Dopaminergic and serotonergic genes in bipolar disorder: A case control study in a Sardinian population

SEVERINO, GIOVANNI;CONGIU, DONATELLA;MANCHIA, MIRKO;Chillotti C;Ardau R;DEL ZOMPO, MARIA

2006-01-01

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Abstract

Objectives: Several lines of evidence point to a role for dopamine and seroton in neurotransmission in mood disorders and in particular in Bipolar Disorder. We conducted a case-control study in order to investigate a possible association between the Bipolar Disorder using the: Ser9Gly variant in the D3 receptor gene (DRD3), 40-bp VNTR in the 30 untranslated region of the dopamine transporter gene (SLC6A3), the T102C polymorphism in 5-HT2A receptor gene (HTR2A), the Cys23Ser substitution in the 5-HT2C receptor gene (HTR2C) and the 5- HTTLPR polymorphism in the serotonin transporter gene (SLC6A4 ). Methods: We genotyped a sample of 300 unrelated Sardinian bipolar patients (BP) (110 males, 190 females) according to RDC and 277 healthy Sardinian control anonymous blood donors (133 males, 144 females). BP were recruited at the outpatients unit of the Section of Clinical Pharmacology, Department of Neuroscience, University of Cagliari. Lifetime consensus diagnoses were achieved using the SADSL and available medical records. The study was approved by the local Ethics Committee and informed written consent obtained from all subjects. Polymorphisms were analyzed by PCR. Statistical analysis was performed using Chi-square or Monte Carlo test. Results: BP consisted in 46 bipolar II, 180 bipolar I and 74 schizoaffective disorder bipolar types. We did not found any statistically significant difference in allele frequencies between BP and controls for all genes: DRD3 [p-value¼0.81; OR¼1.04 (95% CI 0.80- 1.33)]; SLC6A3 [p-value 0.34]; HTR2A [p-value 0.08, OR 1.23 (95% CI 0.97–1.55)]; HTR2C [p-value 0.45; OR 0.86 (95% CI 0.61–1.21)]; SLC6A4 [p-value 0.15; OR 1.19 (95% CI 0.94–1.50)]. Conclusion: Our preliminary analysis does not show any significant association between Bipolar Disorder and these candidate genes.