人类酪氨酸激酶B神经营养因子受体基因内的核苷酸序列变异：与反社会型酒精依赖的关联
Nucleotide sequence variation within the human tyrosine kinase B neurotrophin receptor gene: association with antisocial alcohol dependence.
作者信息
Xu K, Anderson T R, Neyer K M, Lamparella N, Jenkins G, Zhou Z, Yuan Q, Virkkunen M, Lipsky R H
机构信息
Sections on Molecular Genetics and Human Genetics, Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA.
出版信息
Pharmacogenomics J. 2007 Dec;7(6):368-79. doi: 10.1038/sj.tpj.6500430. Epub 2007 Jan 2.
Abstract
To identify sequence variants in genes that may have roles in neuronal responses to alcohol, we resequenced the 5' region of tyrosine kinase B neurotrophin receptor gene (NTRK2) and determined linkage disequilibrium (LD) values, haplotype structure, and performed association analyses using 43 single nucleotide polymorphisms (SNPs) covering the entire NTRK2 region in a Finnish Caucasian sample of 229 alcohol-dependent subjects with antisocial personality disorder (ASPD) and 287 healthy controls. Individually, three SNPs were associated with alcohol dependence and alcohol abuse (AD) (P-value from 0.0019 to 0.0059, significance level was set at P<or=0.01 corrected for multiple testing), whereas a common 18 locus haplotype within the largest LD block of NTRK2, a 119-kb region containing the 5' flanking region and exons 1-15, was marginally overrepresented in control subjects compared to AD individuals (global P=0.057). Taken together, these results support a role for the NTRK2 gene in addiction in a Caucasian population with AD and a subtype of ASPD.
摘要
为了鉴定可能在神经元对酒精反应中起作用的基因中的序列变异，我们对酪氨酸激酶B神经营养因子受体基因（NTRK2）的5'区域进行了重测序，确定了连锁不平衡（LD）值、单倍型结构，并使用覆盖整个NTRK2区域的43个单核苷酸多态性（SNP），在229名患有反社会人格障碍（ASPD）的酒精依赖受试者和287名健康对照组成的芬兰白种人样本中进行了关联分析。单独来看，有三个SNP与酒精依赖和酒精滥用（AD）相关（P值从0.0019到0.0059，多重检验校正后的显著性水平设定为P≤0.01），而在NTRK2最大LD块内一个常见的18位点单倍型，即一个包含5'侧翼区域和外显子1 - 15的119 kb区域，与AD个体相比，在对照受试者中略有过度代表（全局P = 0.057）。综上所述，这些结果支持NTRK2基因在患有AD和ASPD亚型白种人群体的成瘾过程中发挥作用。
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