雌激素代谢酶CYP17、COMT基因多态性与妊娠期肝内胆汁淤积症易感性的关系

目的探讨参与雌激素合成和代谢的CYP17和COMT基因多态性与成都地区妊娠期肝内胆汁淤积症（ICP）发病的关系。方法应用聚合酶链反应．限制性片段长度多态性（PCR—RFLP）技术,对100例ICP患者和100名正常对照孕妇CYPl7基因启动予区（T．C）多态和COMT基因外显子4密码子158（G—A）多态性进行分析。结果①两组均存在CYP17基因T．c多态,但两组基因型TF、TC、CC频率和等位基因T、c频率的比较差异均无统计学意义（P〉0．05）;②两组均存在COMT基因G．A多态,但两组基因型GG、GA、AA频率和等位基因G、A频率的比较差异均无统计学意义（P〉0．05）。结论CYP17和COMT基因单核苷酸多态性与成都地区ICP发病风险无相关性。     

PTPN22基因多态性与中国广东汉族人群RA发病的相关性研究

目的检测中国广东地区汉族人群中类风湿关节炎(RA)发病与蛋白酪氨酸磷酸酶非受体型22(PTPN22)基因Arg620Trp/1858C>T多态性的关系。方法采用PCR-RFLP技术分析了广东汉族人群中148例散发RA患者和150例健康对照者PTPN22 1858位点基因型。结果在中国广东地区汉族人群中PTPN22 1858位点仅存在等位基因C,与RA的发病无关。结论中国广东地区汉族人群中,PTPN22 Arg620Trp多态性与RA的发病无关;PTPN22基因可能存在其他多态性位点,需作进一步探讨。     

RAR‐related orphan receptor A: One gene with multiple functions related to migraine

AimsRAR‐related orphan receptor (RORA) involves in regulation of several biological processes including inflammation and circadian rhythm that probably are involved in migraine pathophysiology. In the current study, the association between RORA rs11639084 and rs4774388 variants and susceptibility to migraine were investigated in a sample of Iranian migraine patients for the first time.MethodsIn a case‐control study including 400 participants, 200 migraineurs and 200 healthy controls, genotyping of RORA rs4774388 and rs11639084 polymorphisms was performed using tetra‐primer amplification refractory mutation system–polymerase chain reaction (TP‐ARMS‐PCR).ResultsThe distribution of rs4774388 C/T and T/T genotypes differed significantly between the studied groups. Moreover, an association was observed between rs4774388 and migraine under the recessive mode of inheritance (P = 0.002; OR = 1.89.; CI = 1.25‐2.87). The distribution of rs11639084 alleles and genotypes was not significantly different between migraineurs and healthy controls.ConclusionCurrent results suggest RORA, as a molecular link, may explain inflammation and circadian rhythm dysfunction in migraine. Further studies in different ethnicities are required to confirm the function of RORA in migraine development.     

Response to Lithium in Bipolar Disorder: Clinical and Genetic Findings

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Validation de l’échelle d’évaluation du vécu de l’accouchement (QEVA) auprès d’une population française

BackgroundA woman's negative perception of her subjective childbirth experience can have consequences on the mother's psychological state and on early mother–baby relationships. To date, there is no validated tool in France allowing to evaluate childbirth experience in a multidimensional way. The aim of this study is to validate the Questionnaire Assessing the Childbirth Experience (QEVA) in a French sample of mothers. This tool was developed in a previous study where the authors combined 25 items into 6 dimensions: representations and expectations, sensory perceptions, feeling of control, perceived social support (medical staff and partner), emotions (positive and negative) and first moments with the baby.MethodsThe sample included 256 women recruited in a maternity ward. Sociodemographic and obstetric characteristics of our sample were compared to those of the French national perinatal survey. The structure of the QEVA with 17 items was explored by an exploratory structural equation modeling (ESEM). An analysis of the internal consistency was conducted on the sub-scores of the identified factors, and the concurrent validity was assessed with the Peri-traumatic Distress Inventory (PDI) through a correlation and its associated t-test.ResultsThe characteristics of our sample and those of the national perinatal survey do not differ on age, marital status, parity, cannabis use, infertility treatment, epidural and baby weight, in favour of the good representativeness of our sample. The study of the QEVA structure revealed a 4-dimensional structure. Analysis of the psychometric qualities showed a good internal consistency, with an observed alpha value ranging from 0.69 to 0.86. The QEVA also shows a good concurrent validity with the peri-traumatic distress scores (r = 0.51).ConclusionTo date, the QEVA is the first standardized tool allowing a multidimensional evaluation of the subjective experience of childbirth. It has been validated on a French population using an exploratory structural equation modeling. This tool, which is simple to use and well accepted by mothers, enables health professionals not only to screen mothers experiencing difficult childbirth and in need of support, but also to adapt health care according to the dimensions of the birth experience and its associated difficulties (emotions during the birth, interactions with health professionals, first moments with the baby, or post-partum emotions).     

The nature of the self: Neural analyses and heritability estimates of self‐evaluations in middle childhood

How neural correlates of self‐concept are influenced by environmental versus genetic factors is currently not fully understood. We investigated heritability estimates of behavioral and neural correlates of self‐concept in middle childhood since this phase is an important time window for taking on new social roles in academic and social contexts. To do so, a validated self‐concept fMRI task was applied in a twin sample of 345 participants aged between 7 and 9 years. In the self‐concept condition, participants were asked to indicate whether academic and social traits applied to them whereas the control condition required trait categorization. The self‐processing activation analyses (n = 234) revealed stronger medial prefrontal cortex (mPFC) activation for self than for control conditions. This effect was more pronounced for social‐self than academic self‐traits, whereas stronger dorsolateral prefrontal cortex (DLPFC) activation was observed for academic versus social self‐evaluations. Behavioral genetic modeling (166 complete twin pairs) revealed that 25–52% of the variation in academic self‐evaluations was explained by genetic factors, whereas 16–49% of the variation in social self‐evaluations was explained by shared environmental factors. Neural genetic modeling (91 complete twin pairs) for variation in mPFC and anterior prefrontal cortex (PFC) activation for academic self‐evaluations confirmed genetic and unique environmental influences, whereas anterior PFC activation for social self‐evaluations was additionally influenced by shared environmental influences. This indicates that environmental context possibly has a larger impact on the behavioral and neural correlates of social self‐concept at a young age. This is the first study demonstrating in a young twin sample that self‐concept depends on both genetic and environmental factors, depending on the specific domain.     

Parkin immunoreactivity in the brain of human and non-human primates: an immunohistochemical analysis in normal conditions and in Parkinsonian syndromes

The etiology of Parkinson's disease is unknown, but the gene involved in an autosomic recessive form of the disease with early onset has recently been identified. It codes for a protein with an unknown function called parkin. In the present study we produced a specific polyclonal antiserum against human parkin. Immunohistochemical analysis showed that parkin is expressed in neuronal perikarya and processes but also in glial and blood vessels in the primate brain (human and monkey). Electron microscopy indicated that parkin immunoreactivity is mostly located in large cytoplasmic vesicles and at the level of the endoplasmic reticulum. Parkin was expressed heterogeneously in various structures of the brain. It was detectable in the dopaminergic systems at the level of the perikarya in the mesencephalon but also in the striatum. However, parkin was also expressed by numerous nondopaminergic neurons. The staining intensity of parkin was particularly high in the hippocampal formation, the pallidal complex, the red nucleus, and the cerebellum. Comparison of control subjects with patients with Parkinson's disease and control animals with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-intoxicated animals revealed a loss of parkin-immunoreactive neurons only in the substantia nigra pars compacta. Furthermore, the surviving dopaminergic neurons in the parkinsonian state continued to express parkin at a level similar to that observed in the control situation. These data indicate that parkin is a widely expressed protein. Thus, the degeneration of dopaminergic neurons in familial cases of Parkinson's disease with autosomal recessive transmission cannot be explained solely in terms of an alteration of this protein.     

Neuregulin 1 genotype and schizophrenia

The neuregulin 1 (NRG1) gene has been the subject of considerable excitement within the psychiatric genetics literature since it was originally identified as a potential susceptibility locus for schizophrenia. Here we provide an update of our first meta-analysis of this association. Case-control and family-based genetic association studies of the NRG1 gene in healthy control groups and clinically diagnosed schizophrenia patients were included. We repeated the search strategy in our earlier meta-analysis for studies published between December 31, 2005, and September 30, 2007, and updated the results of our original meta-analysis accordingly. Superficially, the results of our updated meta-analysis are consistent with those in our previous report, although it is notable that the strength of evidence as based on our haplotype analysis has weakened over this period. The evidence for association of the SNP8NRG221533 polymorphism continued to be nonsignificant. We discuss a number of problems in the interpretation of a disparate and inconsistent gene-disease association literature, including the difficulties associated with determining what constitutes replication across studies which vary in their methods, marker sets employed, phenotype definition, and other study characteristics.     

Norepinephrine transporter and catecholamine-O-methyltransferase gene variants and attention-deficit/hyperactivity disorder symptoms in adults

Summary. Attention deficit/hyperactivity disorder (ADHD) is a complex, highly heritable psychiatric condition. Neuropsychological and pharmacological studies suggest a dysregulation of central noradrenergic neurotransmission in addition to dopaminergic and serotonergic mechanisms. Only a few studies have focused on the association of noradrenergic susceptibility genes with ADHD. In this study, we investigated the association of several ADHD symptom scores (German short form of the Wender Utah Rating Scale, WURS-k; ADHD self report, ADHD-SB, and the German validated version of the WRAADDS, WRI) with haplotypes of the catechol-O-methyltransferase (COMT) and the norepinephrine transporter (SLC6A2) genes. Subjects were genotyped for three SLC6A2 (rs5569, rs998424, rs2242447) and two COMT single nucleotide polymorphisms (rs4680, rs4818). In addition, psychosocial adversity in childhood was assessed in order to evaluate putative gene-environment interactions. We did not find main effects of the COMT and SLC6A2 NET1 gene haplotypes on any ADHD symptom severity score. Childhood psychosocial adversity was strongly associated with number of ADHD symptoms. No gene-environment interaction was found. A specific combination of two COMT and SLC6A2 gene haplotypes, containing the low functioning COMT variant was nominally associated with low ADHD scores in all scales. Results do not support the hypothesis that common variants in the SLC6A2 and COMT genes in particular are associated with ADHD, but might give some evidence for interactive effects between these gene variants on ADHD severity. Correspondence: Wolfgang Retz, Institute for Forensic Psychology and Psychiatry, Saarland University Hospital, 66421 Homburg/Saar, Germany