Haplotype analysis reveals tryptophan hydroxylase (TPH) 1 gene variants associated with major depression
Haplotype analysis reveals tryptophan hydroxylase (TPH) 1 gene variants associated with major depression
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DOI：
10.1016/j.biopsych.2005.07.034
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发表时间：
2006-02-15
影响因子：
10.6
通讯作者：
Leopardi, R
中科院分区：
文献类型：
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作者：
Gizatullin, R;Zaboli, G;Leopardi, R
背景：色氨酸羟化酶(TPH)是5-羟色胺(5-HT)生物合成的限速酶，可能与抑郁症的发病机制有关。已知有两种异构体。TPH-1和TPH-2。色氨酸羟基酶-1与MD的相关性仍存在争议。方法：采用单核苷酸多态(SNP)筛选策略，确定TPH-1单倍型跨越29kb基因长度的23kb(Kb)。对228例MD患者和253例健康对照进行了基因分型。结果：在MD患者和对照组中均发现6个SNPs处于连锁不平衡状态，提示为单倍型区块结构。单标记关联分析显示，只有一个SNP与MD显著相关。有几种单倍型与MD相关。当所有6个座位的单倍型被分成两组时，高于或低于5%的阈值。低于5%的复合单倍型组与疾病相关(31.6%比18.0%，P
Background: Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in the biosynthesis of serotonin (5-HT) and might be related to the pathogenesis of major depression (AID). Two isoforms are known. TPH-1 and TPH-2. Tryptophan hydroxylase-1 association with MD is still debated.Methods: A single nucleotide polymorphism (SNP) screening strategy was used to define TPH-1 haplotypes spanning over 23 kilobase (kb) of the 29 kb gene length. Genotyping was performed in 228 MD patients and 253 healthy control subjects.Results: Six SNPs were found at linkage disequilibrium in both patients and control subjects, suggesting a haplotype block structure. Single marker association analyses showed only one SNP significantly associated with MD. Several haplotypes were associated with MD. When all six locus haplotypes were divided into two groups, above or below a 5% threshold. the compound haplotype group below a 5% frequency resulted as associated with the disease (31.6% vs. 18.0% in control subjects, p