Percy Maire E, Potyomkina Zoya, Dalton Arthur J, Fedor Bettye, Mehta Pankaj, Andrews David F, Mazzulli Tony, Murk Lillian, Warren Andrew C, Wallace Robyn A, Chau Hien, Jeng Winnie, Moalem Sharon, O'Brien Lisa, Schellenberger Sonia, Tran Helen, Wu Linda
Department of Physiology, University of Toronto, Toronto, Ontario, Canada.
Am J Med Genet A. 2003 Jul 15;120A(2):191-8. doi: 10.1002/ajmg.a.20099.
Dementia of the Alzheimer type (DAT) is common in older persons with Down syndrome (DS). There are three common alleles of the apolipoprotein E (ApoE) gene (Sigma 2, Sigma 3, and Sigma 4) resulting in three different isoforms (E2, E3, and E4) and six different genotypes (2,2; 2,3; 2,4; 3,3; 3,4; and 4,4). Sigma 4 is a risk factor for DAT whereas Sigma 2 appears prophylactic. As hepatitis B virus (HBV) infection and hypothyroidism also are common in DS, we evaluated associations between ApoE type, HBV status, and thyroid status in a sample of older persons with DS (n = 55; mean age, 44.3 +/- 10.8 years) using chi-squared analysis. Participants were classified as E2 (2,2 or 2,3), E3 (3,3), or E4 (3,4 or 4,4); positive for markers of HBV infection in the present or past (i.e., total HBcAb+ and/or HBsAg+ with or without infectivity, defined as HBV+) or negative for markers of HBV infection (defined as HBV-) and, currently receiving thyroid hormone supplement (defined as "hypothyroidism") or having normal thyroid function. The majority of the HBV+ were currently HBcAb+ and HBsAb+, but not HBsAg+. In females, there was an ApoE allele effect on thyroid status (P < or = 0.01), E2 being negatively (P < or = 0.01) and E4 being positively (P < or = 0.05) associated with "hypothyroidism". There was no evidence for an ApoE allele effect on thyroid status in males. There was no evidence for an ApoE allele effect on HBV status, or for an HBV status effect on thyroid status. As thyroid status can affect cognitive function, ApoE allele effects in DAT may, in part, be thyroid effects.
阿尔茨海默型痴呆（DAT）在老年唐氏综合征（DS）患者中很常见。载脂蛋白E（ApoE）基因有三种常见等位基因（ε2、ε3和ε4），产生三种不同的异构体（E2、E3和E4）以及六种不同的基因型（2,2；2,3；2,4；3,3；3,4；和4,4）。ε4是DAT的一个风险因素，而ε2似乎具有预防作用。由于乙型肝炎病毒（HBV）感染和甲状腺功能减退在DS患者中也很常见，我们使用卡方分析评估了一组老年DS患者（n = 55；平均年龄，44.3 +/- 10.8岁）中ApoE类型、HBV状态和甲状腺状态之间的关联。参与者被分为E2（2,2或2,3）、E3（3,3）或E4（3,4或4,4）；目前或过去HBV感染标志物呈阳性（即总HBcAb +和/或HBsAg +，无论有无传染性，定义为HBV +）或HBV感染标志物呈阴性（定义为HBV -），以及目前正在接受甲状腺激素补充治疗（定义为“甲状腺功能减退”）或甲状腺功能正常。大多数HBV +患者目前HBcAb +和HBsAb +，但HBsAg -。在女性中，ApoE等位基因对甲状腺状态有影响（P≤0.01），E2与“甲状腺功能减退”呈负相关（P≤0.01），E4与“甲状腺功能减退”呈正相关（P≤0.05）。在男性中没有证据表明ApoE等位基因对甲状腺状态有影响。没有证据表明ApoE等位基因对HBV状态有影响，也没有证据表明HBV状态对甲状腺状态有影响。由于甲状腺状态会影响认知功能，DAT中ApoE等位基因的影响可能部分是甲状腺的影响。
