کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4180830 1276621 2006 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Haplotype Analysis Reveals Tryptophan Hydroxylase (TPH) 1 Gene Variants Associated with Major Depression
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی روانپزشکی بیولوژیکی
پیش نمایش صفحه اول مقاله
Haplotype Analysis Reveals Tryptophan Hydroxylase (TPH) 1 Gene Variants Associated with Major Depression
چکیده انگلیسی

BackgroundTryptophan hydroxylase (TPH) is the rate-limiting enzyme in the biosynthesis of serotonin (5-HT) and might be related to the pathogenesis of major depression (MD). Two isoforms are known, TPH-1 and TPH-2. Tryptophan hydroxylase-1 association with MD is still debated.MethodsA 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.ResultsSix 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 < 10−5). A “sliding window” analysis attributed the strongest disease association to a haplotype configuration localized between introns 7 and 8 (p < 10−5).ConclusionsHaplotype analysis indicates that TPH-1 associates with MD. The most common TPH-1 variants appear to carry no risk, while some of the less frequent variants might contribute to genetic predisposition to MD.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biological Psychiatry - Volume 59, Issue 4, 15 February 2006, Pages 295–300
نویسندگان
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