Changqing Xu

Association of interferon-gamma gene haplotype in the Chinese population with hepatitis B virus infection

In general, cytokines encoded by different genes of human genome might strongly influence host cell-mediated immune responses, which play an important role in the clearance of virus by the infected host. Interferon gamma (IFN-gamma) produced by T lymphocytes and natural killer cells plays an essential role in affecting cellular immune responses. A functional study demonstrated that two single nucleotide polymorphisms located in the IFN-gamma gene intron (at positions +874 and +2109) were involved in its transcriptional regulation. The aim of this study was to evaluate whether IFN-gamma gene polymorphisms or its haplotypes might be associated with predisposition to hepatitis B virus (HBV) infection in the Chinese population. The study included 181 cases with HBV infection and 272 gender, age-matched healthy controls. All genotyping were identified by polymerase chain reaction in association with the measurement of amplification refractory mutation system. A significant difference was observed between case and control groups. The frequency of +874A allele was significantly higher in patients than in controls (OR = 2.25, 95%CI = 1.69–2.99, P < 0.0001). However, no significant difference was found in the allelic frequencies of IFN-gamma +2109A/G between cases and controls (P > 0.05). By haplotype analysis, the frequency of haplotype AG (+874A and +2109G) revealed a significant difference in the cases in comparison to controls (P < 0.0001). Multiple logistic regression analysis showed that individuals possessing haplotype AG had an increased likelihood of HBV infection (OR = 8.14, 95%CI = 4.98–13.30). Our results suggest that haplotype AG containing +874A and +2109G may be a crucial risk factor of genetic susceptibility to HBV infection in the Chinese population.

Association of genetic polymorphisms in MDM2, PTEN and P53 with risk of esophageal squamous cell carcinoma

Genetic variations in MDM2, PTEN and P53 might be involved in cancer susceptibility. To assess the contribution of polymorphisms in these three genes to the risk of esophageal squamous cell carcinoma (ESCC) in a Chinese population, we genotyped MDM2 T309G, Del1518, PTEN rs701848, rs2735343 and P53 Arg72Pro polymorphisms using PCR-restriction fragment length polymorphism analysis in 226 ESCC cases and 226 cancer-free controls. Here we showed that the risk of ESCC was elevated in subjects with any of the variant genotypes of PTEN rs2735343 and P53 Arg72Pro polymorphisms, but not any genotype of MDM2 or PTEN rs701848. Moreover, multiplicative interactions were observed between PTEN rs2735343 and P53 Arg72Pro or smoking status on risk of ESCC. Our study firstly indicated that PTEN rs2735343 might be a susceptibility factor for ESCC and reaffirmed the role of P53 Arg72Pro in ESCC in this Chinese population, but did not replicate the positive association between MDM2 T309G and ESCC found previously.

Correlation of transforming growth factor beta-1 gene polymorphisms C-509T and T869C and the risk of gastric cancer in China.

Background and Aim:  As an important cytokine that modulate the cell cycle, the involvement of transforming growth factor beta‐1 (TGF‐β1) in carcinogenesis has been extensively studied for many years. Literatures have demonstrated that TGF‐β1 gene polymorphisms may alter the risk of various cancers, such as lung, prostate and breast. To investigate whether polymorphisms of the TGF‐β1 gene can modify the risk of gastric cancer, we conduct this hospital‐based, case‐control study.

The haplotype of the MxA gene promoter is associated with hepatitis B virus infection in a Chinese population

Background/Aim: The Myxovirus resistance protein A gene (MxA) is a key component of the innate antiviral response and has previously been shown to inhibit several viruses. This study was designed to assess whether the haplotype in the MxA promoter region was associated with hepatitis B virus (HBV) infection in a Chinese population.

Association analysis of hepatitis virus B infection with haplotypes of the TBX21 gene promoter region in the Chinese population.

Abstract Background: The T-box21 (TBX21) gene encodes the transcription factor T-bet (T-box expressed in T-cells), which influences naive T-lymphocyte development and has been implicated in the pathogenesis of many diseases. Methods: We selected 208 hepatitis B patients and 213 healthy volunteers to examine whether polymorphisms or haplotypes of the TBX21 gene promoter were associated with hepatitis B virus (HBV) infection in the Chinese population. Two polymorphisms at −1499 and −1514 located in the TBX21 promoter region were identified by the PCR-restriction fragment length polymorphism (PCR-RFLP) method. Results: Single nucleotide polymorphism (SNP) at −1499 was significantly different between HBV patients and healthy controls [p=0.003; odds ratio (OR) 3.65, 95% confidence interval (CI) 1.58–8.45]. Similarly, our results showed a significantly higher level of haplotype D (--/AC) in HBV patients compared to control subjects (p=0.005; OR 4.82, 95% CI 1.59–14.61). Conclusions: Based on our findings, it seems that genetic variations of allele −1499 and haplotype D (--/AC) within the TBX21 promoter region contribute to susceptibility to HBV infection in the Chinese population. Clin Chem Lab Med 2007;45:333–8.

Genetic polymorphisms of NAMPT related with susceptibility to esophageal Squamous cell carcinoma

BackgroundNicotinamide phosphoribosyl transferase (Nampt) plays a crucial role in tumorigenesis. The present study examines whether genetic polymorphisms of NAMPT are related to the risk of developing esophageal squamous cell carcinoma (ESCC).MethodsA total of 810 subjects were enrolled in this study, including 405 ESCC patients and 405 healthy controls. Using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), genotypes at rs61330082, rs2505568 and rs9034 of NAMPT were identified. Haplotypes were constructed using PHASE software. Multivariate logistic regression models were used to evaluate the potentiating effects of the genotypes, alleles and haplotypes on the development of ESCC.ResultsThe presence of genotypes CT and TT and allele T at rs61330082 was less frequent in ESCC cases than in controls (48.89% vs. 53.33%, P < 0.01, 95% CI: 0.33-0.68; 18.52% vs. 30.37%, P < 0.01, 95% CI: 0.22-0.50; 42.96% vs. 57.04%, P < 0.01, 95% CI: 0.38-0.61; respectively). No statistically significant differences existed in the distributions of genotypes or alleles at rs2505568 or rs9034 between ESCC cases and controls. Of five haplotypes constructed, haplotypes CTC, CTT and CAC were higher in ESCC cases (P < 0.01, OR = 1.57, 95% CI: 1.16-2.12; P = 0.04, OR = 1.72, 95% CI: 1.03-2.85; P < 0.01, OR = 3.39, 95% CI: 1.99-5.75; respectively) than in controls.ConclusionGenetic polymorphisms of NAMPT, specifically genotype CC and allele C at rs61330082 as well as haplotypes CTC, CTT and CAC, were significantly correlated with ESCC susceptibility.

Equivocal Association of RAD51 Polymorphisms with Risk of Esophageal Squamous Cell Carcinoma in a Chinese Population

AIM To study the contribution of genetic variation in RAD51 to risk of esophageal squamous cell carcinoma (ESCC). METHODS Three single nucleotide polymorphisms (SNPs) in RAD51 (rs1801320, rs4144242 and rs4417527) were genotyped in 316 ESCC patients and 316 healthy controls in Anyang area of China using PCR- RFLP (polymerase chain reaction-restriction fragment length polymorphism). Demographic variables between cases and controls were statistically compared by T test and Chi-square test. Hardy-Weinberg equilibrium was evaluated by the Chi-square test. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to measure any association with ESCC. Haplotype frequencies were estimated by Phase 2.1. RESULT The genotype frequencies of rs1801320, rs4144242 and rs4417527 in patients with ESCC demonstrated no significant differences from those in control group (P>0.05). When the haplotypes of these three SNPs were constructed and their relationships with ESCC risk investigated, however, CGG was observed to increase the risk (P=0.020, OR=2. 289). CONCLUSIONS There was no association between the three SNPs of RAD51 and ESCC susceptibility in our Chinese population. However, the CGG haplotype might be a risk factor.

Association between gastric cancer and -1993 polymorphism of TBX21 gene

AIM To investigate the association between the polymorphism of TBX21 gene and the risk of gastric cancer in a Chinese population. METHODS The -1993 polymorphism located in TBX21 gene promoter region was identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The risk between TBX21 gene genotype and gastric cancer was determined by multivariate logistic regression analysis in 220 gastric cancer patients and 262 cancer-free controls matched by age, sex and ethnicity. RESULTS Compared with the TBX21 -1993TT genotype, the -1993CC genotype exhibited a significantly elevated risk for gastric cancer [Odds ratio (OR) = 3.42, 95% confidence interval (CI): 1.41-8.31]. The relationship between the -1993 polymorphic genotype and the invasive status such as lymph node and distant metastasis was found among the gastric cancer patients (OR = 4.02, 95% CI: 1.87-8.66; OR = 7.02, 95% CI: 3.44-14.34, respectively). CONCLUSION TBX21 -1993 polymorphism might contribute to the risk of gastric cancer, especially to the distant metastasis.