[Parameter optimization for non-contrast-enhanced selective magnetic resonance portography imaging].

OBJECTIVE: To evaluate subtraction images acquired with 3D true steady-state free-precession(SSFP)sequence combined with time-spatial labeling inversion pulse(T-SLIP)for selective and non-contrast-enhanced(non-CE)visualization of the portal venous system,and explore the optimization of this protocol. METHODS: Totally 13 healthy volunteers were recruited.Respiratory-triggered 3D true SSFP sequences on a 1.5T MRI system combined with T-SLIP placed on the spleen and mesenteric area were performed.The portographic images were generated from the subtraction between the pulse on and off images.According to the difference in inversion time(TI)of T-SLIP,four image groups group A(TI of 1300 ms),group B(TI of 1100 ms),group C(TI of 900 ms)and group D(TI of 700 ms),were assigned and compared to detect the optimal TI for portography.For quantitative analysis,the signal intensity(SI)of left and right liver lobe,the large vessels as main,right and left portal vein(MPV,RPV and LPV,respectively)and small vessels as branches of segments four(P4),six(P6)and eight(P8)were measured.The relative SI of MPV,RPV and LPV,as well as P4,P6 and P8 were also compared.For qualitative evaluation,the quality score of visualization was also evaluated using a 4-point scale.One-Way ANOVA and LSD test were used for comparison of quantitative data,and Friedman signed rank test was used for comparison of qualitative scores. RESULTS: In 52 sequences of 13 volunteers,the selective visualization of the portal vein was all successfully conducted.Quantitative evaluation showed significant increased SI at the left lobe between C and D groups and A and B groups(comparison of group C to group A and BP=0.004,0.011;comparison of group D to group A and BP=0.001,0.004),while relative SI of LPV of groups C and D were lower than groups A and B(comparison of group C to group A and BP=0.015,0.015;comparison of group D to group A and BP=0.000,0.000).The relative SI of MPV in group D were decreased than groups A(P=0.000),B(P=0.000),and C(P=0.019).There was no significant difference in relative SI of small vessels among four groups(P>0.05).The image score of portal vessels in four groups also showed no differences(P>0.05). CONCLUSIONS: 3D true SSFP scan with T-SLIP enabled selective non-CE visualization of the portal vein with digital subtraction method.A fixed TI of both 1300 and 1100 ms can be preferable.

Association of a rare haplotype in Kinesin light chain 1 gene with age-related cataract in a han chinese population.

PURPOSE: The causal genes for congenital cataract are good candidates for the genetic susceptibility for age-related cataract (ARC). The aim of this study was to investigate association between the polymorphisms in the causal genes for congenital cataract and ARC in a Chinese population. Meanwhile, we performed the replication study for previous identified risk genes for ARC. METHODS: We recruited 212 sporadic Han Chinese patients with age-related cataracts (ARC) and 172 normal controls in this study. We analyzed 31 SNPs from 13 genes which mostly possible contributes the progress of ARC in a Chinese population, comprising 212 cataract patients and 172 controls. Polymorphism-spanning fragments were amplified by using the multiplex polymerase chain reaction (PCR) and genotyped using primer extension method in MassARRAY platform. Allelic and haplotypic difference in the frequencies were estimated using the SHEsis software platform. P-value was adjusted by the Bonferroni correction. RESULTS: There was no difference in the frequencies of the genotype and allele of the all SNPs between the patients with ARC and the controls. In the haplotypic analysis, the haplotypes consisting of rs7154572, rs7150141 and rs12432994 in Kinesin Light Chain 1 Gene (KLC1) showed significant association with ARC (p = 0.000878). A rare haplotype CGT was more frequent in patients (p = 0.000106, and p = 0.00795 after corrected for 75 tests). CONCLUSIONS: Our study provides evidence that the combined effect of three variants within the KLC1 gene may predispose to ARC, but the precise mechanism needs further investigating.

No association between EGR gene family polymorphisms and schizophrenia in the Chinese population.

Early growth response (EGR) genes are thought to have a role in the pathogenesis of schizophrenia because of their conserved DNA binding domain and biologically activity in neuronal plasticity. This zinc-finger motif could influence gene post-translational modification and expression. The multigenetic association model, using markers in genes of similar or antagonistic biological effects within a signal pathway or gene family, might be more appropriate to this aspect of the schizophrenia hypothesis than the single gene strategy. In this study we investigated the role of EGR1, EGR2, EGR3 and EGR4 within the EGR family. Taqman technology was used to examine 12 single nucleotide polymorphisms (SNPs) covering these four genes in 2044 Chinese Han subjects. Case-control analyses were performed to detect association of these 4 genes with schizophrenia and multifactor dimensionality reduction (MDR) analysis was employed to examine their potential gene-gene interaction in schizophrenia. Neither allelic nor genotypic single-locus tests revealed any significant association between EGR1-4 and the risk of schizophrenia nor was any such association found with regard to interaction within EGR1-4 (p(min)=0.623, CV Consistency=10/10). We concluded that although multiple candidate genes are involved in schizophrenogenic development, the EGR family may not play a major role in schizophrenia susceptibility in the Chinese Han population.

Association between a polymorphism of the HTR3A gene and therapeutic response to risperidone treatment in drug-naive Chinese schizophrenia patients.

OBJECTIVES: Certain components of the serotonin system have been known for some time to be risk factors for schizophrenia. Few studies have, however, focused on the association between the therapeutic responses to atypical antipsychotics, such as risperidone, and polymorphisms of the 5-HT3 receptor, the only ionotropic ligand-gated serotonin receptor, even though there have been some genetic clues linking HTR3A and schizophrenia. We therefore postulated that such a polymorphism might be an explanatory factor in the diversity of response to risperidone treatment. METHODS: The study recruited 107 drug-naive Chinese schizophrenia patients who were given 8 weeks of risperidone monotherapy and it explored three of four single nucleotide polymorphisms spanning HTR3A for possible association with therapeutic improvement, using the Positive and Negative Symptom Scale. RESULTS: Significant correlation between the baseline score and therapeutic improvement was observed in each subscale (P<0.001). Statistical analysis revealed association between genotypes of g.14396A>G polymorphism (rs1176713) and score reductions of negative and general subscales after adjusting for the influence of the baseline scores of each subscale [P (F, d.f.)=0.026 (3.763, 2), 0.023 (3.937, 2) respectively]. One haplotype, C-A-G, contributed to an effective response in general symptoms (chi(2)=7.3, P=0.007, odds ratio=3.371). CONCLUSION: The results of this study are the first to suggest that the polymorphism of HTR3A may be a useful predictor of therapeutic response to risperidone treatment in Chinese schizophrenic patients, although these conclusions should be treated with caution because of the intricacy of the variety of the therapeutic effects to risperidone.

An association study between PPP1R1B gene and schizophrenia in the Chinese population.

Schizophrenia has been linked with dysfunctions of glutamatergic, dopaminergic, and serotonergic neurotransmission. Dopamine- and cAMP-regulated phosphoprotein of relative molecular mass 32 kDa (DARPP-32), encoded by PPP1R1B (protein phosphatase 1, regulatory/inhibitor subunit 1B) gene, is enriched in neostriatal medium spiny neurons. It plays a key regulator role in dopaminergic and glutamatergic signaling pathways. The combined evidence from reduced DARPP-32 expression in the dorsolateral prefrontal cortex (DLPFC) in schizophrenic patients and from abnormalities in mice with a genetic deletion of DARPP-32 or with point mutations in phosphorylation sites of DARPP-32 suggested that it would be worthwhile to investigate the association between DARPP-32 and schizophrenia. In the present study, we genotyped five single nucleotide polymorphisms (SNPs) in the PPP1R1B gene and conducted a case-control study involving 520 schizophrenic patients and 386 healthy subjects drawn from the Chinese population. No allelic, genotypic or haplotypic association was found. However, our results do not preclude the possibility that the PPP1R1B is a susceptibility gene for schizophrenia in the Chinese population, since, as a central molecular switch, PPP1R1B may contribute to schizophrenia by interacting with other genes. Further functional analysis and genetic association studies are needed to determine the potential roles of PPP1R1B and other related genes in the pathophysiology of schizophrenia.

Response of risperidone treatment may be associated with polymorphisms of HTT gene in Chinese schizophrenia patients.

Serotonin transporter (5-HTT) is a key component of the serotonergic neurotransmitter system. Few studies have focused on polymorphisms of the serotonin transporter and antipsychotic response and, in particular, there have so far been no published studies on the association between the serotonin transporter and response to risperidone. This study examined the relationship between two polymorphisms of the serotonin transporter and the efficacy of risperidone treatment in 129 patients with schizophrenia. Our results revealed that patients with l allele of HTTRLP showed a greater improvement than those without l allele on the overall brief psychiatric rating scale (BPRS) (P=0.025). But no such relationship was found for the HTTVNTR. In haplotype analysis, the frequency of L-12 haplotype showed a significant difference between the responder group and the non-responder group (P=0.005). Our study has, for the first time, produced evidence that the potential for therapy in patients with schizophrenia is related to the HTTRLP polymorphism in the HTT gene and haplotype L-12 may help to predict risperidone treatment efficiency.

Case-control study and transmission disequilibrium test provide consistent evidence for association between schizophrenia and genetic variation in the 22q11 gene ZDHHC8.

Genetic variants in the 22q11 gene ZDHHC8, which encodes a putative transmembrane palmitoyltransferase, has been associated to schizophrenia in family-based linkage disequilibrium (LD) studies. The single nucleotide polymorphism (SNP) rs175174 (A/G), which had the strongest association, has been shown recently to regulate the level of the fully functional transcript by modulating the retention of intron 4 of ZDHHC8. In this work, we genotyped three genetic variants within the ZDHHC8 locus and conducted association studies in both population- and family-based samples of the Han Chinese population. The three polymorphisms spanning approximately 5.5 Kb were detected to be in significant LD. Our results provided compelling supportive evidence for association of the variants within the ZDHHC8 locus with schizophrenia but revealed different risk allele at SNP rs175174. The G allele was significantly more common in cases than in controls (69.47 : 59.96%; P=0.000018) and excess transmission of the same allele was confirmed in the family-based transmission disequilibrium test (transmitted/non-transmitted=87 : 54; P=0.0055). Both sample sets even shared the same risk haplotype with similar frequency. Our current data presents consistent association results obtained from both case-control and family-based samples in a same laboratory under the same experimental condition. Despite the potential genetic heterogeneity, our independent findings further support that the 22q11 region is likely to harbor candidate schizophrenia susceptibility genes.

An association between polymorphisms of the interleukin-10 gene promoter and schizophrenia in the Chinese population.

Immunological abnormalities have been found to be associated with schizophrenia for decades. Cytokines are key proteins involved in the immune system activation. Interleukin-10 (IL-10), an important immunoregulatory cytokine, is located on chromosome 1q31-32, a region previously reported to be linked to schizophrenia in genetic studies. Thus, a study was carried out on the association between schizophrenia and three single nucleotide polymorphisms in the promoter region of IL-10 gene. Totally, 341 patients and 334 controls of Chinese descent were analyzed. Statistically significant differences were observed in both allelic and genotypic frequencies of the -592A/C polymorphism (Allele, chi(2)=4.43, df=1, P=0.032, odds ratio (OR)=1.26, 95% CI 1.02-1.56; Genotype, chi(2)=6.18, df=2, P=0.044) while the other two polymorphisms did not show such differences. The observed haplotype distributions revealed a significant association with schizophrenia (P=0.0008). These data suggest that the IL-10 gene may confer susceptibility to the development of schizophrenia in the Chinese population.

Family-based association study of synapsin II and schizophrenia.

Synapsin II has been proposed as a candidate gene for vulnerability to schizophrenia on the basis of its function and its location in a region of the genome implicated by linkage studies in families with schizophrenia. We recently reported positive association of synapsin II with schizophrenia in a case-control study (Chen et al. 2004). However, since case-control analyses can generate false-positive results in the presence of minor degrees of population stratification, we have performed a replication study in 366 additional Han Chinese probands and their parents by use of analyses of transmission/disequilibrium for three in/del markers and three single-nucleotide polymorphisms. Positive association was observed for rs2307981 (P =.02), rs2308169 (P =.005), rs308963 (P =.002), rs795009 (P =.02), and rs2307973 (P =.02). For transmission of six-marker haplotypes, the global P value was.0000016 (5 degrees of freedom), principally because of overtransmission of the most common haplotype, CAA/-/G/T/C/- (frequency 53.6%; chi (2) = 20.8; P =.0000051). This confirms our previous study and provides further support for the role of synapsin II variants in susceptibility to schizophrenia.