Association between survivin promoter -31C/G polymorphism and genetic susceptibility to sporadic colorectal cancer

AIM: To investigate the association between -31C/G polymorphism in the promoter of survivin gene and the susceptibility to sporadic colorectal cancer (CRC) in southern Chinese population. METHODS: survivin -31C/G genotypes were determined by PCR-RFLP in 711 healthy controls and 702 CRC cases. RESULTS: The number of CRC patients carrying with CC genotype was much higher than that of controls (36.5 % vs 26.2%,2 =17.89,P<0.01). Compared to CC genotypes, CG, GG genotypes and G allele carriers had a significantly decreased risk of CRC, with the decrease being 0.61-fold (95% confidence interval=0.46-0.80, P<0.01), 0.52-fold (95% confidence interval=0.38-0.71,P<0.01) and 0.58-fold (95% confidence interval=0.45-0.74, P<0.01), respectively. CONCLUSION: survivin gene -31C/G polymorphism is associated with sporadic CRC risk, the G variant genotype is the independent protective factors against sporadic CRC in southern Chinese population.     

HLA-DRB1 genotyping and its relation with chronic HBV infection in patients

AIM: To study the HLA-DRB1 genotype and their relation with HBV infection in Shaanxi Han patients. METHODS: HLA-DRB1 genotyping was conducted in 108 case of chronic HBV infection and 108 health controls as well as 32 asymtomatic HBsAg carriers by using polymerase chain reaction-sequence specific primer method. All the patients, asymtomatic HBsAg carriers and health subjects were residents of Shaanxi district and belonged to Han nationality. The association between HLA-DRB1 genotype and different replication of HBV was also studied. RESULTS: DRB1*04, DRB1*09, DRB1*12 and DRB1*15 were the most common genotypes in Shaanxi Han residents with the frequency of 16.2%, 12.5%, 11.6% and 13.4%, respectively. Compared to 108 health controls, the allele frequency of HLA-DRB1*03 (10.6% of HBV patients versus 3.7% of health controls, odds ratio=3.10; P<0.05) and HLA-DRB1*07 (17.6% of HBV patients versus 9.3% of health controls, odd ratio=2.09; P<0.05) were markedly higher. The allele frequency of HLA-DRB1*15 (13.4% of HBV patients versus 6.9% of health controls, odds ratio=0.48; P<0.05) was obviously lower than than in HBV patients. CONCLUSION: HLA-DRB1*03 and HLA-DRB1*07 are closely related with susceptibility to chronic hepatitis B infection, and DRB1*15 is closely related with resistance to chronic hepatitis B infection. These finding suggest that host HLA class II gene is an important factor determining the outcome of HBV infection.     

Association of Pro12Ala polymorphism in the peroxisome proliferator-activated receptor-gamma2 with gastric cancers in China

AIM: To study the relationship among peroxisome proliferator-activated receptor-gamma2 (PPAR γ2) gene Pro12Ala polymorphism, Helicobacter pylori (H. pylori) infection, and gastric cancer in China.METHODS: 104 consecutive patients with gastric cancer and 104 age-and sex-matched controls from Guangdong Province of southern China were examined. PPARγ2 Pro12Ala polymorphism was analyzed by PCR-restriction fragment length polymorphism method (PCR-RFLP). H. pylori status of subjects was determined by enzyme-linked immunosorbent assay (ELISA) for anti-H. pylori IgG. RESULTS: The prevalence of H. pylori infection was significantly higher in gastric cancer patients than that in control (81.7% vs 59.6%, 2=12.27, P<0.01; OR=3.0, 95% CI=1.6-5.7). The CC, CG and GG genotype frequency of PPARγ2 gene in Chinese common people was 91.3%, 8.7%, 0 and the G allele frequency was 4.3%. The frequency of PPARγ2 G (Ala12) allele was significantly higher among patients with gastric cancer (19.2%) than that in control subjects (8.7%; P<0.05, OR=2.5, 95% CI=1.1-5.8). Moreover, the combination of PPARγ2 G allele and H. pylori infection substantially increased the risk of gastric cancer (P<0.01, OR=8.9, 95% CI=2.2-35.7). CONCLUSION: PPARγ2 G allele is associated with gastric cancer in China. The risk of developing gastric cancer is significantly increased in the PPARγ2 G allele carriers with H. pylori infection.     

Interaction of polymorphisms in resistin gene promoter -420C/G,cytochromes P4501A1 gene MspI and cigarette smoking on nonalcoholic fatty liver disease

AIM: To investigate the interaction of polymorphisms of resistin gene promoter -420C/G, cytochromes P4501A1-MspI and cigarette smoking in nonalcoholic fatty liver disease (NAFLD). METHODS: The genetic polymorphisms in resistin gene promoter -420C/G and CYP1A1-MspI were analyzed by the technique of polymerase chain reaction (PCR) in peripheral blood leukocytes of 900 NAFLD cases and 900 healthy persons. RESULTS: The frequencies of -420C/G (GG) and CYP1A1-MspI (m2/m2) were 49.75% and 50.08% in NAFLD cases and 24.00% and 24.25% in healthy controls, respectively. Statistical tests showed a significant difference in the frequencies between the 2 groups (P<0.01). The risk of NAFLD with -420C/G (GG) was significantly higher than that of controls. Individuals who carried with CYP1A1-MspI (m2/m2) had a high risk of NAFLD. Combined analysis of the polymorphisms showed that the percentages of -420C/G (GG)/CYP1A1-MspI (m2/m2) in NAFLD and control groups were 39.83% and 12.83%, respectively (P<0.01). The people who carried with -420C/G (GG)/CYP1A1-MspI(m2/m2) had a high risk in NAFLD group. The cigarette smoking rate in NAFLD group was signi-ficantly higher than that in control group (P<0.01), and the statistic analysis suggested an interaction between cigarette smoking and -420C/G (GG) and CYP1A1-MspI (m2/m2), which increased the risk of NAFLD.CONCLUSION: -420C/G (GG), CYP1A1-MspI (m2/m2) and cigarette smoking are the risk factors in NAFLD. The interactions between genetic polymorphisms in -420C/G, CYP1A1- MspI (m2/m2) and cigarette smoking increase the risk of NAFLD.     

Association between ERK5 -322G/T polymorphism and genetic susceptibility to sporadic colorectal cancer

AIM: To investigate the correlation between extracellular signal-regulated kinase 5 ( ERK5 ) -322G/T polymorphism (rs3866958) and the susceptibility to sporadic colorectal cancer (CRC) in southern Chinese population. METHODS: ERK5 -322G/T genotypes were determined by Taqman-MGB probes in 835 CRC cases and 908 healthy controls. RESULTS: No significance of ERK5 -322G/T genotype distribution between CRC patients and controls was observed, but -322G/T decreased the susceptibility to CRC in fat people whose BMI was ≥ 24 kg/m². Compared to GG genotypes, the carriers with GT and TT genotypes had a significant decrease in the risk of CRC(OR=0.576,95%CI 0.413-0.804, P<0.01). CONCLUSION: ERK5 -322G/T polymorphism (rs3866958) has no significant relevance with sporadic CRC susceptibility, but decrease, the risk of CRC in people with fatness. The T variant genotype is an independent protective factor against sporadic CRC of overweight patients in southern Chinese population.     

Distribution characteristics of polymorphisms of interleukin-22 gene in Guangxi population and their association with serum lipid levels

AIM: To investigate the distribution characteristics of interleukin-22 (IL-22) gene rs2227485C/T and rs2227491A/G polymorphisms in Guangxi people and the distribution differences with other ethnic groups, and to explore the difference levels of common lipid indexes in different genotypes. METHODS: SNaPshot technique and DNA sequencing were used in 280 Guangxi persons to examine IL-22 genotypes and to analyzed the distribution frequencies of allele and genotype in these sites. The distribution frequencies in different sexes, and the differences between groups and diffe-rence levels of common lipid indexes in different genotypes were analyzed statistically. RESULTS: Three genotypes of CC, CT and TT were found in rs2227485C/T with the frequency distribution of 17.1%, 49.3% and 33.6%, respectively. No significant difference between different sexes of each genotype and allele frequency in the Guangxi population was observed (P>0.05). Compared with the distribution frequencies of genotype and allele in HapMap-TSI, HapMap-HCB, HapMap-JPT and HapMap-MEX, those in Guangxi population showed statistically significant differences (P<0.05). Three genotypes of AA, AG and GG were found in rs2227491A/G with the frequency distribution of 16.1%, 52.8% and 31.1%, respectively. There was no significant difference between different sexes of each genotype and allele frequency in the Guangxi population (P>0.05). The significant differences of genotype frequencies among Guangxi population, HapMap-TSI, HapMap-JPT and HapMap-MEX were detected (P<0.05). Compared with the other 4 populations, allele frequencies in Guangxi population had significant difference (P <0.05). There were significant differences in the levels of HDL-C and LDL-C among the 3 genotypes of rs2227491A/G. The level of HDL-C had difference between AG/AA genotype and GG genotype. In addition, the level of LDL-C had difference between AG/GG genotype and AA genotype (P<0.05). CONCLUSION: rs2227485C/T and rs2227491A/G polymorphisms of IL-22 gene have differences in different populations. The rs2227491A/G polymorphism may be associated with serum lipid levels.     

Effects of ethanol on HBV gene mutations in patients with chronic hepatitis B by gene chip

AIM: To study ethanol influence on gene mutations of HBV DNA and to offer testimony for clinical diagnosis and treatment of chronic hepatitis B. METHODS: 85 patients with chronic hepatitis B were divided into alcoholic group and non-alcoholic group. Gene chip technique was used to detect gene mutations located in Pre-C nt G1896A and nt A1814C, basal core promoter (BCP) nt A1762T and nt G1764A, P nt C528A and nt T552C. RESULTS: The mutation frequency on BCP nt A1762T and nt G1764A in alcoholic group was significantly higher than that in non-alcoholic group (P<0.05). No difference of mutation frequency on pre-c nt G1896A nt A1814C and P nt C528A nt T552C between alcoholic and non-alcoholic group was observed (P>0.05). CONCLUSION: Ethanol stimulates HBV gene mutations on BCP nt A1762T and nt G1764A, enhances HBV DNA replication and gene expression, deteriorates the state of the illness.     

Study on the association of the polymorphism at the position -418A/G and -384C/T in the Apo(a) promoter

AIM: To investigate two single nucleotide polymorphisms (SNP) in the apolipoprotein(a) promoter at positions -418 and -384 and to compare distributing difference of genotype frequencies of single nucleotide among different races and to explore the influencies of them on serum lipid level and their association with coronary heart disease (CHD). METHODS: Using PCR-RFLP (BsgI,BfaI) method, we determined genotypes of these two SNPs in 156 unrelated healthy controls of HanZu Chinese and 56 unrelated CHD patients of HanZu Chinese and 56 unrelated African Blacks, then cloned polymerase chain reaction (PCR) products into T-vector and sequenced it by M13 currency primer, correspondingly. RESULTS: (1) There was no polymorphism at position -418A/A and -384C/C in control group. Only one CHD patient's genotype determined was -418G/G, other were -418A/A and -384C/C in CHD patients. (2) Only two African Blacks' genotype determined was -418G/G, other were -418A/A and -384C/C in African Blacks. (3) However, the Apo(a) promoter sequence was in coincident with the sequence publicized in GenBank and the base at positions -418 was adenine (A) and -384 was cytosine (C). CONCLUSION: The mutation frequencies at position -418 and -384 were low in the Chinese Han Population of Hubei and perhaps no single nucleotide polymorphisms was at two positions. No association with serum lipid levels and CHD was observed. There were great variabilities to the SNPs in the Apo(a) promoter among different races.     

The levels of 2′, 5′ oligoadenylate synthetase,interleukin 2 and interleukin 12 in hepatitis B virus infection

AIM: In order to study the effect of endogenous interferon system and Th1 response modes on hepatitis B virus infection, the 2′, 5′ oligoadenylate synthetase (2-5OAS), IL-2 and IL-12 were selected as the research parameters. METHODS: The activity of 2-5OAS in peripheral blood mononeuclear cells was determined by sensitive radioenzymatic assay. IL-2 and IL-12 were determined by ELISA. RESULTS: Compared to normal control, the 2-5OAS, IL-2 or IL-12 were not significantly changed (P>0.05) in the asymptomatic HBsAg carricer group. The 2-5OAS, IL-2 and IL-12 were significantly up-regulated (P<0.01) in the group of acute hepatitis, but in the groups of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma, the 2-5OAS, IL-2, IL-12 were significantly down-regulated (P<0.05). Moreover, with the progression of patient′s conditions and with the complications of liver cirrhosis and hepatocellular carcinoma, the 2-5OAS, IL-2 and IL-12 decreased progressively, the 2-5OAS, IL-2, IL-12 were the lowest in guoups of liver cirrhosis and hepatocellular carcinoma (vs each groups of chronic hepatitis, P<0.05). CONCLUSION: The endogenous interferon system and Th1 response are significantly alterable in the different period of hepatitis B virus infection and among the different clinical types. The cellular immunity plays an important role in recovery from HBV infection.     

Correlation of adiponectin gene SNP+45 T/G polymorphism with coronary heart disease

AIM: To investigate the relationship between adiponectin gene SNP+45 polymorphism and coronary heart disease (CHD) in south China Han population. METHODS: The nondiabetic CHD patients diagnosed by the coronary angiography were selected as CHD subjects (153 cases), and 73 healthy adults served as normal control subjects. The polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) was performed to identify the distribution pattern of adiponectin gene SNP+45 in all subjects. The levels of plasma adiponectin were measured by ELISA. RESULTS: The frequency of T/G + G/G genotype and G allele in CHD patients were significantly higher than those in control subjects (P<0.05). Logistic regression analysis revealed that the adiponectin gene SNP+45 T/G+G/G genotype had a strong positive association with CHD (OR: 2.132, 95.0% CI: 1.034-4.397, P＜0.05). The plasma adiponectin was negatively associated with CHD (OR: 0.868, 95.0% CI: 0.785-0.959, P<0.05). CONCLUSION: The T/G+ G/G genotype was a possible risk factor for CHD in southern China Han population.     

Association of IFN-γ and IL-4 gene polymorphisms with childhood bronchial asthmatic susceptibility and the levels of plasma IFN-γ,IL-4 and IgE

AIM: To investigate the gene polymorphisms of interferon-γ(IFN-γ) and interleukin-4(IL-4) and the association with asthmatic susceptibility and the levels of plasma IFN-γ, IL-4 and IgE of asthmatic children. METHODS: 100 asthmatic children and 122 control children were enrolled the study. The genotypes of IFN-γ gene-179G/T polymorphism, IL-4 gene-33C/T and-589C/T polymorphisms were tested by PCR-RFLP.The genotype of IFN-γ gene +874A/T polymorphism was tested by AS-PCR.The CA repeat polymorphism of IFN-γ gene was detected by capillary electrophoresis technique.The levels of serum IFN-γ, IL-4 and IgE were measured by ELISA. RESULTS: 100 asthmatic children and 122 control children were all GG homozygotes at -179 locus of IFN-γ gene.-179 locus of IFN-γ gene has no mutation. The genotypes and allele frequency of IFN-γ gene +874A/T and CA repeat polymorphisms showed no significant difference between asthmatic children and the control(P>0.05). An association was revealed between IFN-γ gene +874A/T polymorphism and the level of plasma IFN-γ.The level of IFN-γ was lower in AA genotype than in AT genotype(P<0.05). The genotypes and allele frequency of IL-4 gene -33C/T and -589C/T polymorphisms showed significant difference between asthmatic children and the control(P<0.05).The levels of plasma IL-4 and IgE were higher in TT genotype at -33 locus and -589 locus than those in CT genotype, but only -33C/T polymorphism was associated with the level of plasma IL-4(P<0.05). CONCLUSION: The IFN-γ gene +874A/T and CA repeat polymorphisms were not correlated with asthmatic susceptibility, but there is significant correlation between the level of IFN-γ and +874A/T polymorphism. TT genotype of IL-4 gene -33 locus and -589 locus maybe the susceptible genotype of asthma in children, and the -33 locus polymorphism is associated with the level of IL-4.     

Effect of hepatitis virus B protein on the functions of PBMCs isolated from patients with chronic HBV infection

AIM: To study the effect of hepatitis virus B proteins on peripheral blood mononuclear cells (PBMCs) from patients among various types of chronic hepatitis B virus (HBV) infection.METHODS: 80 patients of various types of chronic HBV infection were observed, including 40 HBeAg positive with abnormal alanine aminotransferase (ALT) (A group), 20 HBeAg positive with persistent normal ALT(B group), 20 HBeAg and HBV-DNA negative with persistent normal ALT level(C group). IL-10, IFN-γ in CD8+CD28+T cells, after stimulation with PHA, HBeAg and HBcAg for 48 h, were inspected respectively in PBMCs.RESULTS: IFN-γ was significantly lower in HBeAg positive patients. IL-10 was significantly higher in HBeAg positive with normal ALT. CD8+CD28+T were significantly lower than others. CONCLUSION: In HBeAg positive group, secretion of cytotoxic T lymphocyte (CTL) and Th1 type cellular immunologic reaction is decreased, Th2 type cellular immunologic reaction is enhanced.     

Interaction of polymorphisms of ICAM-1 gene K469E and MCP-1 gene -2518A/G in invasion and metastasis of gastric carcinoma

AIM: To investigate the interaction of polymorphisms of intercellular adhesion molecule-1 (ICAM-1) gene K469E and monocyte chemoattractant protein-1 (MCP-1) gene -2518A/G in the invasion and metastasis of gastric carcinoma. METHODS: Based on TNM classification, 4 500 patients with confirmed gastric carcinoma from the First Affiliated Hospital of Xinxiang Medical University in China from December 2009 to November 2014 were divided into stageⅠ group, stage Ⅱgroup, stage Ⅲ group, stage Ⅳ group, and stage 0 group, with 900 cases in each group. No significant difference among the 5 groups in age, gender, ethnicity, birthplace and living habit was observed. The genetic polymorphisms of ICAM-1 gene K469E and MCP-1 gene -2518A/G were analyzed by the technique of polymorphism-polymerase chain reaction (PCR) in peripheral blood leukocytes of above-mentioned cases. RESULTS: Statistical tests showed signi-ficant differences in the frequencies of K469E (EE) and -2518A/G (GG) among each group (P<0.01). The risk of the invasion and metastasis of gastric carcinoma significantly increased in subjects with K469E (EE) genotype and in those with -2518A/G (GG) genotype. Combined analysis of the polymorphisms showed that distribution frequency of K469E (EE)/-2518A/G (GG) in stage Ⅰ group, stage Ⅱ group, stage Ⅲ group, stage Ⅳ group and stage 0 group was 39.22%, 53.22%, 59.22, 65.44% and 12.11%, respectively (P<0.01). The people who carried with K469E (EE)/-2518A/G (GG) had a high risk of the invasion and metastasis of gastric carcinoma, and statistical analysis suggested a positive interaction in a super-multiplicative model between K469E (EE) and -2518A/G (GG) in increasing the risk of the invasion and metastasis of gastric carcinoma. CONCLUSION: ICAM-1 gene K469E (EE) and MCP-1 gene -2518A/G (GG) are the risk factors in the invasion and metastasis of gastric carcinoma, and significant interactions between genetic polymorphisms of K469E and -2518A/G added the risk of the invasion and metastasis of gastric carcinoma.     

Relationship between single nucleotide polymorphism -229C/T in P1 promoter of furin gene and functions of hepatocytes in patients with liver cirrhosis

AIM: To study the influences of P1 promoter activity of furin gene on the functions of hepatocytes in patients with liver cirrhosis. METHODS: The patients with liver cirrhosis of 180 cases were recruited. The single nucleotide polymorphism (SNP -229 C/T) in P1 promoter of furin gene was genotyped using competitively differentiated polymerase chain reaction. The relationships between the promoter activity based on genotyping and the serum levels of liver enzymes, total bilirubin, albumin and prothrombin were observed. RESULTS: The distribution frequencies of allele C and T were 75.3% (271/360) and 24.7% (89/360). Those of genotypes CC, CT and TT were 62.2% (112/180), 26.1% (47/180) and 11.7% (21/180), respectively. The distribution frequencies of the genotypes were not related to the serum levels of major liver enzymes, albumin, total bilirubin and prothrombin, except for alkaline phosphatase and γ-glutamyl transferase. CONCLUSION: The activity of furin promoter exerts no effects on the main functions of hepatocytes, suggesting that furin may be a new therapeutic target for HBV infection.     

Correlation between clinical stages of HBV chronic infection and co-expression of CD244 and PD-1 in HBV-specific CTLs

AIM: To investigate the co-expression of cluster of differentiation 244 (CD244) and programmed death 1 protein (PD-1) on hepatitis B virus (HBV) antigen-specific cytotoxic T-lymphocytes (CTLs) in chronic hepatitis B (CHB) patients and its correlation with the clinical stages of HBV chronic infection. METHODS: Eighty-one CHB subjects with human leukocyte antigen-A2 (HLA-A2) positive, including 20 cases of acute-on-chronic liver failure (ACLF), 20 cases of severe chronic hepatitis B (s-CHB), 34 cases of mild and moderate chronic hepatitis B (m-CHB) and 7 cases of immune tolerant stage (IT) of chronic hepatitis B as well as 14 healthy controls (HC), were enrolled in this study. The co-expression of CD244 and PD-1 was analyzed in virus-specific CD8⁺ T-cells derived from peripheral blood using major histocompatibility complex class I (MHC-I) pentamers targeting immunodominant epitopes of HBV core antigen (18-27). RESULTS: In the patients with chronic HBV infection, virus-specific CD8+T-cells with co-expression of CD244 and PD-1 were at increased levels than those in total CD8+ T-cells (67.48%±17.16% vs 14.01%±7.97%, P<0.01) in the peripheral blood. Among different clinical stages, increased level of CD244 expression coincided with increased expression of PD-1 in m-CHB compared with IT of CHB (73.08%±8.63% vs 53.11%±18.05%, P<0.05), which was followed by decreased co-expression level in ACLF (63.11%±13.87% vs 72.05%±16.86%, P<0.05) and restoration of the ability to secrete IFN-γ (30.95%±20.29% vs 13.63%±10.46%, P<0.05). CONCLUSION: CD244 and PD-1 are highly co-expressed in HBV-specific CTLs in the patients with s-CHB and m-CHB, and are decreased in ACLF following the restoration of IFN-γ secretion. The severity of CHB may be correlated with CD244 and PD-1 co-expression in HBV-specific CTLs.     

Serum lipid levels and ApoB gene Xba I and 3'-VNTR polymorphisms in longevous elderly Han population in Zhejiang

AIM: To study the levels of serum lipids and the effects of apolipoprotein B (ApoB) gene Xba I-restriction fragment length polymorphism (RFLP) and 3'-variable-number tandem repeat (VNTR) polymorphism on serum lipid and apolipoprotein levels in longevous elderly Han population in Zhejiang. METHODS: Physical and laboratory examinations were performed on longevous elders, children of longevous elders, normal control people and children of non-longevous elders, and the Xba I-RFLP and 3'-VNTR polymorphism in ApoB gene were genotyped. RESULTS: The serum levels of triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and ApoB were negatively correlated with longevity (P<0.05), while the level of high-density lipoprotein cholesterol (HDL-C) was positively correlated with longevity (P<0.01). The levels of total cholesterol (TC), LDL-C and ApoB were higher and the HDL-C level was lower in the people with Xba I-RFLP X⁺X^- genotype than those in the people with Xba I-RFLP X^-X^- genotype (P<0.01). The levels of TC, TG, LDL-C and ApoB were higher and the HDL-C level was lower in the people with 3'-VNTR large allele than those in the people with 3'-VNTR minor allele (P<0.01). CONCLUSION: High TG, LDL-C and ApoB levels and low HDL-C level are not conductive to longevity. Serum lipid levels in the people with Xba I-RFLP X^-X^- genotype or 3'-VNTR minor allele are healthy and conductive to longevity.     

Correlation between DDAH2 gene polymorphism and coronary heart disease

AIM: To investigate the relationship between single nucleotide polymorphism (SNP) of dimethylarginine dimethylamino acid hydrolase (DDAH) gene and coronary heart disease (CHD) in Chinese population. METHODS: The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and ligase detection reaction (LDR) were used to detect the genotypes of SNP rs805305 and rs2272592 in 192 controls and 165 patients with coronary heart disease (CHD). RESULTS: Both the frequency of rs805305 CG+GG or G allele and the frequency of rs2272592 GA+AA or A allele had no significant difference between CHD and control (P＞0.05). These results were independent of age, gender, hypertension, diabetes and hyperlipidemia. CONCLUSION: The rs805305 and rs2272592 polymorphism of DDAH2 gene might not be related to the coronary heart disease (CHD) in Chinese.     

Association of OPG gene single nucleotide polymorphisms with susceptibility to rheumatoid arthritis in Chinese Han population

AIM：To investigate the association of osteoprotegerin (OPG) gene single nucleotide polymorphisms (SNPs), 163A/G (rs3102735) and 245T/G (rs3134069), with susceptibility to rheumatoid arthritis (RA) in Chinese Han population. METHODS：A total of 205 patients with RA and 171 healthy control subjects were enrolled into this study. Genotyping was performed by polymerase chain reaction-based restriction fragment length polymorphism and subsequently confirmed by DNA sequencing. Odds ratio (OR) and 95% confidence intervals (CI) were calculated for the risk genotypes and alleles. RESULTS：OPG gene polymorphisms 163A/G and 245T/G were conformed to the Hardy-Weinberg equilibrium. The statistical differences in the genotypes of AA, AG and GG at 163A/G locus were found in RA and controls. The G allele was associated with an increased risk of RA, with OR of 1.219 (95％ CI: 1.066~2.339). No significant difference was observed between RA group and control group with respect to genotypic and allelic frequencies of OPG gene 245T/G (P>0.05）. CONCLUSION：The OPG gene 163A/G SNP may be associated with RA susceptibility, and G allele may be the risk factor for developing RA.     

Relationship between precore/basal core promoter mutations of hepatitis B virus and therapeutic effect of peginterferon α-2b,and changes of mutations before and after treatment

AIM:To investigate the relationship between therapeutic effect of peginterferon α-2b (Peg-IFNα-2b) and precore (PC) region G1896A and basal core promoter (BCP) region A1762T/G1764A mutations of hepatitis B virus (HBV), and the changes of the mutations before and after treatment. METHODS:The patients with HBeAg-positive chronic hepatitis B (CHB) (n=69) were treated with Peg-IFNα-2b for 48 weeks and followed up for 24 weeks. The PC and BCP sequences at baseline and the 72th week were determined using polymerase chain reaction (PCR) and direct sequencing. Serum HBsAg, HBeAg, alanine aminotransferase (ALT) and HBV DNA was quantified in the samples taken at baseline (week 0), during the treatment period (weeks 4, 8, 12, 24, 36 and 48), and during follow-up (weeks 60 and 72). RESULTS:Within the total cohort, wild-type (WT) virus was detectable in only 14 patients (20.29%), and mutants were detected in 55 patients (79.71%). The serum HBeAg level in the patients with mutant virus was significantly lower than that in the patients with WT virus (P=0.024). The proportion of WT, PC mutant, BCP mutant and PC+BCP mutant was significantly changed at baseline and week 72 (P=0.004). No significant difference of HBeAg seroconversion and combined response between patients with WT virus or mutants (PC, BCP and PC+BCP) was observed. CONCLUSION:PC and BCP mutations have no effect on the response of HBeAg-positive CHB patients to Peg-IFNα-2b. The proportion of each mutation was significantly changed before and after treatment.     

Investigating the correlation between MTDH/AEG-1 gene 5'-UTR polymorphism and genetic susceptibility to sporadic colorectal cancer

AIM: To assess the correlation between MTDH/AEG-1 gene 5'-UTR polymorphism and genetic susceptibility to sporadic colorectal cancer (CRC) in southern Chinese population by TaqMan-MGB fluorescence probes. METHODS: A case-control study was carried out on southern Chinese population to collect blood DNA samples (693 sporadic CRCs and 660 controls respectively) to investigate MTDH/AEG-1 gene 5'-UTR polymorphism by TaqMan-MGB probes. RESULTS: The distribution of MTDH/AEG-1 5'-UTR genotypes (-1 913C/G,-797G/A) had no significance between CRCs and controls. But GG genotype of -1 913C/G could increase the susceptibility of CRC in drinker(OR=1.71,95%CI=1.13-2.57) and female(OR=1.48, 95%CI= 1.01-2.17), -1 913GG had interaction with drinking and female gender to increase the risk of CRC( P<0.01); Mutated genotypes of -797(GA+AA) also could increase the susceptibility of CRC in drinker (OR=1.55,95%CI= 1.06-2.27) and person with family history of cancer(OR=3.48,95%CI= 1.60-7.57), -797(GA+AA) had interaction with drinking and positive family history of cancer to increase the risk of CRC( P<0.01). But both polymorphisms were not interacted with age, smoking and fatness. CONCLUSION: MTDH/AEG-1 gene 5'-UTR polymorphism has no significant relevance with sporadic CRC susceptibility, but is irrelevant with drinking, gender and family history of cancer to increase the risk of CRC.