Contribution of xenobiotic detoxication genes in the risk of affective disorder

  • Н. Н. Левкович State Institute of Genetic and Regenerative Medicine National Academy of Medical Sciences of Ukraine Ukraine, 04114, Kyiv, Vyshhorodska Str., 67
  • Н. Г. Горовенко P.L.Shupik National medical academy of post-graduate education 9 Ukraine, 04112, Kyiv, Dorohozhytska St., 9

Abstract

Aim. The aim was to evaluate contribution of G1934A, G681A, C430T, A1075C and C3435T polymorphic variants of CYP2D6, CYP2C19, CYP2C9 and MDR1 genes in the risk of affective disorders development. Methods. 144 patients with affective disorders and 106 healthy control subjects were genotyped for major polymorphic variants of xenobiotic detoxication genes. Genotyping was performed using allele-specific polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Results. Presence of 3435TT genotype of MDR1 gene was found to increase twice the affective disorders risk, while 3435C allele in homo- or heterozygous condition has a protective effect. The analysis of genotype combinations by the studied polymorphic variants of CYP2C9, CYP2C19, CYP2D6 and MDR1 genes has been carried out. It is proved that a significant contribution to the risk of AD made patients with debut of disease prior to 25 years. Conclusions. It was determined that to predict risk of AD development, the most informative among others investigated may be С3435T polymorphic variant of MDR1 gene. The 3435TT genotype by C3435T polymorphic variant of MDR1 gene contributes greatly to the risk of AD, and in combination with other allelic variants of genes encoding enzymes of xenobiotic detoxication, this risk increases statistically significantly. The 3435CT genotype shows a protective effect in the affective disorders risk.

Keywords: polymorphism, affective disorders, detoxication.