Zubenko G S, Stiffler J S, Hughes H B, Hurtt M R, Kaplan B B
Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh, Pennsylvania 15213, USA.
Am J Med Genet. 1998 Mar 28;81(2):196-205.
As the initial step in a systematic genome survey, 16 simple sequence tandem repeat polymorphisms that span the X chromosome at an average spacing of 10 cM were examined for allelic associations with typical-onset Alzheimer's disease (AD). The efficiency of this survey was substantially enhanced by genotyping pools of genomic DNA from 50 autopsy-confirmed AD cases and 50 autopsied controls who were similar in sex ratio, race, and age at death. The frequency of the DXS1047 202-bp allele was twice as common among AD cases (0.45 +/- S.E. 0.06) than controls (0.22 +/- S.E. 0.05), a finding that was reproduced in an independent and geographically disparate sample. Consistent with Hardy-Weinberg equilibrium, the proportion of women with AD who carried the 202-bp allele, 73% was nearly double that observed for men with AD, 38%. However, the frequency of the 202-bp allele was similar for men and women and the presence of this allele did not affect the age at onset of dementia in either sex. Furthermore, the frequency of the DXS1047 202-bp allele in AD cases and controls was unaffected by the APOE genotype, indicating that these two loci modulate AD risk independently. Finally, the frequency of the 202-bp allele among 50 autopsy-confirmed cases of Parkinson's disease (0.29 +/- S.E. 0.06) was indistinguishable from the control value, reflecting relative specificity for this allelic association with AD.
作为系统基因组调查的第一步，我们检测了16个平均间距为10厘摩跨越X染色体的简单序列串联重复多态性，以研究其与典型发病的阿尔茨海默病（AD）的等位基因关联。通过对50例经尸检确诊的AD病例和50例经尸检的对照者的基因组DNA池进行基因分型，大大提高了这项调查的效率，这些对照者在性别比例、种族和死亡年龄方面相似。DXS1047 202碱基对等位基因在AD病例中的频率（0.45±标准误0.06）是对照组（0.22±标准误0.05）的两倍，这一发现已在一个独立的、地理位置不同的样本中得到重现。与哈迪-温伯格平衡一致，携带202碱基对等位基因的AD女性比例为73%，几乎是AD男性（38%）的两倍。然而，202碱基对等位基因在男性和女性中的频率相似，并且该等位基因的存在对两性痴呆发病年龄均无影响。此外，AD病例和对照者中DXS1047 202碱基对等位基因的频率不受APOE基因型的影响，表明这两个位点独立调节AD风险。最后，50例经尸检确诊的帕金森病病例中202碱基对等位基因的频率（0.29±标准误0.06）与对照值无差异，反映了该等位基因与AD关联的相对特异性。
