Interleukin-6 promotor gene polymorphisms and susceptibility to chronic hepatitis B virus in Egyptians

AimTo investigate the association between IL-6 polymorphisms (?174G/C, ?572G/C and ?597G/A) and susceptibility to chronic hepatitis B virus (CHB) infection.MethodTotal 108 subjects with CHB infection and 102 healthy controls were enrolled in this study. IL-6 (?174G/C) was genotyped using Mutagenically separated Polymerase Chain Reaction (MS-PCR) while sequence specific primers-PCR (SSP-PCR) was used for studying ?572G/C and ?597G/A. IL-6 plasma level was measured using Enzyme-linked immunosorbent assay (ELISA).ResultsA significant increase (P < 0.01, P < 0.01, P < 0.001) in ?174GG, ?572GC and ?597GA; respectively in the CHB group compared to control group, while ?572GG genotype was significantly decreased (P < 0.01) in CHB patients. A significant increase (p < 0.01, p < 0.01) in ?174 G and ?597A alleles was observed in the CHB patient group; respectively. GGA haplotype is significantly increased (P < 0.05) while GCA haplotype is significantly decreased (P < 0.001) in the patient group. A moderate linkage disequilibrium (LD) (D′ = 0.719, r² = 0.474; P < 0.001) between IL-6 (?572G/C and ?597G/A) was observed. A significant reduction (P < 0.01) in IL-6 plasma level in CHB patients compared to healthy controls (22.28 ± 1.93 versus 32.08 ± 2.41), which was negatively correlated (r = ?0.216; P < 0.01) with HBV infection.ConclusionsThis study pointed to the potential role of IL-6 (?174G/C, ?572 G/C and ?597G/A) gene polymorphisms in the susceptibility to HBV infection. Our results allow for only preliminary conclusions due to relatively small sample size. There is a need for further larger scale studies to fully examine the possible relationship between these cytokine gene polymorphisms and the development of CHB.     

Association of PTPN22 gene polymorphisms with chronic hepatitis B virus infection in Chinese Han population

Lymphoid protein tyrosine phosphatase encoded by protein tyrosine phosphatase non-receptor 22 (PTPN22) gene plays an important regulatory role in T- and B-cell activation. This study investigated PTPN22 −1123G/C and intron 16 T/C polymorphisms in 372 patients with chronic hepatitis B virus (HBV) infection, 72 HBV infection resolvers and 273 healthy controls. Genotypic association tests between groups assuming codominant, dominant or log-additive genetic models were performed. In recessive model, PTPN22 −1123G/C genotype GG in healthy controls was more frequent than infection resolvers (P = 0.037, OR = 3.606, 95%CI = 1.079–12.053) and this genotype in HBV patients was more frequent than resolvers although the difference was not significant (P = 0.059). The PTPN22 intron 16 T/C genotype TC in cirrhosis patients was significantly higher than asymptomatic carriers (ASC) in codominant (P = 0.028, OR = 9.792, 95%CI = 1.281–74.832) and overdominant (P = 0.025, OR = 10.142, 95%CI = 1.332–77.214) models. This genotype in hepatocellular carcinoma (HCC) patients was significantly higher than ASC in codominant (P = 0.034, OR = 9.200, 95%CI = 1.176–71.990) and overdominant (P = 0.030, OR = 9.677, 95%CI = 1.241–75.442) models. These findings suggest that PTPN22 polymorphisms may predispose the chronicity or the development of cirrhosis and HCC in HBV infection.     

Mannose-binding lectin gene polymorphisms are not associated with susceptibility to hepatitis C virus infection in the Brazilian Amazon region

The present study compares the genotype frequencies between two population groups composed by 73 hepatitis C virus (HCV)-infected patients and 92 seronegative controls and investigates the role of allele variants as a possible factor in the susceptibility to HCV infection and the influence on disease progression. The identification of MBL*B and MBL*C alleles was performed by restriction fragment length polymorphism analysis of the 349-bp product using BanI and MboII restriction enzymes, respectively, and a polymerase chain reaction–sequence-specific polymorphism for discrimination of MBL*D. The analysis of allele and genotype frequencies between an HCV-infected group and seronegative controls did not indicate significant differences. The comparison of chronically infected subjects with and without liver cirrhosis was also not statistically significant. The odds ratio estimations were not significant, and the values obtained cannot suggest that the presence of allele variant MBL*B could have some influence in the risk of HCV infection progression to liver cirrhosis and that the presence of allele MBL*D could confer some protection against disease progression, but a larger sample size is necessary to confirm the present results.     

HLA-DQA1基因多态性和HBV感染结局的关联

目的 探讨人类白细胞抗原(HLA)DQA1基因多态性与乙型肝炎病毒(HBV)感染临床结局的关联.方法 临床收集慢性乙型肝炎(120例)、慢性HBV携带者(60例)、自限性HBV感染者(60例)三组病例,前两组诊断均经肝活检证实.聚合酶链反应序列特异性引物(PCR-SSP)法检测HLA-DQA1基因型,比较组间基因频率的差异.结果 (1)HLA-DQA1*0201在慢性乙型肝炎组的分布频率显著高于自限性HBV感染组(38.3% vs 5.8%,P<0.001,A=10.04,95% CI:4.48～22.48);HLA-DQA1*0102的分布频率显著低于自限性HBV感染组(9.6% vs 36.7%,P<0.001,A=0.183,95%CI:0.10～0.32).(2)HLA-DQA1*0201在慢性乙型肝炎组的分布频率显著高于慢性HBV携带者组(38.3% vs 7.5%,P<0.01,A=7.667,95% CI:3.7～15.87);HLA-DQA1*0102的分布频率显著低于慢性HBV携带者(20% vs 9.6%.P<0.01,A=0.424,95% CI:0.23～0.79).结论 HLA-DQAI基因多态性影响HBV感染临床结局,其中DQA1*0102呈保护作用,DQA1*0201可能促进HBV感染的慢性化和肝炎的发生.     

HLA-DQ遗传多态性与乙肝病毒感染结局相关

目的 探讨中国汉族人群人类白细胞抗原(HLA)-DQ基因单核苷酸多态性(rs9275572和rs9275319)与乙肝病毒感染结局的关系.方法 用TaqMan探针对纳入的921例样本进行HLA-DQrs9275572和rs9275319位点多态性的检测,921例血样本包括310例HBV相关慢性肝病者(CLD)、295例乙肝感染后自发清除者(SC)和316例健康对照者(HC).结果 1)Rs9275572 AG基因型有利于乙肝感染后病毒自发清除(OR 1.82,95％ CI 1.26～2.62;显性基因模型:OR 1.84,95％ CI 1.30～2.61).2)SNPrs9275319位点与乙肝易感性及感染后病毒的自发清除关系密切,携带rs9275319 C等位基因是一个保护因素(CLD vs HC:等位基因模型OR 0.49,95％ CI0.33 ～0.73,显性模型OR0.47,95％ CI0.31～0.72;CLD vs SC:等位基因模型OR 1.61,95％ CI 1.06～2.43,显性模型OR 1.57,95％口1.01 ～2.48).3)单体型T-G/T-A与乙肝易感性及感染后病毒自发清除相关.结论 HLA-DQ基因多态性与乙肝易感性及感染后病毒的自发清除密切相关.     

Association between Interleukin-27 gene polymorphisms and susceptibility to allergic rhinitis

Objectives

Allergic rhinitis (AR) is an inflammatory disorder of the upper airway. Interleukin-27 (IL-27), a novel IL-12 family member, has recently been reported to play a role in some immune-related disorders. This study was performed to evaluate the potential association of IL-27 polymorphisms with AR in a Chinese Han population.

Design and Methods

A case-control study was performed in 445 Chinese AR patients and 691 healthy controls. Three SNPs in the IL-27p28 gene, including rs153109, rs17855750 and rs181206, were detected using a polymerase chain reaction–restriction fragment length polymorphism assay (PCR–RFLP).

Results

A significantly increased prevalence of the rs153109 TT genotype and the T allele was found in AR patients, while a decreased prevalence of the CT and CC genotypes and the C allele was found. For rs153109, the TT genotype and the T allele were significantly associated with the risk of AR, but the CT and CC genotypes and the C allele decreased the risk of AR; for rs17855750, the TT genotype and T allele were risk factors for AR, and the GT genotype and G allele provided protection. TTT and TTC haplotypes in the IL-27p28 gene were positively correlated with AR, while CGT, CTC and CTT haplotypes were associated with a significantly decreased risk of AR.

Conclusion

This study indicates that IL-27p28 polymorphisms rs153109 and rs17855750 are likely involved in AR susceptibility, making them potentially useful genetic biomarkers for AR susceptibility in the Chinese Han population.     

Effects of human TRIM5alpha polymorphisms on antiretroviral function and susceptibility to human immunodeficiency virus infection

TRIM5α acts on several retroviruses, including human immunodeficiency virus (HIV-1), to restrict cross-species transmission. Using natural history cohorts and tissue culture systems, we examined the effect of polymorphism in human TRIM5α on HIV-1 infection. In African Americans, the frequencies of two non-coding SNP variant alleles in exon 1 and intron 1 of TRIM5 were elevated in HIV-1-infected persons compared with uninfected subjects. By contrast, the frequency of the variant allele encoding TRIM5α 136Q was relatively elevated in uninfected individuals, suggesting a possible protective effect. TRIM5α 136Q protein exhibited slightly better anti-HIV-1 activity in tissue culture than the TRIM5α R136 protein. The 43Y variant of TRIM5α was less efficient than the H43 variant at restricting HIV-1 and murine leukemia virus infections in cultured cells. The ancestral TRIM5 haplotype specifying no observed variant alleles appeared to be protective against infection, and the corresponding wild-type protein partially restricted HIV-1 replication in vitro. A single logistic regression model with a permutation test indicated the global corrected P value of < 0.05 for both SNPs and haplotypes. Thus, polymorphism in human TRIM5 may influence susceptibility to HIV-1 infection, a possibility that merits additional evaluation in independent cohorts.     

Association of interferon‐alpha gene polymorphisms with chronic hepatitis B virus infection

In this study, the association between the risk of chronic hepatitis B virus infection and the polymorphisms within promoter regions of IFN‐α1 and five genes was explored. This association study was performed on 180 Thai patients with chronic HBV infection [hepatocellular carcinoma (HCC) = 65 and non‐HCC = 115], 173 individuals with self‐limited HBV infection and 140 healthy controls. Our results showed that the A allele of ‐1823G/A SNP within IFNA1 gene was significantly associated with an increased risk of chronic HBV infection as compared to healthy individuals and self‐limited HBV group [OR (95% CI) = 2.20 (1.51–3.19), P = 0.000014 and OR (95% CI) = 1.61 (1.12–2.33), P = 0.0073, respectively]. The effect of A allele was similar to autosomal recessive in which the presence of AA genotype when compared to GG and GA conferred the OR of 2.79 (95% CI = 1.72–4.52, P = 0.0000085). By multifactor dimensionality reduction analysis, we found the interaction between IFNA5 (‐2529) and IFNA1 (‐1823) genes that gave the risk to chronic HBV infection, with the OR (95% CI) of the high‐risk to low‐risk group was 2.79 (1.77–4.40), P < 0.0001. However, further study in functional significance is required.     

Association of human platelet antigens polymorphisms with susceptibility to hepatitis C virus infection in Chinese population

Hepatitis C virus (HCV) is a major cause of chronic hepatitis. Previous studies have identified a number of single nucleotide polymorphisms that are associated with HCV infection. Human platelet antigens (HPAs) polymorphisms play an important role in several diseases. Here, we demonstrated the association of the HPA‐2, HPA‐3, HPA‐5 and HPA‐15 polymorphisms with susceptibility to HCV infection in Chinese population. Overall, 118 patients with HCV and 167 controls were genotyped for HPAs. There were no significant differences in the allele and genotype frequency distribution for the HPA‐3, HPA‐5 and HPA‐15 systems between the patients with chronic HCV infection and the healthy controls (p > .05). However, the genotype frequency of HPA‐2aa was significantly lower, while HPA‐2ab/bb was significantly higher in patients than that in the controls (p = .006). The allele frequency of HPA‐2a in patients was significantly lower than that in the control group (p = .005). In contrast, HPA‐2b in patients was significantly higher than that in the control group (p = .005). We conclude that HPA‐2 polymorphism is associated with susceptibility to HCV infection, and individuals carrying the HPA‐2b allele may have a higher risk of HCV infection compared with individuals carrying HPA‐2a.     

The roles of HLA-DQB1 gene polymorphisms in hepatitis B virus infection

Background

Infection with the hepatitis B virus (HBV) is an independent risk factor for liver cirrhosis and hepatocellular carcinoma, polymorphisms in HLA-DQB1 play an important role in HBV infections.

Methods

This study examined the relationships between HLA-DQB1 alleles and HBV infection susceptibility among 256 HBV carriers and 433 healthy controls. Venous blood samples were subjected to DQB1 high-resolution typing and testing for interferon-gamma, interleukin-4 (IL-4), interleukin-10, and DQB1 mRNA expression. A meta-analysis was also performed using relevant case–control studies that evaluated the associations of HLA-DQB1 alleles with HBV infection and clearance.

Results

We found that HLA-DQB1*06:03 protected against HBV infection. Levels of IFN-γ and IL-4 were significantly elevated in HBV cases with HLA-DQB1*06:05 (vs. HLA-DQB1*05:03), and the HBV group had higher DQB1 mRNA expression than the healthy control group with HLA-DQB1*05:03 and HLA-DQB1*06:02. The meta-analysis revealed that HLA-DQB1*04:01, HLA-DQB1*05:02, HLA-DQB1*05:03, and HLA-DQB1*06:01 were risk factors for HBV infection susceptibility, while HLA-DQB1*05:01, HLA-DQB1*06:03, and HLA-DQB1*06:04 protected against HBV infection. Spontaneous HBV clearance was associated withHLA-DQB1*06:04, while chronic HBV infection was associated with HLA-DQB1*02:01 and HLA-DQB1*05:02.

Conclusion

DBQ1 typing can be used to identify patients who have elevated risks of HBV infection (i.e., patients with HLA-DQB1*04:01, HLA-DQB1*05:02, HLA-DQB1*05:03, and HLA-DQB1*06:01) or elevated risks of chronic HBV infection (i.e., patients with HLA-DQB1*02:01 and HLA-DQB1*05:02).

     

Association of VEGF-A and KDR polymorphisms with the development of schizophrenia

AimSeveral approaches indicate different blood flow disturbances in schizophrenia. VEGF-A is widely recognized as one of the key molecules involved in the angiogenesis process through mainly its receptor KDR. The current work was designed to investigate the potential association between three polymorphisms (rs699947; rs833061 and rs3025039) in VEGF-A gene and two SNPs (rs2305948 and rs1870377) within KDR gene and predisposition to schizophrenia among the Tunisian cohort.MethodsWe carried-out a case-control study composed of 200 patients with schizophrenia and 200 healthy subjects using PCR-RFLP.ResultsOf all analyzed polymorphisms, only rs833061, rs3025039 and rs1870377) showed a significant risk for schizophrenia (P_Adjusted = 0.04, P_Adjusted=<0.001, P_Adjusted = 0.005 respectively). Following the stratified analysis, rs3025039 was more prevalent among undifferentiated form (P_Adjusted=<0.001) and more specifically with male sex (P_Adjusted=<0.001). Yet, rs1870377 was correlated with paranoid subtype (P_Adjusted = 0.002) and particularly with male sex (P_Adjusted = 0.005). We found also that rs699947 is associated to negative symptoms before and after treatment (P = 0.004; P = 0.001 respectively) and rs3025039 had an impact on positive and negative symptoms only after treatment (P = 0.03; P = 0.008 respectively). Haplotype analysis revealed a strong LD between rs833061 and rs3025039 only for controls and undifferentiated patients (P = 0.005). Moreover, the rs699947*C ～ rs833061*T ～ rs3025039*T haplotype, with only one mutated allele rs3025039*T, conferred a high risk to schizophrenia (P = 0.016) and, in particular, to undifferentiated and paranoid forms (P = 0.03; P = 0.02 respectively). Among the last-mentioned subgroup, we noticed another overrepresented haplotype (rs699947*A ～ rs833061*T ～ rs3025039*T; P = 0.01). Furthermore, the rs2305948*G ～ rs1870377*T haplotype carrying the minor allele rs1870377*T displayed increased frequencies in the whole group of patients and particularly among paranoid subtype (P = 0.013; P=<0.001 respectively).ConclusionOur results show that all SNPs associated with the development or the severity of schizophrenia, were subsequently correlated with a decrease in the VEGF-A levels or influence KDR binding affinity. These data need to be strengthened by further independent analyses.     

Association analysis of nine missense polymorphisms in the coagulation factor V gene with severe preeclampsia in pregnant Japanese women

The Leiden mutation in the coagulation factor V (F5) gene associated with preeclampsia in Caucasians has not been found in Japanese populations. We examined the association of 20 missense polymorphisms in the F5 gene in 133 pregnant Japanese women with preeclampsia and in 224 unrelated, healthy, pregnant Japanese women. Among nine polymorphisms identified in the subjects, the M385T and R485K polymorphisms were associated with preeclampsia (P = 0.05 and P = 0.02, respectively). Haplotype analysis indicated that the R485K polymorphism is truly associated with preeclampsia, whereas the association of the M385T polymorphism is due to linkage disequilibrium. Taken together with reports that the R485 allele yields poor factor V function in comparison with that of the K485 allele and that the F5 Leiden mutation is associated with preeclampsia in Caucasian populations, the findings of the present study suggest that the F5 gene is associated with preeclampsia in pregnant Japanese women. Received: October 18, 2001 / Accepted: December 17, 2001     

乙型肝炎与载脂蛋白基因多态性相关性研究

目的 探讨ApoAⅠ-75 Msp1、ApoB-Msp1、ApoCⅢ-Sst1、LRP5、ApoE基因多态性与乙型肝炎血清标志物不同模式之间的内在相关性.方法 将乙型肝炎血清标志物不同模式分为9组,每组80人,共720人份,采用SnaPshot法检测上述基因的多态性,最后用测序法佐证检测结果的准确性.结果 ApoAⅠ-75 Msp1、ApoE基因在乙型肝炎血清标志物不同模式之间差异有统计学意义(P＜0.05),ApoCⅢ-Sst1、ApoB-Msp1、LRP5基因则差异无统计学意义(P＞0.05).结论 ApoAⅠ-75Msp1、ApoE基因多态性与乙型肝炎血清标志物不同模式有相关性,ApoCⅢ-Sst1、ApoB-Msp1、LRP5与乙型肝炎血清标志物不同模式无相关性.     

Association of TNF-alpha promoter polymorphisms with the clearance of hepatitis B virus infection

The mechanisms underlying the resolution of hepatitis B virus (HBV) infection remain undetermined. Tumor necrosis factor-alpha (TNF-alpha) plays a pivotal role in host immune response to HBV, and the capacity for cytokine production in individuals has a major genetic component. The aim of this study was to examine whether TNF-alpha promotor polymorphisms are associated with the clearance of HBV infection. A total of 1400 Korean subjects were enrolled in two different groups: 'chronic carrier group' (CC; n=1109), who were repeatedly hepatitis B surface antigen (HBsAg)-positive, and 'subjects who spontaneously recovered' (SR; n=291), who were HBsAg-negative with antibodies to HBsAg and hepatitis B core antigen. TNF-alpha promoter polymorphisms at positions -1031T>C, -863C>A, -857C>T, -376G>A, -308G>A, -238G>A and -163G>A were determined and the genotype distributions of the CC and SR groups were compared. The TNF-alpha promoter alleles that were previously reported to be associated with higher plasma levels, i.e. the presence of the -308A allele (TNF-alpha-308A/G or A/A) or the absence of the -863A (TNF-alpha-863C/C) variant, were strongly associated with the resolution of HBV infection in three alternative analyzing models, i.e. TNF-alpha-308G>A (P=0.01) and TNF-alpha-863C>A (P=0.003-0.14), respectively. Haplotype analysis also revealed that TNF-alpha haplotype 1 [-1031T; -863C; -857C; -308G; -238G; -163G] and haplotype 2 [-1031C; -863A; -857C; -308G; -238G; -163G] were significantly associated with HBV clearance, showing protective antibody production and persistent HBV infection, respectively (P=0.003-0.02). Our findings imply that variations in the genes governing the levels of constitutive and inducible TNF-alpha might be an important factor, which might explain the variable outcome of HBV infection.     

乙型肝炎与载脂蛋白基因多态性相关性研究

目的探讨ApoAI-75Mspl、ApoB—Msp1、ApoCllI—Sst1、LRP5、ApoE基因多态性与乙型肝炎血清标志物不同模式之间的内在相关性。方法将乙型肝炎血清标志物不同模式分为9组,每组80人,共720人份,采用SnaPshot法检测上述基因的多态性,最后用测序法佐证检测结果的准确性。结果ApoAI-75Msp1、ApoE基因在乙型肝炎血清标志物不同模式之间差异有统计学意义（P〈0．05）,ApoCIII-Sst1、ApoB．Msp1、LRP5基因则差异无统计学意义（P〉0．05）。结论ApoAI-75Msp1、ApoE基因多态性与乙型肝炎血清标志物不同模式有相关性,ApoCIII-Sstl、ApoB—Msp1、LRP5与乙型肝炎血清标志物不同模式无相关性。     

Association between polymorphisms in serotonin 2C receptor gene and attention-deficit/hyperactivity disorder in Han Chinese subjects

Attention deficit hyperactivity disorder (ADHD) is much more frequent in males than females, so several genes on the X chromosome (e.g., MAOA and MAOB) have been pursued as candidates for influencing risk for the disorder. HTR2C is also located on the X chromosome. In the current study, we examined the relationship between the C-759T and G-697C polymorphisms of HTR2C and ADHD in 488 Han Chinese families. Transmission Disequilibrium Test (TDT) analysis showed that the -759C allele, the -697G allele, and haplotype -759C/-697G were significantly over-transmitted to affected probands, while haplotypes -759C/-697C and -759T/-697C were under-transmitted. When families were divided into three subtypes according to the diagnosis of probands, the -697G allele and haplotype -759C/-697G were significantly over transmitted to ADHD-C probands, while haplotype -759T/-697C was under-transmitted to these individuals; however, no biased transmission of any allele or haplotype was observed for probands with ADHD-I, suggesting that different subtypes of ADHD have different genetic influences. Our findings highlight the need to explore the role of 5-HT2C receptor dysfunction in the pathogenesis of ADHD.     

Association between tumour necrosis factor gene polymorphisms and the clinical types of patients with chronic hepatitis B virus infection

A PCR restriction fragment length polymorphism assay was used to analyse single-nucleotide polymorphisms in the tumour necrosis factor (TNF)-alpha and TNF-beta genes of 56 patients with chronic severe hepatitis B virus (HBV) infection, 71 patients who either had chronic mild HBV infection or who were asymptomatic carriers, and 90 healthy controls. The serum TNF-alpha concentrations in patients with chronic severe HBV infection were compared to those of 30 healthy controls by radioimmunoassay. The frequencies of the TNF1/2 genotype and the TNF2 allele were greater in patients with chronic severe HBV infection than in healthy controls (25% vs. 11.1%, p 0.015; 12.5% vs. 5.6%, p 0.036, respectively) and patients with chronic mild HBV infection and asymptomatic carriers (25% vs. 8.8%, p 0.011; 12.5% vs. 4.2%, p 0.015, respectively). Heterozygotes carrying the TNF2 allele had higher levels of serum TNF-alpha than homozygotes for the wild-type allele among all patients with chronic severe HBV infection (p <0.01). The genotype distribution and allele frequency of TNF-beta were similar for patients with chronic severe HBV infection and healthy controls, but the frequency of the TNF-beta*2/2 genotype in patients with chronic mild HBV infection and asymptomatic controls was lower than for healthy controls (9.9% vs. 22.4%, p 0.043) or patients with chronic severe HBV infection (9.9% vs. 26.8%, p 0.043), although this was not significant after correction for multiple testing. It was concluded that TNF-alpha gene polymorphisms may play an important role as a host factor in the progression of HBV infection.     

TIM3 gene polymorphisms in patients with chronic hepatitis B virus infection: impact on disease susceptibility and hepatocellular carcinoma traits

Hepatitis B virus (HBV) infection is associated with the development of acute and chronic liver diseases including hepatocellular carcinoma (HCC). T-cell immunoglobulin domain and mucin domain-containing molecule-3 (Tim-3), which negatively regulates T-cell response and mediates phagocytosis of apoptotic cells, has been implicated in HBV infection and cancers. This study explored the polymorphisms of TIM3 gene in 535 patients with HBV-related liver diseases including 213 chronic hepatitis, 178 cirrhosis and 144 HCC, 72 HBV infection resolvers and 182 healthy controls and analyzed the effects of these polymorphisms on the disease susceptibility and HCC traits. TIM3-1541C/T, -1516G/T, -882C/T, -574G/T and +4259T/G polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism. Of the five polymorphisms genotyped, the allele T-containing genotypes (GT + TT), allele T and allele T-containing haplotype (CTCGT) of -1516G/T polymorphism were more frequent in HBV patients than in controls [P = 0.005, odds ratio (OR) = 2.300, 95% confidence interval (CI): 1.294-4.088; P = 0.004, OR = 2.266, 95% CI: 1.297-3.962; and P = 0.005, OR = 2.203, 95% CI: 1.260-3.854, respectively]. The allele T-containing genotypes and allele T of -1516G/T were associated with HCC tumor grade (P = 0.023 and P = 0.017, respectively) and lymph node metastasis (P = 0.024 and P = 0.017, respectively). These findings suggest that -1516G/T polymorphism in the promoter region of TIM3 gene may affect the disease susceptibility and HCC traits associated with HBV infection, potentially supporting the role of Tim-3 in T-cell dysfunction and exhaustion involved in persistent HBV infection and HCC development.     

Interleukin-10 gene polymorphisms in association with susceptibility to chronic hepatitis C virus infection: a meta-analysis study

A relationship between chronic hepatitis C virus (HCV) infection and interleukin-10 (IL-10) gene polymorphisms has been reported with controversial results in different studies. In an effort to solve this controversy, we quantitatively summarized ten studies on this relationship by means of meta-analysis. Our analysis included ten case–control studies with 992 cases of chronic HCV infection and 1,123 controls. Analyses were performed with STATA version 9.0. The results showed that the IL-10 ?1082GG genotype significantly increased the risk for persistent HCV infection (AA vs. GG: OR = 0.680, 95% CI = 0.489?0.947, P = 0.022; AG vs. GG: OR = 0.608, 95% CI = 0.439?0.840, P = 0.003; GG vs. AG + AA: OR = 1.570, 95% CI = 1.160?2.123, P = 0.003), but no statistically significant differences were observed between cases and controls for IL-10 ?819C/T and IL-10 ?592C/A polymorphisms (P > 0.05). In conclusion, this meta-analysis suggested that the IL-10 ?1082GG genotype was associated with increased susceptibility for chronic HCV infection.