The effect of glial derived neurotrophic factor SNPs on the development of bipolar disorder

Bipolar disorder is a serious psychiatric disorder with manic and depressive episodes. Psychosis, substance abuse, psychosocial disturbances and suicide are the most frequent consequences. Bipolar disorder has a high incidence, such as 1,5 to 4% in Caucasians. Twenty percent of the disease results in suicide, and because of untreated physical problems the life of patients is 30% shorter. In addition, this chronic disease bring important socio-economic burden to the individual, family and society. Although its genetic background is not solved yet, probably because of its multi factorial character, heritability chance predicted as 60-80%. Conclusion of the heritable character of the disease is followed by new approaches like; linkage analysis to detect candidate chromosomal locations and search for candidate genes in these locations. Results demonstrated that manic-depressive illness was caused by the combined effects of many genes plus environment. Understanding the underlying mechanisms and specifying genes has great importance in early detection and for new treatment strategies. The aim of this project is to search for mutations/polymorphisms in 5?upstrem and 3?UTR of GDNF (Glial Derived Neurotropic Factor) gene and calcium binding sites of MICU1 (Mitochondrial Calcium Uptake 1) gene that we suspect its involvement in this disease. For this study we collected blood samples to isolate DNAs from sixty six bipolar patients who were diagnosed according to DSM-V diagnostic criteria at the Psychiatry Clinic of Dokuz Eylul University Medical Faculty, twenty seven healthy relatives and fifty six healthy volunteers. Consequently this study demonstrated ten alterations GDNF genes 3 of them was new alterations. The SNP at the upstream of GDNF showed significantly difference between healthy group and patient group. Interestingly this difference was only between male groups. In this study no SNP found at calcium binding sites of MICU1 gene. Key words: Bipolar disorder, GDNF, MICU1, SNP