2 至 2.7）。相比之下，MZ 和 DZ 个体之间血管性或混合性痴呆的发生率没有差异（血管性痴呆的 MZ/DZ 比率为 0.6 [0.3 至 1.2]），混合性痴呆为 1.0 [0.5 至 2.1]。 AD 的成对一致性在 MZ 对中为 18.6%，在 DZ 对中为 4.7%，相应的先证一致性率为 31.3% 和 9.3%。血管性痴呆的配对一致性在 MZ 配对中为 18.2%，在 DZ 配对中为 6.7%，相应的先证率分别为 30.8% 和 12.5%。两对一致的 MZ 个体中 AD 的发病年龄相同，相差高达 15 岁。解释 MZ 个体中 AD 的发病率高于 DZ 个体，这可能为 AD 的病因学提供了线索。 MZ 对的较高一致性证实了主要遗传成分的贡献，同时表明需要识别环境触发因素。
Background The genetics of Alzheimer's disease (AD) are obscure. Although most cases are sporadic half the patients with sporadic AD have a positive family history. The mode of genetic transmission and the role of environmental factors are unknown. The purpose of this study was to examine the contribution of genetic factors to the pathogenesis of AD in a twin cohort.Methods The Finnish Twin Cohort consists of all Finnish same-sexed twin pairs born before 1958 with both co-twins alive in 1975. The total number of twin pairs is 13 888, of whom 4307 are monozygotic (MZ) and 9581 are dizygotic (DZ). These data were linked with the Hospital Discharge Register from 1972 to 1991 to identify twins who had dementia or related disease as a discharge diagnosis. The linkage of the registries yielded a total of 285 twin individuals. The medical records of these twins and their co-twins were reviewed to confirm and classify dementia (AD, vascular dementia, mixed dementia, and other dementia). The incidence, concordance, and age at onset of AD were examined.Findings The incidence of AD was significantly higher in MZ than in DZ twin individuals, with an adjusted MZ/DZ incidence ratio of 1.8 (95% confidence intervals 1.2 to 2.7). In contrast, the incidence of vascular or mixed dementia did not differ between MZ and DZ individuals (MZ/DZ ratio 0.6 [0.3 to 1.2]) for vascular and 1.0 [0.5 to 2.1] for mixed dementia). The pairwise concordance for AD was 18.6% in MZ pairs and 4.7% in DZ pairs and the corresponding probandwise concordance rates were 31.3% and 9.3%. The pairwise concordance for vascular dementia was 18.2% in MZ pairs and 6.7% in DZ pairs with corresponding probandwise rates of 30.8% and 12.5%. The onset age of AD in concordant MZ pairs was identical in two pairs and diverged by up to 15 years.Interpretation The higher incidence of AD in MZ individuals than in DZ individuals may provide a clue to the aetiology of AD. The higher concordance rate of MZ pairs confirms the contribution of the major genetic component while indicating the need to identify environmental triggers.