Philibert R A, Cheung D, Welsh N, Damschroder-Williams P, Thiel B, Ginns E I, Gershenfeld H K
Department of Psychiatry, University of College of Medicine, Iowa City, Iowa, USA.
Am J Med Genet. 2001 Apr 8;105(3):291-4. doi: 10.1002/ajmg.1322.
Previous studies provide evidence for a genetic component for susceptibility to bipolar affective disorder (BPAD) in the old-order Amish population. El-Mallakh and Wyatt [1995: Biol Psychiatry 37:235-244] have suggested that the Na(+),K(+)-ATPase may be a candidate gene for BPAD. This study examines the relationship between BPAD in the old-order Amish cohort and the Na(+),K(+)-ATPase alpha1 and beta3 subunit genes (ATP1A3, ATP1B3). A total of 166 sibling pairs were analyzed for linkage via nonparametric methods. Suggestive levels of statistical significance were not reached in any stratification model for affective illness. Overall, the results do not support linkage of bipolar disorder to the Na(+),K(+)-ATPase alpha subunit gene (ATP1A3) and beta subunit gene (ATP1B3) in these old-order Amish families and they show that these Na(+),K(+)-ATPase subunit genes are not major effect genes (>or=fourfold increased genetic risk of disease) for BPAD in the old-order Amish pedigrees. We cannot exclude other genetic variants of the Na(+),K(+)-ATPase hypothesis for BPAD, whereby other loci may modifying Na(+),K(+)-ATPase activity.
先前的研究为老派阿米什人群中双相情感障碍（BPAD）易感性的遗传成分提供了证据。El-Mallakh和Wyatt[1995年：《生物精神病学》37卷：235 - 244页]提出，钠钾ATP酶可能是BPAD的候选基因。本研究考察了老派阿米什队列中的BPAD与钠钾ATP酶α1和β3亚基基因（ATP1A3、ATP1B3）之间的关系。通过非参数方法对总共166对同胞进行了连锁分析。在任何情感障碍分层模型中均未达到统计学意义的提示水平。总体而言，结果不支持双相情感障碍与这些老派阿米什家族中的钠钾ATP酶α亚基基因（ATP1A3）和β亚基基因（ATP1B3）存在连锁关系，并且表明这些钠钾ATP酶亚基基因不是老派阿米什家系中BPAD的主要效应基因（疾病遗传风险增加四倍或以上）。我们不能排除钠钾ATP酶假说中BPAD的其他遗传变异，即其他基因座可能调节钠钾ATP酶的活性。
