No association between common variations in the neuronal nicotinic acetylcholine receptor alpha2 subunit gene (CHRNA2) and bipolar I disorder.
No association between common variations in the neuronal nicotinic acetylcholine receptor alpha2 subunit gene (CHRNA2) and bipolar I disorder.
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神经元烟碱乙酰胆碱受体 α2 亚基基因 (CHRNA2) 的常见变异与 I 型双相情感障碍之间没有关联。
DOI：
10.1016/j.psychres.2005.04.004
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发表时间：
2005
影响因子：
11.3
通讯作者：
Berrettini,WadeH
中科院分区：
文献类型：
--
作者：
Lohoff,FalkW;Ferraro,ThomasN;McNabb,Leilah;Schwebel,Candice;Dahl,JohnP;Doyle,GlennA;Buono,RussellJ;Berrettini,WadeH
神经元烟碱乙酰胆碱受体α 2亚基基因（CHRNA 2）定位于染色体8 p21 -22上的双极易感基因座。考虑到神经元烟碱乙酰胆碱受体的生物学作用和精神疾病中尼古丁依赖的实质性共病，CHRNA 2基因是双相情感障碍（BPD）的合理候选基因。我们在一项病例对照关联研究中检验了CHRNA 2基因变异赋予双相I型情感障碍易感性的假设。从345名无关的双相I型患者和273名对照样本中获得了CHRNA 2基因的一种氨基酸取代多态性（Ala 125 Thr）和五种非编码变异的基因型。采用卡方列联分析比较各组间基因型和等位基因频率。计算标记之间的连锁不平衡（LD），并比较各组之间的估计单倍型频率。我们观察到双相情感障碍患者和对照组之间所有六种变异的基因型和等位基因频率没有统计学显著差异，但我们确实证明了整个基因的强LD。单倍型分析表明，没有等位基因的组合与疾病有关。我们的研究结果表明，CHRNA 2基因的常见变异不太可能使该样本对BPD易感。需要进一步的研究来阐明染色体8 p21 -22上的BPD易感位点。
The neuronal nicotinic acetylcholine receptor alpha2 subunit gene (CHRNA2) maps to the bipolar susceptibility locus on chromosome 8p21–22. Given the biological role of the neuronal nicotinic acetylcholine receptors and the substantial comorbidity of nicotine dependence in psychiatric disorders, the CHRNA2 gene is a plausible candidate gene for bipolar disorder (BPD). We tested the hypothesis that variations in the CHRNA2 gene confer susceptibility to bipolar I disorder in a case-control association study. Genotypes of one amino acid substitution polymorphism (Ala125Thr) and five non-coding variations across the CHRNA2 gene were obtained from 345 unrelated bipolar I patients and 273 control samples. Genotypes and allele frequencies were compared between groups using chi-square contingency analysis. Linkage disequilibrium (LD) between markers was calculated, and estimated haplotype frequencies were compared between groups. We observed no statitistically significant difference in genotype and allele frequencies for all six variations between bipolar patients and controls, but we did demonstrate strong LD throughout the gene. Haplotype analysis showed that no combinations of alleles were associated with illness. Our results suggest that common variations in the CHRNA2 gene are unlikely to confer susceptibility to BPD in this sample. Further studies are required to elucidate the susceptibility locus for BPD on chromosome 8p21–22.