Advances in Clinical and Experimental Medicine
2017, vol. 26, nr 8, November, p. 1269–1273
Publication type: original article
Investigation of DNA repair genes in patients with obsessive-compulsive disorder
1 Department of Molecular Medicine, Institute of Experimental Medicine, Istanbul University, Turkey
2 Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Istanbul Yeni Yuzyil University, Turkey
3 Department of Neuroscience, Institute of Experimental Medicine, Istanbul University, Turkey
4 Institute for Experimental Medicine Research, Istanbul University, Turkey
Background. Obsessive-compulsive disorder (OCD) is a major psychiatric disorder identified mostly by obsessions and compulsions. Molecular genetic and gene-expression studies focused on familial and twin cases have shown a wide variety of variant genes related to OCD.
Objectives. The aim of the study was to investigate DNA repair genes as potential molecular markers in OCD by evaluating the distribution of polymorphisms of DNA repair genes in OCD patients.
Material and Methods. The study included 100 case subjects with OCD and 122 unrelated healthy controls. Genotyping of XRCC1, XRCC3, XPD, XPG, APE1 and HOGG1 was performed by polymerase chain reactionrestriction fragment length polymorphism.
Results. Significant differences were found for XPD and genotype frequencies. Likewise, the frequency of the XPD Lys+ genotype was significantly increased in the patients as compared to the controls, and carriers of the Lys+ genotype had an increased risk for OCD (p = 0.027). The XPD Lys/Lys genotype frequency was also increased in the patients in comparison to the controls (p < 0.001). XPD Gln+ frequencies were higher in the controls than in the patients, and carriers of the Gln+ genotype showed decreased levels of OCD risk (p < 0.001). XPD Lys/Lys genotype frequency and XPD Gln+ frequency are also significantly associated even after Bonferroni correction (p < 0.008).
Conclusion. The findings suggest that XPD Lys/Lys might play a facilitating role in the development of OCD.
polymorphism, obsessive-compulsive disorder, DNA repair, XPD
- Nestadt G, Grados M, Samuels JF. Genetics of OCD. Psychiatr Clin North Am. 2010;33:141–158.
- Nestadt G, Samuels JF, Romanoski AJ, et al. Obsessions and compulsions in the community. Acta Psychiatr Scand. 1994;89:219–224.
- Nestadt G, Bienvenu OJ, Cai G, et al. Incidence of obsessive-compulsive disorder in adults. J Nerv Ment Dis. 1998;186:401–406.
- Steketee G. Disability and family burden in obsessive-compulsive disorder. Can J Psychiatry. 1997;142:919–928.
- Pauls DL. The genetics of obsessive compulsive disorder: A review of the evidence. Am J Med Genet Part C Semin Med Genet. 2008;148:133–139.
- Pauls DL. The genetics of obsessive-compulsive disorder: A review. Dialogues Clin Neurosci. 2010;12:149–163.
- Stein DJ. Advances in the neurobiology of obsessive-compulsive disorder: Implications for conceptualizing putative obsessive-compulsive and spectrum disorders. Psychiatr Clin North Am. 2000;23:545–562.
- Black DW, Noyes R Jr. Goldstein RB, et al. A family study of obsessive-compulsive disorder. Arch Gen Psychiatry. 1992;49:362–368.
- Pauls DL. The genetics of obsessive compulsive disorder: A review of the evidence. Dialogues Clin Neurosci. 2010;12(2):149–163.
- Fyer AJ, Lipsitz JD, Mannuzza S, Aronowitz B, Chapman TF. A direct interview family study of obsessive-compulsive disorder I. Psychol Med. 2005;35:1611–1621.
- Wendland JR, Moya PR, Kruse MR, et al. A novel, putative gain of function haplotype at SLC6A4 associates with obsessive-compulsive disorder. Hum Mol Genet. 2008;17:717–723.
- Krupa R, Sobczuk A, Popławski T, Wozniak K, Blasiak J. DNA damage and repair in endometrial cancer in correlation with the HOGG1 and RAD51 genes polymorphism. Mol Biol Rep. 2011;38(2):1163–1170.
- Ashton KA, Proietto A, Otton G, et al. Estrogen receptor polymorphisms and the risk of endometrial cancer. BJOG. 2009;116(8):1053–1061.
- Attar R, Cacina C, Sozen S, Attar E, Agachan B. DNA repair genes in endometriosis. Genet Mol Res. 2010;9(2):629–636.
- Wood RD, Mitchell M, Sgouros J, Lindahl T. Human DNA repair genes. Science. 2001;291(5507):128–129.
- Wang M, Qin C, Zhu J, et al. Genetic variants of XRCC1, APE1, and ADPRT genes and risk of bladder cancer. DNA Cell Biol. 2010;29(6):303–314.
- Robertson AB, Klungland A, Rognes T, Leiros I. DNA repair in mammalian cells. Base excision repair: The long and short of it. Cell Mol Life Sci. 2009;66(6):981–993.
- Li Z, Guan W, Li MX, et al. Genetic polymorphism of DNA base-excision repair genes (APE1, OGG1 and XRCC1) and their correlation with risk of lung cancer in a Chinese population. Arch Med Res. 2011;42(3):226–234.
- Canbay E, Cakmakoglu B, Zeybek U, et al. Association of APE1 and HOGG1 polymorphisms with colorectal cancer risk in a Turkish population. Curr Med Res Opin. 2011;7(7):1295–1302.
- Chang-Claude J, Popanda O, Tan XL, et al. Association between polymorphisms in the DNA repair genes, XRCC1, APE1, and XPD and acute side effects of radiotherapy in breast cancer patients. Clin Cancer Res. 2005;11(13):4802–4809.
- Blasiak J, Synowiec E, Salminen A, Kaarniranta K. Genetic variability in DNA repair proteins in age-related macular degeneration. Int J Mol Sci. 2012;13:13378–13397.
- Szumilas M. Explaining odds ratios. J Can Acad Child Adolesc Psychiatry. 2010;19:3.
- Salah GB, Fendri-Kriaa N, Kamoun H, Kallabi F, Mkaouar-Rebai E, Fourati A. An interethnic variability and a functional prediction of DNA repair gene polymorphisms: The example of XRCC3 (p.Thr241>Met) and XPD (p.Lys751>Gln) in a healthy Tunisian population. Mol Biol Rep. 2012;39:9639–9647.
- Calvocoressi L, Libman D, Vegso SJ, McDougle CJ, Price LH. Global functioning of inpatients with obsessive-compulsive disorder, schizophrenia, and major depression. Psychiatric Services. 1998;49:379–381.
- Karno M, Golding JM, Sorenson SB, Burnam MA. The epidemiology of obsessive-compulsive disorder in five U.S. communities. Arch Gen Psychiatry. 1988;45:1084–1099.
- Weissman MM, Bland RC, Canino GJ, et al. The cross national epidemiology of obsessive compulsive disorder. J Clin Psychiatry. 1994;55:5–10.
- Eaton WW, Martins SS, Nestadt GO, Bienvenu OJ, Clarke D, Alexandre P. The burden of mental disorders. Epidemiol Rev. 2008;30:1–14.
- Shugart YY, Samuels J, Willour VL, et al. Genomewide linkage scan for obsessive-compulsive disorder: Evidence for susceptibility loci on chromosomes 3q, 7p, 1q, 15q, and 6q. Molecular Psychiatry. 2006;11:763–770.
- Benhamou S, Sarasin A. ERCC2/XPD gene polymorphisms and lung cancer: A HuGE review. Am J Epidemiol. 2005;161:1–14.
- Friedberg EC. DNA damage and repair. Nature. 2003;421:436–440.
- Wood RD, Mitchell M, Sgouros J, Lindahl T. Human DNA repair genes. Science. 2001;291:1284–1289.
- Olver JS, O’Keefe G, Jones GR, et al. Dopamine D(1) receptor binding in the anterior cingulate cortex of patients with obsessive-compulsive disorder. Psychiatry Res. 2010;83:85–88.
- Gencer M, Dasdemir S, Cakmakoglu B, et al. DNA repair genes in Parkinson’s disease. Genet Test Mol Biomarkers. 2012;16:504–507.
- Dobbin MM, Madabhushi R, Pan L, et al. SIRT1 collaborates with ATM and HDAC1 to maintain genomic stability in neurons. Nat Neurosci. 2013;16(8):1008–1015.
- Wang WY, Pan L, Su SC, et al. Interaction of FUS and HDAC1 regulates DNA damage response and repair in neurons. Nat Neurosci. 2013;16(10):1383–1391.
- Weissman L, Jo DG, Sorensen MM, et al. Defective DNA base excision repair in brain from individuals with Alzheimer’s disease and amnestic mild cognitive impairment. Nucleic Acids Res. 2007;35(16):5545–5555.
- Fishel ML, Vasko MR, Kelley MR. DNA repair in neurons: So if they don’t divide, what’s to repair? Mutat Res. 2007;614(1–2):24–36.
- Coppede F, Migliore L. DNA damage and repair in Alzheimer’s disease. Curr Alzheimer Res. 2009;6(1):36–47.