Study On The Related Gene Of EOPD: MAO-B And COMT

Part One Study on the Relationship between Genetic Polymorphisms of MAO-B and Early-onset Parkinson's disease[Background]Parkinson's disease(PD)is a degenerative disorder of the central nervous system characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta and the decrease of dopamine content in the striatum.The pathogenesis of PD is unclear.Studies show that multiple mechanisms participate in the morbility process of PD,for example,oxidative stress,neuropoison susceptibility, toxic effects of excitatory amino acids,inflammation and immune factors,cell apoptosis,et al.Active views generally presume that the morbility of PD suffer from both environmental factors and genetic factors.Especially when genetic defects and environmental toxins coexist,the onset risk of PD could increase.But not all the persons who exposure to the same environmental factors appear symptoms of PD,which hints that individual hereditary predisposition also determines the occurrence of PD.In recent years,the patients of early-onset Parkinson's disease (EOPD,＜50 years)who have visited out-patient clinics of neuro-internal medicine in our hospital have increased,whose related hereditary genes have been discovered that distribute in different chromosomes,which proves that hereditary factors play an important role in EOPD.Now the study of hereditary predisposing genes in EOPD mainly concretrates on dopamine receptor gene systems.So a series of apoenzyme genes in DA become genetic investigative hot spots in EOPD genetics.The study of related genes in EOPD patients mainly concentrates on the exploration of hereditary predisposing genes,which is to say that the defect and mutation of this gene pose the enhancement of surrounding toxic sensitivity in carriers,so EOPD patients easily acquire PD in evoked conditions.Now men think highly of dopamine metabolic systematic genes(monoamine oxidase genes,catechol-O-methyltransferase genes, dopamine transporter genes,dopamine receptor genes,et al).The quantity and high or low activity of associated proteins in dopamine matebolic systems play an important role in process of pathophysiology originated from degrade of dopamine in EOPD.So it is necessary to make futher study in the correlation between the polymorphisms and mutations of genes coded theses proteins and EOPD. Monoamine Oxidase B(MAO-B)can activate MPTP,which is 1-methyl-4-phenyl-1, 2,3,6-tetrahydropyridine(MPTP)that induces nerve cell to death.MAO-B can form free radicle and hydrogen dioxide when it decomposes dopamine.MAO-B is expressed in substantia nigra.It is indicated lately by the study of abroad literatures that MAO-B is the absolutedly independent risk factor of EOPD.It may slow down the development of PD when the drugs of inhibiting MAO-B are utilized early in clinics.[Objectives]To approach the relationship between genotypes,alleles of MAO-B and EOPD.[Methods]Using PCR-RFLP,we study the distributional difference of frequency in genotypes and alleles of MAO-B among 65 EOPD groups,60 LOPD groups and 66 healthy controls(＜50 years).[Results]1.The frequency of A/A genotypes is higher in EOPD groups than in healthy controls,the difference between them is statistical significance(P＜0.05).2.The frequency of A/A genotypes between EOPD groups and LOPD groups, between LOPD groups and healthy controls have no statistical significance(P＞0.05).3.The frequency of A/A genotypes between male EOPD groups and male healthy controls,between female EOPD groups and female healthy controls have no statistical significance(P＞0.05).4.The frequency of A/A genotypes between male EOPD groups and male LOPD groups,between female EOPD groups and female LOPD groups have no statistical significance(P＞0.05).5.The frequency of A/A genotypes between male LOPD groups and male healthy controls,between female LOPD groups and female healthy controls have no statistical significance(P＞0.05).6.The frequency of A alleles is higher in EOPD groups than in healthy controls, the difference between them is statistical significance(P＜0.01).7.The frequency of A alleles between EOPD groups and LOPD groups,between LOPD groups and healthy controls have no statistical significance(P＞0.05).8.The frequency of A alleles is higher in male EOPD groups than in male healthy controls,the difference between them is statistical significance(P＜0.05);the frequency of A alleles is higher in female EOPD groups than in female healthy controls,the difference between them is statistical significance(P＜0.05). 9.The frequency of A alleles between male EOPD groups and male LOPD groups, between female EOPD groups and female LOPD groups have no statistical significance(P＞0.05).10.The frequency of A alleles between male LOPD groups and male healthy controls,between female LOPD groups and female healthy controls have no statistical significance(P＞0.05 and P=0.05).[Conclusions]The A/A genotypes of MAO-B are the risk factors of EOPD groups.The A alleles of MAO-B are the risk factors of EOPD groups,male EOPD groups and female EOPD groups.Part Two Study on the Relationship between Genetic Polymorphisms of COMT and Early-onset Parkinson's disease[Background]Parkinson's disease(PD)is a degenerative disorder of the central nervous system characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta and the decrease of dopamine content in the striatum.The pathogenesis of PD is unclear.Studies show that multiple mechanisms participate in the morbility process of PD,for example,oxidative stress,neuropoison susceptibility, toxic effects of excitatory amino acids,inflammation and immune factors,cell apoptosis,et al.Active views generally presume that the morbility of PD suffer from both environmental factors and genetic factors.Especially when genetic defects and environmental toxins coexist,the onset risk of PD could increase.But not all the persons who exposure to the same environmental factors appear symptoms of PD,which hints that individual hereditary predisposition also determines the occurrence of PD.In recent years,the patients of early-onset Parkinson's disease (EOPD,＜50 years)who have visited out-patient clinics of neuro-internal medicine in our hospital have increased,whose related hereditary genes have been discovered that distribute in different chromosomes,which proves that hereditary factors play an important role in EOPD.Now,the study of hereditary predisposing genes in EOPD mainly concretrates on dopamine receptor gene systems.So a series of apoenzyme genes in DA become genetic investigative hot spots in EOPD genetics.The study of related genes in EOPD patients mainly concentrates on the exploration of hereditary predisposing genes,which is to say that the defect and mutation of this gene pose the enhancement of surrounding toxic sensitivity in carriers,so EOPD patients easily acquire PD in evoked conditions.Now men think highly of dopamine metabolic systematic genes(monoamine oxidase genes,catechol-O-methyltransferase genes, dopamine transporter genes,dopamine receptor genes,et al).The quantity and high or low activity of associated proteins in dopamine matebolic systems play an important role in process of pathophysiology originated from degrade of dopamine in EOPD.So it is necessary to make futher study in the correlation between the polymorphisms and mutations of genes coded theses proteins and EOPD.Catechol-O-methyltransferase(COMT)catalyzes catecholamine to methylation to degradation,which possesses biological activity or toxicity of catecholamine's major metabolic enzymes.The effective substrates of COMT are catechol hormones and neurotransmitters,such as adrenaline,noradrenaline and dopamine etc.The degradation process is to catalyze methyl to transfer from S-adenosine-L-methionine to 3 position hydroxyl of catecholamines compounds by Mg²⁺,which can form methylated products.It has been indicated by research that the active alteration of COMT is related to Parkinson's disease and mental disorder.COMT genes of mankind locate in 22q11.1-q11 of somatic chromosome,whose 1947 position nucleotide exists G/A polymorphisms.It can pose amino acid mutation of Val158Met, which can alter the activity of COMT.The activity of Val(COMT-H)is three or four times of Val(COMT-L).Now the polymorphisms of COMT G/A have been used generally as a biological marker in the etiology and liability of nerve and mental disorders.[Objectives]To approach the relationship between genotypes,alleles of COMT and EOPD.[Methods]Using PCR-RFLP,we study the distributional difference of frequency in genotypes and alleles of COMT among 65 EOPD groups,60 LOPD groups and 66 healthy controls(＜50 years).[Results]1.The frequency of A/A genotypes is higher in EOPD groups that in healthy controls,the difference between them is statistical signifiquence(P＜0.05);the frequency of A/A genotypes between EOPD groups and LOPD groups has no statistical signifiquence(P＞0.05);the frequency of A/A genotypes is higher in LOPD groups than in healthy controls,the difference between them is statistical signifiquence(P＜0.01).2.The frequency of A/A genotypes is higher in male EOPD groups than in male healthy controls,the difference between them is statistical signifiquence(P＜0.05);the frequency of A/A genotypes between female EOPD groups and female healthy controls has no statistical signifiquence(P＞0.05).3.The frequency of A/A genotypes between male EOPD groups and male healthy controls has no statistical signifiquence(P＞0.05);The frequency of A/A genotypes between female EOPD groups and female healthy controls has no statistical signifiquence(P＞0.05).4.The frequency of A/A genotypes is higher in male LOPD groups than in male healthy controls,the difference between them is statistical signifiquence(P＜0.05);the frequency of A/A genotypes is higher in female LOPD groups than in female healthy controls,the difference between them is statistical signifiquence(P＜0.05).5.The frequency of A alleles is higher in EOPD groups than in healthy controls, the difference between them is statistical signifiquence(P＜0.01);the frequency of A alleles between EOPD groups and LOPD groups has no statistical signifiquence(P＞0.05);the frequency of A alleles is higher in LOPD groups than in healthy controls,the difference between them is statistical signifiquence(P＜0.01).6.The frequency of A alleles is higher in male EOPD groups than in male healthy controls,the difference between them is statistical signifiquence(P＜0.01),the frequency of A alleles is higher in female EOPD groups than in female healthy controls,the difference between them is statistical signifiquence(P＜0.05).7.The frequency of A alleles between male EOPD groups and male LOPD groups has no statistical signifiquence(P＞0.05),the frequency of A alleles between female EOPD groups and female LOPD groups has no statistical signifiquence (P＞0.05).8.The frequency of A alleles is higher in male LOPD groups than in male healthy controls,the difference between them is statistical signifiquence(P＜0.01);the frequency of A alleles is higher in female LOPD groups than in female healthy controls,the difference between them is statistical signifiquence(P＜0.01).[Conclusions]The A/A genotypes of COMT are the risk factors in EOPD groups,LOPD groups, male EOPD groups,male LOPD groups and female LOPD groups.The A alleles of COMT are the risk factors in EOPD groups,LOPD groups,male EOPD groups,female EOPD groups,male LOPD groups and female LOPD groups.