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
Polymorphisms in BDNF, AKT1, GSK3B genes: possible association with antipsychotic-induced hyperprolactinemia in schizophrenia patients
COMT gene polymorphism and antipsychotic-induced hyperprolactinemia in schizophrenia patients
Hyperprolactinemia (HPRL) is considered to be a frequent and typical adverse drug reaction caused by antipsychotic medications first and foremost due to excessive dopamine D2 receptors blockade. The aim is to study the set of polymorphisms of genes encoding neurotransmitter synthesis and metabolism enzymes COMT, TPH1 and TPH2 in schizophrenia inpatients. A comprehensive examination of 446 schizophrenia inpatients, aged 18-75 years, was conducted. Genotyping of DNA samples in patients with or without HPRL was carried out for 14 polymorphisms of COMT, TPH1, and TPH2 genes. We revealed an association between carriership of the COMT rs165774* G allele and HPRL. As a result of the study, a regression model was designed to predict the risk of developing HPRL in schizophrenia inpatients, taking into account age, gender, and treatment duration, the dosage of drugs in chlorpromazine equivalents as independent covariates and genotypes of the studied polymorphisms