Association Analysis of Proteasome Subunits and Transporter Associated with Antigen Processing on Chinese Patients with Parkinson's Disease / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Proteasome subunits (PSMB) and transporter associated with antigen processing (TAP) loci are located in the human leukocyte antigen (HLA) Class II region play important roles in immune response and protein degradation in neurodegenerative diseases. This study aimed to explore the association between single nucleotide polymorphisms (SNPs) of PSMB and TAP and Parkinson's disease (PD).</p><p><b>METHODS</b>A case-control study was conducted by genotyping SNPs in PSMB8, PSMB9, TAP1, and TAP2 genes in the Chinese population. Subjects included 542 sporadic patients with PD and 674 healthy controls. Nine identified SNPs in PSMB8, PSMB9, TAP1, and TAP2 were genotyped through SNaPshot testing.</p><p><b>RESULTS</b>The stratified analysis of rs17587 was specially performed on gender. Data revealed that female patients carry a higher frequency of rs17587-G/G versus (A/A + G/A) compared with controls. But there was no significant difference with respect to the genotypic frequencies of the SNPs in PSMB8, TAP1, and TAP2 loci in PD patients.</p><p><b>CONCLUSION</b>Chinese females carrying the rs17587-G/G genotype in PSMB9 may increase a higher risk for PD, but no linkage was found between other SNPs in HLA Class II region and PD.</p>

Expression of PSF1 in colon cancer tissues and its effect on the proliferation of colon cancer cells / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To detect the expression of PSF1 (partner of Sld five 1) in colon cancer specimens, and to explore the effect of RNA interference targeting PSF1 on the proliferation of colon cancer cells and its mechanism.</p><p><b>METHODS</b>Expression level of PSF1 protein in colon cancer specimens was detected by Western blot in 40 patients with colon cancer from May 2004 to December 2006. The short hairpin RNA (shRNA) plasmid targeting PSF1 was transfected into LOVO, HT-29 and HCT116 cells with liposome, then the expression level of PSF1 protein was measured by Western blot, the effect of PSF1 shRNA plasmid transfection on cell proliferation by MTT assay, anchorage-independent growth by soft agar colomy-formation assay, and PSF2, PSF3 and SLD5 mRNA expression by quantitative reverse transcription polymerase chain reaction.</p><p><b>RESULTS</b>The relative expression level of PSF1 protein in colon cancer tissues was 0.485±0.113, which was significantly higher than that in adjacent normal mucosa tissues (0.056±0.014, P<0.01). Western blot showed that the expression level of PSF1 protein was significantly decreased in colon cancer cells transfected with PSF1 shRNA plasmid. After PSF1 shRNA plasmid transfection, cell proliferation was significantly suppressed, the soft agar colony-forming rates of LOVO, HT-29 and HCT116 cells were significantly lower than those in control groups (P<0.05), meanwhile the expression levels of PSF2, PSF3 and SLD5 mRNA were significantly decreased (P<0.05).</p><p><b>CONCLUSIONS</b>PSF1 is significantly up-regulated in colon cancer tissues compared with adjacent normal mucosa tissues. ShRNA plasmid targeting PSF1 can inhibit the expression of PSF1 gene, suppress the proliferation of colon cancer cells, suggesting that it may be a new therapeutic target for colon cancer.</p>

Relationship between rs1057141 and rs1135216 polymorphisms of TAP1 gene and allergic rhinitis in Xinjiang Han people / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To investigate the association between transporter associated with antigen processing 1 (TAP1) rs1057141 and rs1135216 gene polymorphisms and predisposition to allergic rhinitis (AR) in Xinjiang Han people.@*METHOD@#A case control study was conducted. The region of the TAP1 * rs1057141 and rs1135216 was studied in 150 Xinjiang Han people with allergic rhinitis and 150 normal controls by using SNaPshot system, and these data were compared with other ethics groups in the world according to the NCBI gene bank.@*RESULT@#The genotypes distribution of the group were in the Hardy-Weinberg equilibrium(P>0.05). The frequencies of three genotypes(G/G, G/A, A/A) of TAP1 * rs1057141 were 4.00%, 30.00%, 66.00% in controls and 2.70%, 33.30%, 64.00% in AR groups , which showed no difference (P>0.05). The frequencies of three genotypes (G/G,G/A,A/A) of TAP1 * rs1135216 were 2.0%, 28.7%, 69.3% in controls and 1.30%, 27.30%, 71.40% in AR groups, which showed no difference either (P>0.05). According to the NCBI database, there was difference between Xinjiang Han people and other ethnics in the world.@*CONCLUSION@#Lacking association was found between the mutation of TAP1 * rs1057141, rs1135216 gene G allele and allergic rhinitis in the Xinjiang Han people. Maybe TAP1 * rs1057141, rs1135216 were not susceptibility genes to AR. And apparent differences existed in TAP1 gene polymorphisms between Xinjiang Han people and other ethnic groups in the world.

Relationship between TAP gene promoter methylation and cervical lesions with HPV infection in Uyghur women / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the relationship between TAP (transporter associated with antigen processing) gene promoter regional methylation level and cervical lesions with HPV infection in Uyghur women.</p><p><b>METHODS</b>A specialized software was used to design specific primers of CpG island fragments of TAP1 and TAP2 gene promoter for PCR amplification, bisulfitemodified SiHa cancer cell DNA for PCR amplification, cloning and sequencing analysis to obtain the relevant information on the gene base sequence methylation of CpG sites. Seventy-eight fresh cervical tissue samples from Uyghur women with cervicitis (number = 15), cervical intraepithelial neoplasia (CIN, number = 30) and cervical squamous cell carcinoma (number = 33) were collected. The methylation level of TAP1 and TAP2 gene promoter regions was detected using MassArray DNA technology. HPV infection status was determined by HPV gene chips. The relationship between CpG-island methylation of gene promoter regions and HPV infection was then analyzed.</p><p><b>RESULTS</b>Each TAP1 and TAP2 gene corresponding target fragment contained 23 and 8 CpG sites. There were 5 and 8 CpG sites methylation occurred in SiHa cervical cancer cells genomic DNA respectively. The TAP1 methylation level increased steadily with the severity of cervical lesions. The methylation levels in cervical squamous cell carcinoma and CIN (0.048 ± 0.039 and 0.037 ± 0.026, respectively) were higher than that of normal cervical tissue (0.035 ± 0.029, P < 0.05). Although TAP2 gene methylation level also demonstrated similar changes, the difference however was not statistically significant (P > 0.05). HPV gene chip detected 13 HPV genotypes, with HPV16 infection rate being 66.7% (52/78). The methylated proportion of TAP1 positively correlated with HPV16 infection (χ(2) = 6.08, P = 0.039).</p><p><b>CONCLUSION</b>TAP1 methylation is a remarkable phenomenon occurring in a range of cervical lesions and significantly associated with cervical HPV infection.</p>

Role of ABCB1 and ABCG2 in the multidrug resistance of hypopharyngeal carcinoma FaDu cell line / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To investigate the expression of multidrug resistance gene ABCB1 and ABCG2 in FaDu cells (human hypopharyngeal carcinoma cell line) and the multidrug resistance (MDR) cell lines FaDu/T transformed from FaDu cells by taxol and underlying mechanisms of MDR.</p><p><b>METHODS</b>The multidrug resistance sensitivities of FaDu and FaDu/T to cisplatin (DDP), 5-fluorouracil (5-FU), doxorubicin (Dox), and vincristine (VCR) were examined by methyl-thiazolyl-tetrazolium (MTT) assay. The mRNA and protein expressions of multidrug resistance genes ABCB1 and ABCG2 were analysed with RT-PCR, Western blot and laser confocal microscopy. JNK signal proteins were detected through Western blot.</p><p><b>RESULTS</b>The multidrug resistance of FaDu/T cells to Taxol, DDP, 5-FU, ADM and VCR was more than that of FaDu cells. The expression of ABCB1 in FaDu/T cells was significantly higher than that in FaDu cells (t = 22.42, P < 0.05), but the expression of ABCG2 in FaDu/T cells was significantly lower than that in FaDu cells (t = 10.06, P < 0.05). JNK signal was inhibited in FaDu or FaDu/T cells and the inhibited JNK was reactivated by taxol or anisomycin (an activator for MAPK signal transduction pathways). Anisomycin down-regulated the expression of ABCB1 (F = 33.72, P < 0.05) and up-regulated the expression of ABCG2 (F = 220.16, P < 0.05) in FaDu/T cells, but not in FaDu/T cells pretreated by JNK inhibitor SP600125 (P > 0.05).</p><p><b>CONCLUSION</b>The overexpression of ABCB1 and the down-regulation of ABCG2 in FaDu/T cells were the main features of MDR in hypopharyngeal carcinomas, in which JNK signal transduction pathways could play an important role.</p>

Association of antigen processing machinery and HLA class I defects with clinicopathological outcome in laryngeal squamous cell carcinoma / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To investigate the role of antigen-processing machinery (APM) component defects in HLA class I antigen down-regulation in laryngeal squamous cell carcinoma (SCC) and to assess the clinical significance of these defects.</p><p><b>METHODS</b>Fifty-one formalin-fixed, paraffin-embedded SCC specimens were examined for the expressions of APM component transporter associated with antigen processing (TAP1) and low molecular weight polypeptide (LMP-7) and HLA class I antigen by immunohistochemistry.</p><p><b>RESULTS</b>HLA class I antigens, TAP-1 and LMP-7 expressions were down-regulated in 56.9% (29/51), 39.2% (20/51) and 45.1% (23/51) of the tested specimens respectively, whereas HLA class I antigens, TAP-1 and LMP-7 expressions lost in 21.6% (11/51), 33.3% (17/51) and 27.5% (14/51) of the tested specimens respectively. TAP-1 and LMP-7 expressions were significantly correlated with HLA class I antigen expression (r=0.460, P<0.05 and r=0.685, P<0.05, respectively). HLA class I antigens down-regulation was significantly correlated with T stage (χ2=8.61, P<0.05). Both TAP-1 and LMP-7 down-regulations were significantly correlated with T stage (χ2 values were 9.72 and 8.97 respectively, P<0.05) and TNM stage (χ2 values were 9.18 and 7.70 respectively, P<0.05). TAP-1, LMP-7 and HLA class I antigen down-regulations were significantly associated with reduced patients' overall survival (P<0.05) and disease-free survival (P<0.05). Multivariate analysis showed lymph node metastasis, recurrence and HLA class I antigen down-regulation were unfavorable prognostic factors (P<0.05).</p><p><b>CONCLUSIONS</b>Down-regulated expressions of HLA class I antigen and APM component TAP-1 and LMP-7 occur frequently in laryngeal squamous cell carcinoma, by which cancer cells could avoid immune surveillance, while HLA class I antigen down-regulation is a major contributing factor to tumour progression and mortality.</p>

Association of defective HLA-I expression with antigen processing machinery and their association with clinicopathological characteristics in Kazak patients with esophageal cancer / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>It has been confirmed that defective expression of human leukocyte antigen class I (HLA-I) molecules can contribute to the immune evasion of cancer cells in some types of cancer. The aim of this study was to examine the expression of HLA class I antigen and the antigen-processing machinery (APM) components in esophageal squamous cell carcinoma (ESCC) and their role in high risk human papillomavirus (HPV) infection, and to analyze their association with histopathological characteristics in the Kazak ethnic group.</p><p><b>METHODS</b>A total of 50 formalin-fixed, paraffin-embedded ESCC lesions were collected from the First Affiliated Hospital of Xinjiang Medical University, China. The expression levels of HLA-I antigen and APM components were determined by immunohistochemistry; the HPV DNA were detected using polymerase chain reaction (PCR).</p><p><b>RESULTS</b>A high frequency of down-regulation or loss of expression of HLA and APM components were found in esophageal cancer in Kazak people. HLA-I, TAP1, CNX, LMP7, Erp57, Tapasin and ERAP1 were down-regulated in 68%, 44%, 48%, 40%, 52%, 32% and 20% of ESCC lesions then, respectively. The loss of expression of HLA-I antigen was significantly correlated with part of the APM components and positively correlated with high risk HPV16 infection. TAP1, CNX, LMP7, Erp57 and Tapasin loss were significantly associated with tumor grading, lymph node metastasis and depth of invasion (P < 0.05).</p><p><b>CONCLUSION</b>Our results suggest that APM component defects are a mechanism underlying HLA-I antigen down-regulation in ESCC lesions, and indicate that the loss expression of HLA-I and APM components will become an important marker of ESCC and analysis of HLA-I and APM component expression can provide useful prognostic information for patients with ESCC from the Kazak ethnic group.</p>

Transporter associated with antigen processing 1 637A/G gene polymorphisms and susceptibility to nasopharyngeal carcinoma in Han population in Yunnan Province, China / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To study the relationship between 637A/G gene polymorphisms of the transporter associated with antigen processing 1 gene and nasopharyngeal carcinomas (NPC) and to find out the susceptible genes of NPC in Han population in Yunnan Province, China.</p><p><b>METHODS</b>Two hundred and thirty-three cases with NPC and 296 cases matched cancer-free controls were genotyped for the TAP1 637A/G polymorphism by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Epstein-Barr virus infection was detected by PCR. The adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated by using unconditional logistic regression model.</p><p><b>RESULTS</b>Contrast with homozygous TAP1 637 AA, G allele significantly increasing risk of NPC was associated with homozygous 637 GG OR = 4.26 (95%CI were 2.08 - 8.66, P < 0.001) and heterozygous 637 AG OR = 1.56 (95%CI were 1.12 - 2.33, P < 0.05). The subjects at least having one TAP1 637 G allele had OR of 1.88 (95%CI were 1.35 - 2.82, P < 0.001). Furthermore, EBV infection may increase the risk of developing NPC interacting with TAP1 637 A/G polymorphism OR = 2.76(95% CI were 1.69 - 4.63, P < 0.001).</p><p><b>CONCLUSIONS</b>The TAP1 637G allele is associated with the NPC in Han population in Yunnan China, EBV pathogenesis in NPC might be facilitated by polymorphisms in the TAP1 proteins.</p>

Distribution of tap1 and tap2 loci allelic and genotypic frequencies in Chinese Hans / 中国实验血液学杂志

This study was aimed to investigate the distribution and implication of tap1 (transporter associated with antigen processing) and tap2 loci allelic and genotypic frequencies. The distribution of tap1 and tap2 loci allelic and genotypic frequencies in 339 random samples of healthy Chinese Hans was analyzed by TaqMan PCR. Several genetic information about power of discrimination, cumulative DP, polymorphism information content, expected heterozygosity and observed heterozygosity were calculated. The results indicated that 5 tap1 alleles (tap1*0101, 020101, 020102, 0301 and 0401) and 4 tap2 alleles (tap2*0101, 0102, 0103 and 0201) were detected in all samples. 8 tap1 genotypes were found which account for 53.3% of the theoretic genotype and 6 tap2 genotypes were found which account for 60% of the theoretic genotype. The genotyping results of tap1 and tap2 both conform to the Hardy-Weinberg expectations (p > 0.05). Tap1*0101 (79.79%) and tap2*0101 (82.74%) are the most common alleles in Chinese Hans. It is concluded that tap1*0101 and tap2*0101 are most common alleles in Chinese Hans, tap1 and tap2 loci carry some power of individual discrimination and polymorphism information content. These two locl can be used for the research in the fields of human genetics, linkage analysis of genetic disease genes, paternity test and individual identification and so on.

Study on the association between polymorphism of TAP1 637 A/G alleles polymorphism and metabolic syndrome / 中华流行病学杂志

<p><b>OBJECTIVE</b>To explore the effect of the transporter 1 associated with antigen processing (TAP1) gene 637 A/G polymorphism on the risk of metabolic syndrome(MS).</p><p><b>METHODS</b>A case-control study was conducted on 138 based-community patients (68 males and 70 females, 61.31 +/- 11.00 years old) diagnosed as MS with 162 healthy subjects (74 males and 88 females, 48.73 +/- 11.66 years old) came from the same origin as cases. The allele polymorphisms TAP1 637 A/G was examined by the specificity restriction fragment length polymorphism-polymerase chain reaction(RFLP-PCR) method with genomic DNA. The effect of TAP1 637 A/G polymorphisms on MS were analyzed by multivariable unconditional logistic regression models.</p><p><b>RESULTS</b>The TAPI 637 A/G allele genotypes frequencies (83.3%, 16.7%) contribution in control group were consistent with the distribution predicted by Hardy-Weinberg equilibrium (chi2 = 1.46, P > 0.05). TAP1 637 G allele genotypes frequencies (26.1%) of cases were significantly higher than controls (16.7%) with P = 0.005. There were significant differences of AA (58.0%), AG (31.9%) and GG (10.1%) genotypes in cases than controls, AA (68.5%). AG (29.6%) and GG (1.9%) for recessive model and addictive model after age was adjusted with P value as 0.006 and 0.044, but no significant differences for dominant model (P = 0. 298). Results from recessive model with OR = 6.62, 95% CI :1.73-25.31, Addictive model with OR = 1.56, 95% CI:1.01-2.41 and one-way ANOVA analysis showed that systolic blood pressure(SBP) and diastolic blood pressure (DBP) levels of GG genotype were significantly higher than AA or AG genotype (P < 0.05) whereas no significantly statistical differences for other clinical characteristics.</p><p><b>CONCLUSION</b>The TAP1 637 allele A to G alteration or genotype AA to GG and AG to GG alterations could increase the risk of MS significantly, especially for SBP and DBP levels, and this positive association results might be helpful to support the biological role of TAP1 in MS but in need of larger sample size to provide more powerful evidences.</p>

Study on the mechanism of HLA-I-expressing regulation caused by the core region mutation of HBV adr subtype / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To study the influence and mechanism of HBV core region mutation on HLA-I expression.</p><p><b>METHODS</b>Eukaryotic expression vectors of HBV core region mutations L97, G87 and V60 were constructed and transfected into HepG2 cells. Then the expressions of HLA-I were detected by RT-PCR and Western blot. The mRNA of antigen-presentation-associated genes, including LMP2, TAP1 and tapasin, were measured using RT-PCR.</p><p><b>RESULTS</b>Different levels of HBsAg in the supernatants of transfected cells were detected by ELISA. The HBsAg of the mutated groups was markedly higher than that of the wild ones. All the transfected cells expressed HLA-I molecules, especially the L97 group. It was also found that the mRNA of TAP1 gene was up-regulated, while the mRNA of LMP and tapasin genes had no changes.</p><p><b>CONCLUSION</b>The core region mutation of HBV can lower the expression of HBsAg; mutated groups and wild ones both can increase the expression of HLA-I molecules. The up-regulation of TAP1 gene expression might be the cause of these changes.</p>