| 1 | Biol. Psychiatry 2002 Nov 52: 847-54 |
|---|---|
| PMID | 12399137 |
| Title | Genome scan of three quantitative traits in schizophrenia pedigrees. |
| 抽象的 | Twin and adoption studies have consistently implicated genes in the etiology ofschizophrenia。分子遗传研究发现与基因组许多区域的联系一致。尽管这些令人鼓舞的结果，但这些发现均未达到全基因组的统计意义水平，并且没有一贯复制。 This report is a follow-up of a genome scan that analyzed linkage to the diagnosis ofschizophreniain a series of sibling pairs in the National Institute of Mental Health Genetics Initiative forschizophrenia数据。在这个报告中,我们使用相同的样本sess linkage to three quantitative traits developed from the Scale for the Assessment of Negative Symptoms and the Scale for the Assessment of Positive Symptoms: positive, negative, and disorganized symptoms. We show suggestive linkage to chromosomes 6, 9, and 20 for the disorganized trait and to chromosome 12 for the negative trait. We also show weak association withPAH（苯丙氨酸羟化酶）在该染色体上。 关于6染色体的发现复制了一些先前的发现，另一个基因座是新颖的。较大的样本将提供更多的功能来检测这种复杂疾病的连锁和关联。 |
| SCZ Keywords | schizophrenia, schizophrenic |
| 2 | 是。J. Med。基因。2002年8月114日：626-30 |
| PMID | 12210276 |
| Title | Aromatic amino acid hydroxylase genes and schizophrenia. |
| 抽象的 | 苯丙氨酸羟化酶（PAH), which catalyzes the conversion of phenylalanine to tyrosine, shares physical, structural and catalytic properties with tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH) that catalyze the rate-limiting steps in the biosynthesis of the neurotransmitters dopamine, noradrenaline, and serotonin. Because these neurotransmitter systems have all been implicated in the pathophysiology ofschizophrenia，芳香氨基酸羟化酶是与之相关的基因的候选者之一schizophrenia。A mutation in the functionally critical tetrahydrobiopterin cofactor binding domain of thePAHgene had been identified in African-American patients with the diagnosis ofschizophrenia, and biochemical analyses suggested that this mutation has physiological consequences related to amine neurotransmitter function. DNA sequencing of the highly conserved cofactor binding domain of thePAH, TH, and TPH genes in African-American subjects withschizophreniaand unrelated, never mentally ill subjects from the NIMHschizophreniaGenetics Initiative, was undertaken to assess the concordance of mutant genotype with psychiatric phenotype. The K274E mutation was observed in thePAH基因辅因子结合结构域和几种多态性在相邻的内含子区域中鉴定PAH，Th和TPH基因。观察到的所有遗传变异均表示schizophrenia小组和从未有精神疾病的小组。对受试者家庭成员的遗传评估PAHK274E mutation showed that all individuals with the K274E mutation also exhibited thePAHL321L多态性在催化结构域中PAHenzyme. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 3 | Biol. Psychiatry 2003 Mar 53: 543-53 |
| PMID | 12644360 |
| Title | Phenylalanine hydroxylase gene in psychiatric patients: screening and functional assay of mutations. |
| 抽象的 | Reports relating phenylalanine kinetics and metabolism to psychiatric disorders led us to undertake the comprehensive screening of the phenylalanine hydroxylase (PAH）在精神病患者和健康对照组样本中发现突变的编码区域和功能测试。 分析了来自精神病患者和对照组的基因组DNA，所有的序列变异PAH编码区域和接头连接。体内功能ional analysis of mutations was conducted by assessing the kinetics and conversion to tyrosine of a standardized phenylalanine dose and by measuring fasting pterin levels. A known missense mutation was observed in a schizoaffective subject, and a novel missense mutation was discovered in four subjects withschizophrenia还有一个正常的主题。对已知A403V突变的精神分裂症患者杂合子的杂合子显示，苯丙氨酸动力学的速率最低，并且患者样品中向酪氨酸的转化最低。四个schizophrenicpatients heterozygous for the novel K274E mutation showed significantly decreased phenylalanine kinetics, reduced conversion to tyrosine, and increased synthesis of thePAH辅因子四氢无生物翅目与schizophrenic没有突变的受试者。 The study findings suggest that larger scale studies are warranted to test the relationship of thePAHgenotype with a psychiatric phenotype. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 4 | Biol. Psychiatry 2003 Mar 53: 543-53 |
| PMID | 12644360 |
| Title | Phenylalanine hydroxylase gene in psychiatric patients: screening and functional assay of mutations. |
| 抽象的 | Reports relating phenylalanine kinetics and metabolism to psychiatric disorders led us to undertake the comprehensive screening of the phenylalanine hydroxylase (PAH）在精神病患者和健康对照组样本中发现突变的编码区域和功能测试。 分析了来自精神病患者和对照组的基因组DNA，所有的序列变异PAH编码区域和接头连接。体内功能ional analysis of mutations was conducted by assessing the kinetics and conversion to tyrosine of a standardized phenylalanine dose and by measuring fasting pterin levels. A known missense mutation was observed in a schizoaffective subject, and a novel missense mutation was discovered in four subjects withschizophrenia还有一个正常的主题。对已知A403V突变的精神分裂症患者杂合子的杂合子显示，苯丙氨酸动力学的速率最低，并且患者样品中向酪氨酸的转化最低。四个schizophrenicpatients heterozygous for the novel K274E mutation showed significantly decreased phenylalanine kinetics, reduced conversion to tyrosine, and increased synthesis of thePAH辅因子四氢无生物翅目与schizophrenic没有突变的受试者。 The study findings suggest that larger scale studies are warranted to test the relationship of thePAHgenotype with a psychiatric phenotype. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 5 | Hum. Genet. 2006 Aug 120: 22-30 |
| PMID | 16741719 |
| Title | Meta-analysis shows association between the tryptophan hydroxylase (TPH) gene and schizophrenia. |
| 抽象的 | A number of studies have suggested an association betweenschizophreniaand the tryptophan hydroxylase (TPH) and tyrosine hydroxylase (TH) genes. On the other hand, several studies attempting to replicate these findings have produced mixed results, possibly reflecting inadequate statistical power of the individual studies as well as the heterogeneity inherent inschizophrenia。为了阐明这种不一致的目的，我们的荟萃分析使用了截至2006年2月发表的多种研究方法将所有研究结合在一起，以全面了解三个羟化酶相关基因的作用。beplay苹果手机能用吗TPH A218C/A779C（OR = 1.18，95％C.I. C.I. 1.06-1.33，p = 0.004）显示与schizophrenia。但是，TH和苯丙氨酸羟化酶的证据（PAH）基因很弱。在当前的研究中未发现出版偏见。这些发现可能暗示TPH参与schizophrenia，具有潜在的重要临床，科学和公共卫生影响，并为研究与羟化酶相关的药物的研究提供了推定的基础。据我们所知，这是三个基因与schizophrenia。 |
| SCZ Keywords | schizophrenia, schizophrenic |
| 6 | 精神分裂。res。2009年4月109日：94-7 |
| PMID | 19268543 |
| Title | SLC6A4，PAH，GABRB3和MAOB的多态性以及精神病特征的修饰。 |
| 抽象的 | We tested four genes [phenylalanine hydroxylase (PAH），5-羟色胺转运蛋白（SLC6A4），单胺氧化酶B（MAOB）和γ-氨基丁酸A受体β-3亚基（GABRB3）]对五个影响schizophrenia症状因素：妄想，幻觉，躁狂，抑郁和负面症状。在爱尔兰高密度研究的90个家庭子集中schizophreniaFamilies, thePAH232bp microsatellite allele demonstrated significant association with the delusions factor using both QTDT (F=8.0, p=.031) and QPDTPHASE (chi-square=12.54, p=.028). Also, a significant association between the GABRB3 191 bp allele and the hallucinations factor was detected using QPDTPHASE (chi-square=15.51, p=.030), but not QTDT (chi-square=2.07, p=.560). |
| SCZ Keywords | schizophrenia, schizophrenic |
| 7 | 是。J. Med。基因。B Neuropsychiatr. Genet. 2009 Jun 150B: 560-9 |
| PMID | 18937293 |
| Title | Convergent patterns of association between phenylalanine hydroxylase variants and schizophrenia in four independent samples. |
| 抽象的 | 苯丙氨酸羟化酶中隐性突变（PAH）基因对苯基酮尿（PKU）的易饮食与饮食中的苯丙氨酸相结合。先前的研究表明PAH变化可能会赋予风险schizophrenia, but comprehensive follow-up has not been reported. We analyzed 15 commonPAH"tag" SNPs and three exonic variations that are rare in Caucasians but common in African-Americans among four independent samples (total n = 5,414). The samples included two US Caucasian cohorts (260 trios, 230 independent cases, 474 controls), Bulgarian families (659 trios), and an African-American sample (464 families, 401 controls). Analyses of both US Caucasian samples revealed associations with five SNPs; most notably the common allele (G) of rs1522305 from case-control analyses (z = 2.99, P = 0.006). This SNP was independently replicated in the Bulgarian cohort (z = 2.39, P = 0.015). A non-significant trend was also observed among African-American families (z = 1.39, P = 0.165), and combined analyses of all four samples were significant (rs1522305: chi(2) = 23.28, 8 d.f., P = 0.003). Results for rs1522305 met our a priori criteria for statistical significance, namely an association that was robust to multiple testing correction in one sample, a replicated risk allele in multiple samples, and combined analyses that were nominally significant. Case-control results in African-Americans detected an association with L321L (P = 0.047, OR = 1.46). Our analyses suggest several associations atPAH, with consistent evidence for rs1522305. Further analyses, including additional variations and environmental influences such as phenylalanine exposure are warranted. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 8 | 精神病学水库2012年7月198日：202-6 |
| PMID | 22414661 |
| Title | Investigating association of four gene regions (GABRB3, MAOB, PAH, and SLC6A4) with five symptoms in schizophrenia. |
| 抽象的 | Recently, microsatellite polymorphisms have been reported to be associated with four genes, GABRB3, MAOB,PAH，和SLC6A4及其关系已被测试到五个症状因素：幻觉，妄想，负面症状，躁狂和抑郁症。这些因素经常存在于schizophrenia爱尔兰高密度研究中的频谱障碍schizophrenia带有诊断的概率的家庭（ISHDSF）schizophrenia(Bergen et al., 2009). Of these, GABRB3 andPAHwere reported to be significantly associated with hallucinations and delusions in a 90-family subset of the ISHDSF, respectively. In this study, we tested the association of genetic markers from these four gene regions with the approximate five clinical symptoms, based upon 256schizophreniapatients, with genotypic data obtained by higher resolution single nucleotide polymorphism (SNP) genotyping. We found one GABRB3 SNP (rs1426891, 70.8kb downstream of this gene) and haplotype constructed by three SNPs (rs1426891, rs2912602, and rs2912600) were significantly associated with hallucinations in Caucasians after Bonferroni correction for multiple testing (Bonferroni corrected P: 0.032 and 0.016, respectively). Additionally, we found one haplotype constructed by two SNPs, rs5905587-rs37615860, in MAOB/NDP gene region was significantly associated with delusions in all samples tested (Bonferroni corrected P: 0.048). These results provide additional evidence that GABRB3 and MAOB/NDP gene regions might constitute risk factors for hallucinations and delusions inschizophrenia。 |
| SCZ Keywords | schizophrenia, schizophrenic |
| 9 | 拱。口服生物。2014年4月59日：363-9 |
| PMID | 24606907 |
| Title | PAH和LAT1中的普通变体与波兰人群中有或没有裂口的非合成裂唇唇（NSCL/P）的关联。 |
| 抽象的 | 有或没有裂口的非合成裂口（NSCL/P）是具有复杂且多因素病因的常见结构畸形。已经提出了苯丙氨酸代谢和口面裂口异常的关联。 Eight single nucleotide polymorphisms (SNPs) of genes encoding phenylalanine hydroxylase (PAH）和大型中性L-氨基酸转运蛋白1型（LAT1）以及PAHmutation that is most common in the Polish population (rs5030858; R408W), were investigated in 263 patients with NSCL/P and 270 matched controls using high resolution melting curve analysis (HRM). We found that two polymorphic variants ofPAHappear to be risk factors for NSCL/P. The odds ratio (OR) for individuals with the rs7485331 A allele (AC or AA) compared to CC homozygotes was 0.616 (95% confidence interval [CI]=0.437-0.868; p=0.005) and this association remains statistically significant after multiple testing correction. ThePAHrs12425434, previously associated withschizophrenia, was borderline associated with orofacial clefts. Moreover, haplotype analysis of polymorphisms in thePAH基因揭示了一种4标记的组合，与NSCL/p显着相关。由SNP RS74385331，RS12425434，RS1722392和突变RS5030858组成的单倍型的全局P值为0.032，但该关联在多次测试校正中无法幸存。 This study suggests the involvement of thePAHgene in the aetiology of NSCL/P in the tested population. Further replication will be required in separate cohorts to confirm the consistency of the observed association. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 10 | PLoS ONE 2014 -1 9: e85945 |
| PMID | 24465804 |
| Title | Elevated levels of plasma phenylalanine in schizophrenia: a guanosine triphosphate cyclohydrolase-1 metabolic pathway abnormality? |
| 抽象的 | 苯丙氨酸和酪氨酸是合成多巴胺所需的前体氨基酸，这是与神经生物学有关的主要神经递质schizophrenia。Inflammation, increasingly implicated inschizophrenia, can impair the function of the enzyme Phenylalanine hydroxylase (PAH;这会催化苯丙氨酸向酪氨酸的转化），从而导致苯丙氨酸水平升高并降低酪氨酸水平。这项研究旨在比较苯丙氨酸，酪氨酸及其比例（代理PAHfunction) in a relatively large sample ofschizophrenia患者和健康对照。 We measured non-fasting plasma phenylalanine and tyrosine in 950schizophreniapatients and 1000 healthy controls. We carried out multivariate analyses to compare log transformed phenylalanine, tyrosine, and phenylalanine:tyrosine ratio between patients and controls. Compared to controls,schizophreniapatients had higher phenylalanine (p<0.0001) and phenylalanine: tyrosine ratio (p<0.0001) but tyrosine did not differ between the two groups (p?=?0.596). 苯丙氨酸和苯丙氨酸升高：血液中的酪氨酸比率schizophreniapatients have to be replicated in longitudinal studies. The results may relate to an abnormalPAHfunction inschizophreniathat could become a target for novel preventative and interventional approaches. |
| SCZ Keywords | schizophrenia, schizophrenic |