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J Cell Mol Med. 2018 Mar;22(3):1778-1791. doi: 10.1111/jcmm.13459. Epub 2018 Jan 5.

Association between single nucleotide polymorphisms of TPH1 and TPH2 genes, and depressive disorders.

Author information

1
Laboratory of Medical Genetics, Department of Molecular Genetics, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland.
2
Department of Medical Biochemistry, Medical University of Lodz, Lodz, Poland.
3
Department of General Biochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland.
4
Department of Adult Psychiatry, Medical University of Lodz, Lodz, Poland.

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Abstract

Tryptophan catabolites pathway disorders are observed in patients with depression. Moreover, single nucleotide polymorphisms of tryptophan hydroxylase genes may modulate the risk of depression occurrence. The objective of our study was to confirm the association between the presence of polymorphic variants of TPH1 and TPH2 genes, and the development of depressive disorders. Six polymorphisms were selected: c.804-7C>A (rs10488682), c.-1668T>A (rs623580), c.803+221C>A (rs1800532), c.-173A>T (rs1799913)-TPH1, c.-1449C>A (rs7963803), and c.-844G>T (rs4570625)-TPH2. A total of 510 DNA samples (230 controls and 280 patients) were genotyped using TaqMan probes. Among the studied polymoorphisms, the G/G genotype and G allele of c.804-7C>A-TPH1, the T/T homozygote of c.803+221C>A-TPH1, the A/A genotype and A allele of c.1668T>A-TPH1, the G/G homozygote and G allele of c.-844G>T-TPH2, and the C/A heterozygote and A allele of c.-1449C>A-TPH2 were associated with the occurrence of depression. However, the T/T homozygote of c.-1668T>A-TPH1, the G/T heterozygote and T allele of c.-844G>T-TPH2, and the C/C homozygote and C allele of c.-1449C>A-TPH2 decreased the risk of development of depressive disorders. Each of the studied polymorphisms modulated the risk of depression for selected genotypes and alleles. These results support the hypothesis regarding the involvement of the pathway in the pathogenesis of depression.

KEYWORDS:

depression; single nucleotide polymorphism; tryptophan catabolites pathways; tryptophan hydroxylase

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