VNTR Polymorphism of the AS3MT Gene Modifies the Association of Age of Onset of Schizophrenia with Prenatal and Perinatal Hypoxia

The interaction of environmental factors and genetic predisposition factors can action not only the risk of developing schizophrenia but also its course and functional outcome. Hypoxia in the prenatal and perinatal period is an important environmental risk factor. It can lead to disruption of the brain development and nervous system in the fetus and newborn and, as a consequence, to the development of psychopathology at a later age. In turn, the VNTR polymorphism of the AS3MT (arsenite methyltransferase) gene plays an important role in regulating the expression of the unique AS3MTd2d3 isoform, which is a potential risk factor for the development of schizophrenia. In our work, we studied the effect of interaction between hypoxia and VNTR of AS3MT on one of the clinical characteristics of the disease—the age of onset of schizophrenia. The study included 520 patients with schizophrenia from the Russian population, including 170 people who had a history of hypoxia in the prenatal or perinatal period. It was found that women with a history of hypoxia and the V2/V2 genotype have an earlier age of disease onset associated with a poor prognosis of the disease.