Piotr Czarny1, Dominik Kwiatkowski1, Piotr Galecki2, Monika Talarowska2, Agata Orzechowska2, Kinga Bobinska2, Anna Bielecka-Kowalska3, Janusz Szemraj4, Michael Maes5, Kuan-Pin Su6, Tomasz Sliwinski7. 1. University of Lodz, Department of Molecular Genetics, Poland. 2. Medical University of Lodz, Department of Adult Psychiatry, Poland. 3. Non-public Medical Center "Akoria", Poland. 4. Medical University of Lodz, Department of Medical Biochemistry, Poland. 5. IMPACT Strategic Research Centre, Deakin University, School of Medicine, Barwon Health, Geelong, Australia; Department of Psychiatry, Chulalongkorn University, Bangkok, Thailand; Health Sciences Graduate Program, Health Sciences Center, State University of Londrina, Brazil. 6. Department of Psychiatry and Mind-Body Interface Laboratory (MBI-Lab), China Medical University Hospital, Taichung, Taiwan. 7. University of Lodz, Department of Molecular Genetics, Poland. Electronic address: tomsliw@biol.uni.lodz.pl.
Abstract
BACKGROUND: An elevated levels oxidative modified DNA bases and a decreased efficiency of oxidative DNA damage repair were found in patients with depression disorders, including recurrent type (rDD). The glycosylases are involved in base excision repair (BER), which eliminates oxidative DNA damage. Therefore, we genotyped the single nucleotide polymorphisms (SNPs) of genes encoding three glycosylases: hOGG1, MUTYH and NEIL1. METHODS: We selected three polymorphisms: c.977C > G - hOGG1 (rs1052133), c.972G > C - MUTYH (rs3219489) and c.*589G > C - NEIL1 (rs4462560). A total of 555 DNA samples (257 cases and 298 controls) were genotyped using TaqMan probes. RESULTS: The C/C genotype and allele C of the c.*589G > C decreased the risk of rDD occurrence, while the G/G genotype and allele G of the same SNP increased the risk. This polymorphism had a stronger association with early-onset depression (patients with first episode <35 years of age) than with late-onset depression (first episode ≥ 35 years of age). We did not find any significant differences in distribution of alleles and genotypes of other SNPs; however, the G/G genotype of the c.972G > C increased the risk of late-onset rDD. We also found that combined genotype C/C-C/C of c.977C > G and c.*589G > C significantly reduced the risk of rDD. LIMITATIONS: Limited sample size and ethnic homogeneity of the studied population. CONCLUSION: This is the first study to show that SNPs of genes involved in DNA repair, particularly in BER pathway, may modulate the risk of rDD. These results further support the hypothesis on the involvement of DNA repair mechanisms in pathogenesis of depression.
BACKGROUND: An elevated levels oxidative modified DNA bases and a decreased efficiency of oxidative DNA damage repair were found in patients with depression disorders, including recurrent type (rDD). The glycosylases are involved in base excision repair (BER), which eliminates oxidative DNA damage. Therefore, we genotyped the single nucleotide polymorphisms (SNPs) of genes encoding three glycosylases: hOGG1, MUTYH and NEIL1. METHODS: We selected three polymorphisms: c.977C > G - hOGG1 (rs1052133), c.972G > C - MUTYH (rs3219489) and c.*589G > C - NEIL1 (rs4462560). A total of 555 DNA samples (257 cases and 298 controls) were genotyped using TaqMan probes. RESULTS: The C/C genotype and allele C of the c.*589G > C decreased the risk of rDD occurrence, while the G/G genotype and allele G of the same SNP increased the risk. This polymorphism had a stronger association with early-onset depression (patients with first episode <35 years of age) than with late-onset depression (first episode ≥ 35 years of age). We did not find any significant differences in distribution of alleles and genotypes of other SNPs; however, the G/G genotype of the c.972G > C increased the risk of late-onset rDD. We also found that combined genotype C/C-C/C of c.977C > G and c.*589G > C significantly reduced the risk of rDD. LIMITATIONS: Limited sample size and ethnic homogeneity of the studied population. CONCLUSION: This is the first study to show that SNPs of genes involved in DNA repair, particularly in BER pathway, may modulate the risk of rDD. These results further support the hypothesis on the involvement of DNA repair mechanisms in pathogenesis of depression.
Authors: Piotr Czarny; Dominik Kwiatkowski; Monika Toma; Piotr Gałecki; Agata Orzechowska; Kinga Bobińska; Anna Bielecka-Kowalska; Janusz Szemraj; Michael Berk; George Anderson; Tomasz Śliwiński Journal: Med Sci Monit Date: 2016-11-20