Association of the COMT synonymous polymorphism Leu136Leu and missense variant Val158Met with mood disorders.


BACKGROUND:Major depressive disorder (MDD) and bipolar disorder (BD) are the two most common mood disorders. Given the recognized involvement of catecholamines in depression, genetic research focused on the evaluation of polymorphisms in genes coding for proteins that regulate neurotransmitter release, transport and degradation. Here we aimed at evaluating the distribution of two genetic variants of catechol-O-methyltransferase (COMT), namely the well characterized missense polymorphism G1947A (Val158Met) and the recently reported synonymous polymorphism C1886G (Leu136Leu), in MDD and BD patients compared with healthy subjects. METHODS:Genotyping for COMT polymorphisms was carried out by DNA direct sequencing in 112 patients (54 MDD and 58 BD) and 58 healthy subjects. RESULTS:We did not find significant differences in the Val158Met variant distribution between patients and controls. Instead, we found that the C1886 major allele and the CC1886 wild-type genotype frequencies were significantly higher in controls than in both groups of patients. On the contrary, the G1886 minor allele and the heterozygous CG1886 genotype were significantly more present in both MDD and BD patients than in healthy subjects. When looking at combined polymorphisms, we found a significantly higher frequency of the double heterozygous diplotype CG/GAVal/Met158 in both MDD and BD patients than in controls. Instead, the diplotype CC/GAVal/Met158 showed a significantly higher frequency in controls than in BD patients. LIMITATIONS:The small size of our study cohort may limit the generalizability of the present findings. CONCLUSIONS:This work first showed the association of combined Leu136Leu and Val158Met variants of COMT gene with MDD and BD.


J Affect Disord


Pandolfo G,Gugliandolo A,Gangemi C,Arrigo R,Currò M,La Ciura G,Muscatello MR,Bruno A,Zoccali R,Caccamo D




Has Abstract


2015-05-15 00:00:00












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