8 research outputs found
ΠΡΡΠΎΡΠΈΠ°ΡΠΈΡ ΠΏΠΎΠ»ΠΈΠΌΠΎΡΡΠ½ΡΡ Π²Π°ΡΠΈΠ°Π½ΡΠΎΠ² Π³Π΅Π½Π° ΠΌΠΎΠ·Π³ΠΎΠ²ΠΎΠ³ΠΎ Π½Π΅ΠΉΡΠΎΡΡΠΎΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΡΠ°ΠΊΡΠΎΡΠ° (BDNF rs6265) ΠΈ Π³Π΅Π½Π° ΠΏΠ΅ΡΠ΅Π½ΠΎΡΡΠΈΠΊΠ° Π³Π»ΡΡΠ°ΠΌΠ°ΡΠ° Π²ΡΠΎΡΠΎΠ³ΠΎ ΡΠΈΠΏΠ° (SLC1A2 rs4354668) Ρ ΡΠ΅ΡΠ΅Π½ΠΈΠ΅ΠΌ ΡΠ°ΡΡΠ΅ΡΠ½Π½ΠΎΠ³ΠΎ ΡΠΊΠ»Π΅ΡΠΎΠ·Π° Ρ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ², ΠΏΡΠΎΠΆΠΈΠ²Π°ΡΡΠΈΡ Π² Π’ΠΎΠΌΡΠΊΠΎΠΉ ΠΎΠ±Π»Π°ΡΡΠΈ
Background: Multiple sclerosis (MS) is an autoimmune disease of the central nervous system that affects people of working age and ultimately leads to disability. This disease is of polygenic origin. The role of factors related to the pathogenesis of the disease and affecting both neuroinflammation and remyelination is studied. Aims: Our goal was to investigate the association of single nucleotide polymorphisms BDNF rs6265 and SLC1A2 rs4354668 with the risk of occurrence, clinical manifestations and the course of MS.Materials and methods: The study included 302 patients with MS, 268 healthy volunteers were enrolled in a control group. The obtained blood was used for DNA extraction by standard phenol-chloroform method. The identification of allelic variants of genes SLC1A2 (rs4354668) and BDNF (rs6265) was performed by polymerase chain reaction.Results: When comparing the frequencies of genotypes and alleles of polymorphic variants of BDNF and SLC1A2 genes between the groups of MS patients and the control group, no statistically significant differences were revealed. Comparison of genotype and allele frequencies of patients depending on sex, age of onset of the disease also did not reveal statistically significant differences. The study of the association of polymorphic variant of the gene BDNF (rs6265) with clinical manifestations of the disease revealed the association of genotype CC with oculomotor and trigeminal disorders at the onset of the disease (F=7, p=0.017). The study of the polymorphic variant rs4354668 of the glutamate transporter gene SLC1A2 revealed the association of allele G with an earlier (within 5 years from the moment of debut) transition of the disease to the stage of secondary progression, despite the therapy with DMT (Ο2=5.940; p=0.010; OR 1.58; 95% CI 1.09β2.29). Homozygous genotype of TT (Ο2=6.393; p=0.041; OR 0.50; 95% CI 0.28β0.88) and allele T (Ο2=5.940; p=0.010; OR 0.63; 95% CI 0.44β0.92) of the polymorphism rs4354668 of the glutamate transporter gene SLC1A2 are significantly more common in the group of patients with late transition (15 years or more from the moment of debut) to the secondary progressive course.Conclusions: In our study we revealed the relationship of the studied polymorphic variants of genes with clinical signs at the onset of the disease and with the clinical manifestations of MS in patients living in the Tomsk region.ΠΠ±ΠΎΡΠ½ΠΎΠ²Π°Π½ΠΈΠ΅. Π Π°ΡΡΠ΅ΡΠ½Π½ΡΠΉ ΡΠΊΠ»Π΅ΡΠΎΠ· β Π°ΡΡΠΎΠΈΠΌΠΌΡΠ½Π½ΠΎΠ΅ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠ΅ Π½Π΅ΡΠ²Π½ΠΎΠΉ ΡΠΈΡΡΠ΅ΠΌΡ, ΠΏΠΎΡΠ°ΠΆΠ°ΡΡΠ΅Π΅ Π»ΡΠ΄Π΅ΠΉ ΡΡΡΠ΄ΠΎΡΠΏΠΎΡΠΎΠ±Π½ΠΎΠ³ΠΎ Π²ΠΎΠ·ΡΠ°ΡΡΠ° ΠΈ ΠΏΡΠΈΠ²ΠΎΠ΄ΡΡΠ΅Π΅ Π² ΠΊΠΎΠ½Π΅ΡΠ½ΠΎΠΌ ΠΈΡΠΎΠ³Π΅ ΠΊ ΠΈΠ½Π²Π°Π»ΠΈΠ΄ΠΈΠ·Π°ΡΠΈΠΈ. Π ΠΏΠΎΡΠ»Π΅Π΄Π½ΠΈΠ΅ Π³ΠΎΠ΄Ρ Π½Π°Π±Π»ΡΠ΄Π°Π΅ΡΡΡ ΡΠΎΡΡ ΡΠΈΡΠ»Π° Π±ΠΎΠ»ΡΠ½ΡΡ
, ΡΠ²ΡΠ·Π°Π½Π½ΡΠΉ ΠΊΠ°ΠΊ Ρ ΠΈΡΡΠΈΠ½Π½ΡΠΌ ΡΠ²Π΅Π»ΠΈΡΠ΅Π½ΠΈΠ΅ΠΌ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π΅ΠΌΠΎΡΡΠΈ, ΡΠ°ΠΊ ΠΈ Ρ ΠΊΠ°ΡΠ΅ΡΡΠ²ΠΎΠΌ Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΠΊΠΈ.Π¦Π΅Π»Ρ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ β ΠΎΡΠ΅Π½ΠΊΠ° Π°ΡΡΠΎΡΠΈΠ°ΡΠΈΠΈ ΠΎΠ΄Π½ΠΎΠ½ΡΠΊΠ»Π΅ΠΎΡΠΈΠ΄Π½ΡΡ
ΠΏΠΎΠ»ΠΈΠΌΠΎΡΡΠ½ΡΡ
Π²Π°ΡΠΈΠ°Π½ΡΠΎΠ² Π³Π΅Π½ΠΎΠ² BDNF rs6265 ΠΈ SLC1A2 rs4354668 Ρ ΡΠΈΡΠΊΠΎΠΌ Π²ΠΎΠ·Π½ΠΈΠΊΠ½ΠΎΠ²Π΅Π½ΠΈΡ, ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΠΌΠΈ ΠΏΡΠΎΡΠ²Π»Π΅Π½ΠΈΡΠΌΠΈ ΠΈ ΡΠ΅ΡΠ΅Π½ΠΈΠ΅ΠΌ ΡΠ°ΡΡΠ΅ΡΠ½Π½ΠΎΠ³ΠΎ ΡΠΊΠ»Π΅ΡΠΎΠ·Π°.ΠΠ΅ΡΠΎΠ΄Ρ. Π ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅ Π±ΡΠ»ΠΎ Π²ΠΊΠ»ΡΡΠ΅Π½ΠΎ 302 ΠΏΠ°ΡΠΈΠ΅Π½ΡΠ° Ρ ΡΠ°ΡΡΠ΅ΡΠ½Π½ΡΠΌ ΡΠΊΠ»Π΅ΡΠΎΠ·ΠΎΠΌ, 268 Π·Π΄ΠΎΡΠΎΠ²ΡΡ
Π΄ΠΎΠ±ΡΠΎΠ²ΠΎΠ»ΡΡΠ΅Π² ΡΠΎΡΡΠ°Π²ΠΈΠ»ΠΈ Π³ΡΡΠΏΠΏΡ ΠΊΠΎΠ½ΡΡΠΎΠ»Ρ. ΠΠ°ΡΠΈΠ΅Π½ΡΡ Π½Π°Ρ
ΠΎΠ΄ΠΈΠ»ΠΈΡΡ Π½Π° Π»Π΅ΡΠ΅Π½ΠΈΠΈ Π² Π½Π΅Π²ΡΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΎΠΉ ΠΊΠ»ΠΈΠ½ΠΈΠΊΠ΅ Π‘ΠΈΠ±ΠΈΡΡΠΊΠΎΠ³ΠΎ Π³ΠΎΡΡΠ΄Π°ΡΡΡΠ²Π΅Π½Π½ΠΎΠ³ΠΎ ΠΌΠ΅Π΄ΠΈΡΠΈΠ½ΡΠΊΠΎΠ³ΠΎ ΡΠ½ΠΈΠ²Π΅ΡΡΠΈΡΠ΅ΡΠ°. ΠΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΈΠ΅ Π°Π»Π»Π΅Π»ΡΠ½ΡΡ
Π²Π°ΡΠΈΠ°Π½ΡΠΎΠ² Π³Π΅Π½ΠΎΠ² SLC1A2 (rs4354668) ΠΈ BDNF (rs6265) ΠΏΡΠΎΠ²ΠΎΠ΄ΠΈΠ»ΠΈ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ ΠΏΠΎΠ»ΠΈΠΌΠ΅ΡΠ°Π·Π½ΠΎΠΉ ΡΠ΅ΠΏΠ½ΠΎΠΉ ΡΠ΅Π°ΠΊΡΠΈΠΈ. ΠΠΌΠΏΠ»ΠΈΡΠΈΠΊΠ°ΡΠΈΡ ΠΈ Π°Π½Π°Π»ΠΈΠ· ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΠΎΠ² ΠΎΡΡΡΠ΅ΡΡΠ²Π»ΡΠ»ΠΈ Ρ ΠΏΠΎΠΌΠΎΡΡΡ ΠΏΡΠΈΠ±ΠΎΡΠΎΠ² StepOnePlus ΠΈ Quant Studio 5 (Applied Biosystems, Π‘Π¨Π).Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ. ΠΡΠΈ ΡΡΠ°Π²Π½Π΅Π½ΠΈΠΈ ΡΠ°ΡΡΠΎΡΡ Π³Π΅Π½ΠΎΡΠΈΠΏΠΎΠ² ΠΈ Π°Π»Π»Π΅Π»Π΅ΠΉ ΠΏΠΎΠ»ΠΈΠΌΠΎΡΡΠ½ΡΡ
Π²Π°ΡΠΈΠ°Π½ΡΠΎΠ² Π³Π΅Π½ΠΎΠ² BDNF ΠΈ SLC1A2 ΠΌΠ΅ΠΆΠ΄Ρ Π³ΡΡΠΏΠΏΠ°ΠΌΠΈ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Ρ ΡΠ°ΡΡΠ΅ΡΠ½Π½ΡΠΌ ΡΠΊΠ»Π΅ΡΠΎΠ·ΠΎΠΌ ΠΈ Π³ΡΡΠΏΠΏΠΎΠΉ ΠΊΠΎΠ½ΡΡΠΎΠ»Ρ ΡΡΠ°ΡΠΈΡΡΠΈΡΠ΅ΡΠΊΠΈ Π·Π½Π°ΡΠΈΠΌΡΡ
ΡΠ°Π·Π»ΠΈΡΠΈΠΉ Π½Π΅ Π²ΡΡΠ²Π»Π΅Π½ΠΎ. Π‘ΡΠ°Π²Π½Π΅Π½ΠΈΠ΅ ΡΠ°ΡΡΠΎΡΡ Π³Π΅Π½ΠΎΡΠΈΠΏΠΎΠ² ΠΈ Π°Π»Π»Π΅Π»Π΅ΠΉ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Π² Π·Π°Π²ΠΈΡΠΈΠΌΠΎΡΡΠΈ ΠΎΡ ΠΏΠΎΠ»Π°, Π²ΠΎΠ·ΡΠ°ΡΡΠ° Π½Π°ΡΠ°Π»Π° Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡ ΡΠ°ΠΊΠΆΠ΅ ΡΡΠ°ΡΠΈΡΡΠΈΡΠ΅ΡΠΊΠΈ Π·Π½Π°ΡΠΈΠΌΡΡ
ΡΠ°Π·Π»ΠΈΡΠΈΠΉ Π½Π΅ Π²ΡΡΠ²ΠΈΠ»ΠΎ. ΠΡΠΈ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΈ ΡΠ²ΡΠ·ΠΈ ΠΏΠΎΠ»ΠΈΠΌΠΎΡΡΠ½ΠΎΠ³ΠΎ Π²Π°ΡΠΈΠ°Π½ΡΠ° Π³Π΅Π½Π° BDNF (rs6265) Ρ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΠΌΠΈ ΠΏΡΠΎΡΠ²Π»Π΅Π½ΠΈΡΠΌΠΈ Π±ΠΎΠ»Π΅Π·Π½ΠΈ Π½Π°ΠΉΠ΄Π΅Π½Π° Π°ΡΡΠΎΡΠΈΠ°ΡΠΈΡ Π³Π΅Π½ΠΎΡΠΈΠΏΠ° Π‘Π‘ Ρ Π³Π»Π°Π·ΠΎΠ΄Π²ΠΈΠ³Π°ΡΠ΅Π»ΡΠ½ΡΠΌΠΈ ΠΈ ΡΡΠΈΠ³Π΅ΠΌΠΈΠ½Π°Π»ΡΠ½ΡΠΌΠΈ ΡΠ°ΡΡΡΡΠΎΠΉΡΡΠ²Π°ΠΌΠΈ Π² Π΄Π΅Π±ΡΡΠ΅ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡ (F=7; p=0,017). ΠΡΠΈ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΈ ΠΏΠΎΠ»ΠΈΠΌΠΎΡΡΠ½ΠΎΠ³ΠΎ Π²Π°ΡΠΈΠ°Π½ΡΠ° rs4354668 Π³Π΅Π½Π° Π³Π»ΡΡΠ°ΠΌΠ°ΡΠ½ΠΎΠ³ΠΎ ΡΡΠ°Π½ΡΠΏΠΎΡΡΠ΅ΡΠ° SLC1A2 Π²ΡΡΠ²Π»Π΅Π½Π° Π°ΡΡΠΎΡΠΈΠ°ΡΠΈΡ Π°Π»Π»Π΅Π»Ρ G Ρ Π±ΠΎΠ»Π΅Π΅ ΡΠ°Π½Π½ΠΈΠΌ (Π² ΡΠ΅ΡΠ΅Π½ΠΈΠ΅ 5 Π»Π΅Ρ ΠΎΡ ΠΌΠΎΠΌΠ΅Π½ΡΠ° Π΄Π΅Π±ΡΡΠ°) ΠΏΠ΅ΡΠ΅Ρ
ΠΎΠ΄ΠΎΠΌ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡ Π² ΡΡΠ°Π΄ΠΈΡ Π²ΡΠΎΡΠΈΡΠ½ΠΎΠ³ΠΎ ΠΏΡΠΎΠ³ΡΠ΅ΡΡΠΈΡΠΎΠ²Π°Π½ΠΈΡ, Π½Π΅ΡΠΌΠΎΡΡΡ Π½Π° ΡΠ΅ΡΠ°ΠΏΠΈΡ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠ°ΠΌΠΈ, ΠΈΠ·ΠΌΠ΅Π½ΡΡΡΠΈΠΌΠΈ ΡΠ΅ΡΠ΅Π½ΠΈΠ΅ ΡΠ°ΡΡΠ΅ΡΠ½Π½ΠΎΠ³ΠΎ ΡΠΊΠ»Π΅ΡΠΎΠ·Π° (Ο2=5,940; Ρ=0,010; OR 1,58; 95% CI 1,09β2,29). ΠΠΎΠΌΠΎΠ·ΠΈΠ³ΠΎΡΠ½ΡΠΉ Π³Π΅Π½ΠΎΡΠΈΠΏ Π’Π’ (Ο2=6,393; Ρ=0,041; OR 0,50; 95% CI 0,28β0,88) ΠΈ Π°Π»Π»Π΅Π»Ρ Π’ (Ο2=5,940; Ρ=0,010; OR 0,63; 95% CI 0,44β0,92) ΠΏΠΎΠ»ΠΈΠΌΠΎΡΡΠΈΠ·ΠΌΠ° rs4354668 Π³Π΅Π½Π° Π³Π»ΡΡΠ°ΠΌΠ°ΡΠ½ΠΎΠ³ΠΎ ΡΡΠ°Π½ΡΠΏΠΎΡΡΠ΅ΡΠ° SLC1A2 ΡΡΠ°ΡΠΈΡΡΠΈΡΠ΅ΡΠΊΠΈ Π·Π½Π°ΡΠΈΠΌΠΎ ΡΠ°ΡΠ΅ Π²ΡΡΡΠ΅ΡΠ°ΡΡΡΡ Π² Π³ΡΡΠΏΠΏΠ΅ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Ρ ΠΏΠΎΠ·Π΄Π½ΠΈΠΌ ΠΏΠ΅ΡΠ΅Ρ
ΠΎΠ΄ΠΎΠΌ (ΡΠ΅ΡΠ΅Π· 15 ΠΈ Π±ΠΎΠ»Π΅Π΅ Π»Π΅Ρ ΠΎΡ ΠΌΠΎΠΌΠ΅Π½ΡΠ° Π΄Π΅Π±ΡΡΠ°) Π²ΠΎ Π²ΡΠΎΡΠΈΡΠ½ΠΎ-ΠΏΡΠΎΠ³ΡΠ΅ΡΡΠΈΡΡΡΡΠ΅Π΅ ΡΠ΅ΡΠ΅Π½ΠΈΠ΅.ΠΠ°ΠΊΠ»ΡΡΠ΅Π½ΠΈΠ΅. Π Π½Π°ΡΠ΅ΠΌ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΈ Π²ΡΡΠ²Π»Π΅Π½Π° ΡΠ²ΡΠ·Ρ ΠΈΠ·ΡΡΠ°Π΅ΠΌΡΡ
ΠΏΠΎΠ»ΠΈΠΌΠΎΡΡΠ½ΡΡ
Π²Π°ΡΠΈΠ°Π½ΡΠΎΠ² Π³Π΅Π½ΠΎΠ² Ρ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΠΌΠΈ ΠΏΡΠΈΠ·Π½Π°ΠΊΠ°ΠΌΠΈ Π² Π΄Π΅Π±ΡΡΠ΅ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡ ΠΈ Ρ ΠΎΡΠΎΠ±Π΅Π½Π½ΠΎΡΡΡΡ ΡΠ΅ΡΠ΅Π½ΠΈΡ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡ Ρ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ², ΠΏΡΠΎΠΆΠΈΠ²Π°ΡΡΠΈΡ
Π½Π° ΡΠ΅ΡΡΠΈΡΠΎΡΠΈΠΈ Π’ΠΎΠΌΡΠΊΠΎΠΉ ΠΎΠ±Π»Π°ΡΡΠΈ
Gene polymorphism of serotonin receptors and drug-induced hyperprolactinemia in schizophrenic patients
CYP2D6 and catechol-O-methyltransferase gene polymorphisms in Parkinson patients with levodopa-induced dyskinesias
Parkinson's disease (PD), a common neurodegenerative disorder caused by the loss of the dopaminergic input to the basal ganglia, is commonly treated with levodopa (L-DOPA). Use of this drug, however, is severely limited by the development of side effect. Levodopa-induced dyskinesias (LID) are involuntary muscle movements that occur as a consequence of chronic levodopa (L-DOPA) treatment. LID are a substantial barrier to effective symptomatic management of Parkinson's disease (PD), up to 45% of L-DOPA users develop LID within 5 years [1]. Clinical heterogeneity of LID suggests a significant role of endogenous factors in determining their prevalence. Some evidence suggest a relationship between LID and specific genetic changes, such as changes in the genes controlling enzymes responsible for drug and monoamine metabolism, neurotransmitter receptors and proteins involved in oxidative stress or antioxidant function [2-4]. Objective: To investigate contribution of polymorphic variants of CYP2D6 and COMT genes in the development of LID in PD patients. Methods: 212 patients with Parkinson's disease on levodopa therapy were investigated. Dyskinesias were estimated with use of Abnormal Involuntary Movement Scale (AIMS). DNA extraction and fluorogenic 5'-exonuclease TaqMan genotyping assays were conducted according to standard protocols and blind to the clinical status of the subjects. Genotyping was carried out on 2 SNPs of CYP2D6 (CYP2D6β3, rs35742686; CYP2D6β4, rs3892097) and 7 SNPs of COMT genes (rs4680, rs6269, rs4633, rs4818, rs769224, rs165774, rs174696). The SPSS software was used for statistical analysis. Results: Patients in our cohort demonstrated typical PD demographics, with a mean age of onset of 60.04Β±9.46 years, a mean disease duration of 9.79Β±5.57 years. Dyskinesias were reported in 57 (26.9%) patients. The distribution of genotypes of studied genes corresponded to the Hardy-Weinberg equilibrium. Association of polymorphisms in CYP2D6 gene with side effects was not revealed. We found that rs4680 polymorphism in COMT gene is significantly associated with LID (Ο2 = 6.048, p = 0.049). Odds ratio for carriers of the genotype AA is 2.14 [95% CI: 1.11- 4.11], which indicates the predisposing effect of this genotype on the development of dyskinesias. Rs4680 is a functional SNP in genes encoding the catechol-O-methyltransferase enzyme, which catabolizes dopamine. A valine to methionine substitution at codon 158 of the COMT gene produces a Met variant that catabolizes dopamine up to four times slower than its Val counterpart. Conclusions: Polymorphisms in the COMT gene play significant role in the therapy response to L-DOPA as well as in various adverse effects. COMT is an extracellular enzyme which inactive variants increase the extracellular concentration of dopamine. This may increase the uptake of dopamine by indirect pathway MSN and therefore increase oxidative stress. We hypothesized that functional single nucleotide polymorphism rs4680 in COMT gene may result in a clinical phenotype contributing to an increased risk of LID. Thus, the polymorphism of gene possessing predisposing effects in development of levodopa induced dyskinesia in PD has been revealed that would allow predicting risk of development of movement disorders
CYP2D6 and catechol-O-methyltransferase gene polymorphisms in Parkinson patients with levodopa-induced dyskinesias
Association between P-glycoprotein polymorphisms and antipsychotic drug-induced hyperprolactinemia
Background: Regular therapy for schizophrenia includes maintenance antipsychotic treatment. Unfortunately, antipsychotics also have a spectrum of side effects, including metabolic, endocrine, cardiovascular, and movement disorders. One of the common side effects of these drugs is hyperprolactinemia (HPRL) [1]. This side effect is attributed to blockade of dopamine D2 receptors on the membranes of lactotroph cells within the pituitary gland. Certain antipsychotic drugs, e.g. risperidone, are more likely to induce HPRL because of relative accumulation within the adenohypophysis. The strong prolactin-elevating effect of risperidone reflects its relatively high blood/brain concentration ratio, a consequence of it being a substrate for the p-glycoprotein (P-gp, also known as ABCB1) pump [2]. Therefore, P-gp genotypes with altered functional activity might influence the potential of risperidone to cause HPRL as the changed blood/brain concentration ratio would lead to an altered vulnerability for CNS side effects like parkinsonism. Such side effects are expected to make dose adaptations necessary, which would also decrease exposure of lactrotroph dopamine D2 receptors. Aims: The present study aimed to investigate the influence of polymorphisms of the P-glycoprotein gene (ABCB1 gene) on the prevalence of antipsychotic-induced hyperprolactinemia in patients with schizophrenia. Methods: We studied the association between polymorphisms of the P-gp gene (ABCB1 gene) and antipsychotic drug-induced hyperprolactinemia in patients with schizophrenia from Siberia. Evaluation of serum prolactin was performed by ELISA using reagents set PRL Test System (USA). Genotyping was carried out on 8 polymorphic variants of the P-glycoprotein gene (rs1045642, rs2032582, rs4148739, rs28401781, rs2235040, rs9282564, rs2235015, and rs2032583). Associations between HPRL and polymorphisms of P-gp gene were established using logistic regression accounting for covariates (age, sex, duration of the disease, and CPZeq). An additive genetic model was tested and the analysis was carried out both in the total sample and in subgroups stratified by the use of risperidone/paliperidone (N = 76) or sulpiride/amisulpride (N = 13). Bonferroni correction was applied assuming 5 independent tests estimated via the correlation between the SNPs. Results: 446 Russian patients with schizophrenia were examined, including 225 women and 221 men [3]. The average age of patients was 42.1 Β± 1.4 years. No statistically significant associations were obtained in the total sample after correction for multiple-testing. However, the rs2032582 variant appeared to be protective against HPRL in the subgroup of patients using risperidone or paliperidone (OR = 0.17, 95% CI = 0.04β0.79, adjusted p = 0.041). Discussion: Our finding supports the hypothesis that a variant of P-gp gene may influence the likelihood of inducing HPRL in patients using risperidone or paliperidone (i.e. 9-hydroxy-risperidone). This may be related to affecting the blood/brain concentration ratio of the risperidone moiety. In the total sample the association was significant but did not survive correction for multiple testing. Moreover, another variant, rs4148739, was associated to a larger extent than rs2032582. Hence, the variant may affect the affinity of the risperidone moiety specifically without having consequences for the binding and transport of other antipsychotic drugs. Conclusion: Rs2032582 of the P-gp is negatively associated with risperidone/paliperidone-induced HPRL, but not with HPRL induced by other antipsychotic drugs. References [1] Peuskens, J., Pani, L., Detraux, J., De Hert, M., 2014. The effects of novel and newly approved antipsychotics on serum prolactin levels: a comprehensive review. CNS Drugs 28, 421β453. [2] Ejsing, T., Pedersen, A., Linnet, K., 2005. P-glycoprotein interaction with risperidone and 9-OH-risperidone studied in vitro, in knock-out mice and in drug-drug interaction experiments. Hum Psychopharmacol 20, 493β500. [3] Ivanova, S.A., Osmanova, D.Z., Freidin, M.B., Fedorenko, O.Y., Boiko, A.S., Pozhidaev, I.V., Semke, A.V., Bokhan, N.A., Agarkov, A.A., Wilffert, B., Loonen, A.J.M., 2017. Identification of 5-hydroxytryptamine receptor gene polymorphisms modulating hyperprolactinaemia in antipsychotic drug-treated patients with schizophrenia. World J Biol Psychiatry 18, 239β246. Keywords: Schizophrenia: clinical Pharmacokinetics Neuroendocrinolog