Siyue Li

Association Between Promoter Variants of Interleukin-18 and Schizophrenia in a Han Chinese Population

An increasing amount of evidence suggests that interleukin-18 (IL-18) plays a pivotal role in the pathophysiology of schizophrenia. However, association between single nucleotide polymorphism of IL-18 and the risk of schizophrenia has not been clarified. This study examined whether two promoter polymorphisms -137 G/C (rs187238) and -607 C/A (rs1946518) of IL-18 were associated with schizophrenia and six clinical symptoms (disorder of perception, thought disorder, disturbance of emotion, disorder of behavior and volition, suicide action, and aggressive action) to provide data for screening high-risk Han Chinese individuals. Three hundred seventy-two schizophrenic patients and 353 healthy controls from a Han Chinese population were examined to assess their genotype and allele frequencies of the two promoter polymorphisms of IL-18. The genotype distributions in both patients and controls were within Hardy-Weinberg equilibrium. No significant differences were observed in the genotype or the allele frequencies of the two single-nucleotide polymorphisms between patients and controls. However, genotype frequencies of -607 C/A showed significant differences between patients and controls in the appearance of perception disorder (χ2 = 6.153, p = 0.046). A significant difference was detected in -137 G/C between patients and controls in the appearance of aggressive action (χ2 = 3.909, p = 0.048). In conclusion, IL-18 gene promoter polymorphisms may not contribute to the susceptibility of schizophrenia in a Han Chinese population, but two single-nucleotide polymorphisms, -137 G/C and -607 C/A, may play a role in the development of perception disorder and aggressive action, respectively.

Donor or recipient TNF-A -308G/A polymorphism and acute rejection of renal allograft: A meta-analysis.

BACKGROUND Results from published studies on the association of donor or recipient TNF-A -308G/A polymorphism with acute rejection (AR) of renal allograft are inconsistent. We performed a meta-analysis to summarize the possible association. METHODS Studies were identified by searching PUBMED, EMBASE and Chinese National Knowledge Infrastructure (CNKI) databases until March 22, 2011. Meta-analysis was performed in a fixed/random-effect model using Revman 5.0.25 and STATA10.0. RESULTS Eight studies evaluating the association between donor TNF-A -308G/A polymorphism and acute rejection of renal allograft were identified. Pooled OR based on 460 cases (whose recipient developed AR) and 623 controls (whose recipient did not develop AR) was 1.44 (95% CI=1.05-1.99, p=0.03). No association was detected in the subgroup analysis based on ethnicity. 28 studies evaluating the association between recipient TNF-A -308G/A polymorphism and acute rejection were identified. Pooled OR based on 1411 cases (patients did not develop AR) and 2088 controls was 1.39 (95% CI=1.06-1.82, p=0.02). Two studies evaluating the association between recipient TNF-A -308G/A polymorphism and recurrent acute rejection were identified. Pooled OR based on 225 cases (patients with ≤1 AR) and 34 controls (patients with ≥2 AR) was 0.28 (95% CI=0.13-0.62, p=0.002). CONCLUSIONS Our meta-analysis provided evidence that TNF2 allele positive genotype of donor or recipient was associated with increased risk of incidence of acute rejection of renal allograft. Recipient TNF2 allele positive genotype is also associated with increased risk of recurrence of acute rejection of renal allograft. However, additional studies with large sample size and better study designs are warranted to verify our finding.

Association Analysis Between the rs11136000 Single Nucleotide Polymorphism in Clusterin Gene, rs3851179 Single Nucleotide Polymorphism in Clathrin Assembly Lymphoid Myeloid Protein Gene and the Patients with Schizophrenia in the Chinese Population

Clusterin (CLU) and clathrin assembly lymphoid myeloid (CALM) protein are implicated in the function of neuronal synapses. However, to our knowledge, whether they play roles in the maldevelopment of synaptic pathways in schizophrenia has not been studied. The purpose of this study was to examine whether single nucleotide polymorphisms rs11136000 within the CLU gene and rs3851179 within the CALM gene, were associated with schizophrenia. Polymorphisms rs11136000 and rs3851179 were analyzed among 184 Chinese patients with schizophrenia and 162 healthy controls. The high-resolution melting method was used to genotype the two loci. Patients with schizophrenia and with family history showed a significant increase of allele C frequency in rs11136000 in comparison to normal controls (p = 0.03). In addition, the C allele frequency was also higher in patients with negative symptoms (p = 0.04). In contrast, allele and genotype frequencies of rs3851179 did not show significant differences between patients and normal subjects or between patients with different symptoms. The results of this study show that polymorphism of the CLU gene may confer symptomatic specificity in schizophrenia, whereas polymorphism of the CALM gene does not affect susceptibility to schizophrenia.

IL-28B genetic variant is associated with the risk of schizophrenia in the Chinese Han population.

Schizophrenia is a severe psychiatric disorder. Although its exact cause is unknown, it is widely accepted that environmental factors and genes integrate in the pathogenesis of schizophrenia. 19q13, which contains IL-28B, is a newly identified potential susceptibility locus. IL-28B is a cytokine that functionally has anti-viral activity, but, structurally, is related to the interleukin-10 family. Both virus infection and cytokine changes have been documented in schizophrenia. We selected the single-nucleotide polymorphism rs8099917, which is associated with IL-28B gene expression, to study its relationship to the susceptibility to schizophrenia. A total of 256 Chinese patients with schizophrenia and 329 healthy controls were studied. Both genotype and allele frequencies showed significant differences between patients and normal subjects (p=0.03 and p=0.04, respectively). Our study suggested that the frequency of allele T was a risk factor for the susceptibility of schizophrenia (odds ratio [OR]=1.76, 95% confidence interval [CI]=1.03-3.03). When all subjects were grouped by symptoms, both the genotype and the allele frequency were associated with patients having disorganized speech (genotype: χ(2)=5.75, p=0.02; allele: χ(2)=5.41, p=0.02, OR=3.67, 95% CI=1.14-11.82) and negative symptoms (genotype: χ(2)=5.09, p=0.02; allele: χ(2)=4.80, p=0.03, OR=1.95, 95% CI=1.06-3.56) as well as cognitive symptoms (genotype: χ(2)=5.97, p=0.02; allele: χ(2)=5.53, p=0.02, OR=2.04, 95% CI=1.11-3.74). The results in this study may lead to a better understanding of the etiology of schizophrenia.

Molecular epidemical characteristics of Lamivudine resistance mutations of HBV in southern China.

Summary Background Lamivudine (LMV), as the preferred oral drug for use in treatment of HBV, always results in development of resistance mutations after long-term treatment. In this study we investigated chronic hepatitis B (CHB) patients in southern China to determine whether different HBV genotypes affect the incidence of LMV resistance mutations. Material/Methods The study recruited 185 CHB patients living in southern China. Enzyme-linked immunosorbent assay was used to test for HBV serological markers, and HBV DNA was quantified by real-time PCR. Sequencing was performed to detect HBV genotypes and mutations. Results There were 49.19% (91/185) CHB patients with HBV resistant to LMV. Only 2 genotypes were found: B and C; 62.16% (115/185) of patients were infected with genotype B HBV and 37.84% (70/185) of patients were infected with genotype C HBV. The incidence rate of LMV resistance was not significantly different between genotype B and C (49.57% vs. 48.57%, P>0.05). For the mean age and sex ratio, no significant difference was found. The pattern of rtM204I alone was predominantly observed (36.26%, 33/91), followed by rtM204V+rtL180M (23.08%, 21/91). The overall incidence rate of rtM204I mutation in genotype B (45.61%, 26/57) was more frequent than that in genotype C (20.59%, 7/34) (45.61% vs. 20.59%, P<0.05), but the incidence rate of other mutation patterns was not significantly different between genotypes B and C. Conclusions Our results emphasize that a LMV resistance test before treatment is of great importance in rational and optimal CHB therapy.