Genetic variants in nuclear-encoded mitochondrial proteins are associated with oxidative stress in obsessive compulsive disorders.

ABSTRACT

Obsessive compulsive disorder is a common psychiatric disorder defined by the presence of obsessive thoughts and repetitive compulsive actions. The mutations or polymorphic variants in mitochondrial DNA-encoded genes or nuclear genes result in oxidative stress, which has recently been associated with various psychiatric disorders. In order to understand the association of mitochondrial disorders with oxidative stress in obsessive compulsive disorder, we examined genetic variants of manganese superoxide dismutase and uncouple-2 antioxidant genes and malondialdehyde and glutathione, markers of oxidative stress. The study sample comprised 104 patients with OCD and 110 healthy controls. For manganese superoxide dismutase, the frequencies of CT (Ala/Val) genotype (p < 0.01) in patients were significantly lower than those of controls. In contrast, CC (Ala/Ala) genotype was significantly more frequent in patients than controls (p < 0.05). For uncouple-2 I/D, the frequencies of ID genotype (p < 0.01) and I allele (p < 0.05) were lower in patients as compared with controls. In contrast, DD genotype was more prevalent in patients than controls (p < 0.01). While whole blood glutathione was significantly diminished (p < 0.0001), serum malondialdehyde was significantly elevated in patients compared with controls (p < 0.0001). Malondialdehyde levels were significantly elevated in subjects with DD genotype of UCP-2 I/D (p < 0.05) and CC genotype of manganese superoxide dismutase (p < 0.05) as compared with II or ID and TT or CT genotype, respectively. Malondialdehyde levels in patients carrying CC (p < 0.05) or CT (p < 0.05) genotype were significantly higher than those of carrying TT genotype. In conclusion, CC genotype of manganese superoxide dismutase or DD genotype of UCP-2 might result in mitochondrial disorders by increasing oxidative stress in obsessive compulsive disorders.