Association of NOD1 and NOD2 genes polymorphisms with Helicobacter pylori related gastric cancer in a Chinese population

AIM:To investigate the association between the tag single nucleotide polymorphisms(TagSNPs) of NOD1 and NOD2 and the risk of developing gastric cancer.METHODS:We conducted a hospital-based case-control study including 296 incident gastric cancer patients and 160 gastritis controls.Eight TagSNPs in the NOD1 and NOD2 genes were selected from the Hapmap database using the haploview software and genotyped by the Sequenom MassArray system.The serum levels of anti-Helicobacter pylori(H.pylori) IgG were measured by enzyme-linked immunosorbent assay to indicate H.pylori infection.The odds ratios(OR) and 95% confidence intervals(CI) were calculated by unconditional logistic regression,including sex and age as confounding factors.RESULTS:The NOD1 rs2907749 GG genotype showed a decreased risk for gastric cancer(OR 0.50,95% CI:0.26-0.95,P = 0.04) while the rs7789045 TT genotype showed an increased risk(OR 2.14,95% CI:1.20-3.82,P = 0.01).An elevated susceptibility to gastric cancer was observed in the subjects with H.pylori infection and the NaOD1 rs7789045 TT genotype(OR 2.05,95% CI:1.07-3.94,P = 0.03) or the NOD2 rs7205423 GC genotype(OR 2.52,95% CI:1.05-6.04,P = 0.04).Haplotype analysis suggested that the distribution of AGT(rs2907749,rs2075820 and rs7789045) in NOD1 between the cases and control groups was significantly different(P corrected:0.04),and the diplotype AGT/AGT was associated with an elevated gastric cancer risk(OR 1.98,95% CI:1.04-3.79,P = 0.04).The association of the NOD1 rs7789045 TT genotype and the diplotype AGT/AGT was significant with H.pylori-related diffuse-type gastric cancer(OR 3.00,95% CI:1.38-6.53,P = 0.01;OR 4.02,95% CI:1.61-10.05,P < 0.01,respectively).CONCLUSION:Genetic polymorphisms in NOD1 and NOD2 may interact with H.pylori infection and may play important roles in promoting the development of gastric cancer in the Chinese population.

Association of polymorphisms of IL and CD14 genes with acute severe pancreatitis and septic shock

AIM. To investigate IL-1β＋3 594 in the 5^th intron, IL-10-1 082 and CD14-159 polymorphisms in patients with acute pancreatitis （AP） and septic shock.METHODS： The study induded 215 patients （109 with acute severe pancreatitis （SAP）, 106 with acute mild pancreatitis （MAP）） and 116 healthy volunteers. Genomic DNA was prepared from peripheral blood leukocytes. Genotypes and allele frequencies were determined in patients and healthy controls using restriction fragment length polymorphism analysis of PCR products.RESULTS： The frequencies of IL-β＋3 594T, IL-10-1082G and CD14-159T allele were similar in patients with mild or severe pancreatitis and in controls. Within SAP patients, no significant differences were found in the allele distribution examined when etiology was studied again. Patients with septic shock showed a significantly higher prevalence of IL-10-1082G allele than those without shock （X^2 = 5.921,P= 0.015）.CONCLUSION： IL-10-1082G plays an important role in the susceptibility of SAP patients to septic shock. Genetic factors are not important in determination of disease severity or susceptibility to AP.

Association of Polymorphisms in Angiotensin-converting Enzyme and Type 1 Angiotensin Ⅱ Receptor Genes with Coronary Heart Disease and the Severity of Coronary Artery Stenosis

To explore the relation of angiotensin-converting enzyme （ACE） and angiotensin Ⅱ type 1 receptor （AT1R） gene polymorphism with coronary heart disease （CHD） and the severity of coronary artery stenosis, 130 CHD patients who underwent coronary angiography were examined for the number of affected coronary vessels （≥75% stenosis） and coronary Jeopardy score. The insertion/deletion of ACE gene polymorphism and AT1R gene polymorphism （an A→C transversion at nucleotide position 1166） were detected by using polymerase chain reaction （PCR） and restriction fragment length polymorphism （RFLP） in CHD patients and 90 healthy serving as controls. The resuits showed that DD genotype and of ACE were more frequent in CHD patients than that in control group （38.5% vs 14.4%, P〈0.001）. The frequency of the ATIR A/C genotypes did not differ between the patients and the controls （10% vs 13.1%, P〉0.05）. The relative risk associated with the ACE-DD was increased by AT1R-AC genotype. Neither the number of affected coronary vessels nor the coronary score differed among the ACE I/D genotypes （P〉0.05）. But the number of affected coronary vessels and the coronary score were significantly greater in the patients with the AT1R-AC genotype than in those with the AA genotype （P〈0.05）. In conclusion, DD genotype may be risk factor for CHD and MI in Chinese people, and is not responsible for the development of the coronary artery stenosis. The AT1R-C allele may increase the relative risk associated with the ACE-DD genotype, and may be involved in the development of the stenosis of coronary artery.

Coalition of DNA polymorphisms of ApoB and ApoAI genes is related with coronary artery disease in Kazaks

Objective To explore the relationship between polymorphisms of XbaI and MspI loci of apolipoprotein B （ApoB） gene and -75 bp,＋83 bp loci of apolipoprotein AI （ApoAI） gene and coronary heart disease （CHD） in Kazaks of Xinjiang Uyghur Autonomous Region,China.Methods These loci were analyzed by PCR-restriction fragment length polymorphism （PCR-PFLP）.Two hundred and five patients with CHD and two hundred and thirty six controls were involved.Results There were significant distinctions among low-density lipoprotein cholesterol （LDL-C）,triglyceride （TG） and the ApoAI/ApoB ratio between the two groups,but no significant distinction among the polymorphism frequencies of the four sites between the two groups.The polymorphism coalition frequency of X-/Ms＋＋/M1＋-/M2＋＋ （named Coalition 11） was significantly higher in CHD compared to the control group （14.6％ vs.7.2％,P ＜ 0.05）.The level of total cholesterol （TC） in Coalition 1 1 was significantly higher and the level of the ApoAI/ApoB ratio in Coalition 11 was significantly lower than Coalition 1～10 in CHD patients.The level of the ApoAI/ApoB ratio of Coalition 11 was significantly lower than the Coalition 1～10 in control group.The levels of ApoAI/ApoB ratio of Coalition 3 were significantly higher compared to Coalition 11 in the two groups,respectively.The level of LDL-C of Coalition 3 was significantly lower than in the Coalition 11 in control group.The level of TC of Coalition 5 was significantly higher than Coalition 3 in the CHD group.The level of the ApoAI/ApoB ratio of Coalition 5 was significantly lower than in Coalition 3 or Coalition 1～10 of the two groups,respectively.The level of LDL-C of Coalition 5 was significantly higher than in Coalition 3 in control group.The ratio of ApoAI/ApoB was negatively related to TC,LDL-C and was positively related to HDL-C,both in CHD and control groups.Conclusion Coalition 11 of the 4 loci polymorphisms of the ApoB and ApoAI genes was correlated with CHD in Kazaks,and perhaps the ratio of ApoAI/ApoB was the most diagnostic parameter related with CHD among all lipid parameters.CHD may also be associated with Coalition 5,and,perhaps,Coalition 3 may have been confirmed as a protection factor against CHD,if more samples were enrolled.

Detecting the polymorphism sites of p53 and Fas genes of Han population in Zhejiang province

BACKGROUND： It is of significance for single nucleotide polymorphisms （SNPs）, a difference of rank, which exists widely in biology, genetics and other fields. OBJECTIVE： To detect polymorphism sites in exon-4 of p53 gene, promotor of Fas gene and intron-7 of Fas gene of healthy people in Han nationality in Zhejiang province. DESIGN： Simple random sampling. SETTING： Department of Surgery of the 118 Hospital of Chinese PLA.PARTICIPANTS： A total of 80 healthy people in Han nationality were selected from hospitals in Zhejiang province from August 2005 to January 2006. There were 43 males and 37 females aged from 3 to 78 years with the mean age of 39.5 years, and all subjects were consent. DNA which was used in genetic analysis was selected from peripheral venous blood of all subjects and maintained at -20℃.METHODS： Polymorphism sites in exon-4 of p53 gene, promotor of Fas gene and intron-7 of Fas gene were detected with directly DNA sequencing technique. MAIN OUTCOME MEASURES ： Polymorphism sites in exon-4 of p53 gene, promotor of Fas gene and intron-7 of Fas gene of healthy people in Han nationality in Zhejiang province. RESULTS： A total of 80 samples were involved in the final analysis. SNPs sites were found at the 119^th base of exon-4 of p53 gene （the 72^nd codon of p53 gene）, the 670^th base of upper start codon in promotor of Fas gene （Fas-670）, and the 995^th base of intron-7 of Fas gene, especially SNPs in the 995^th base of intron-7 pf Fas gene, i.e. C→A transversion, was a new site.CONCLUSION ： One unknown SNPs site is discovered in intron-7 of Fas gene of people in Han nationality in Zhejiang province. This study also proves that the 72^nd codon exists in p53 gene and the -670 polymorphism site exists in promotor of Fas gene.

The polymorphism of heat shock protein 70 genes in Chinese Han population in Fujian province

To understand the polymorphism of the heat shock protein 70 （HSPTO） genes in Chinese Han population and to explore the co-relations between HSP70 polymorphism and disease, three polymorphic loci of HSP70 genes in 127 healthy Chinese Han population in Fujian province were analyzed by PCR and restriction enzyme analysis, and the genotypes and allele frequencies of HSPTO in different populations from various area were compared. It was found that the proportions of HSPTO-1 genotypes GG, GC and CC among Chinese Han population in Fujian province were 55.1%, 40.2% and 4.7% respectively, while those of HSP70-2 genotypes AA, AG and GG were 44.1%, 48.8 % and 6.9% respectively, and those of HSP70-hom genotypes TF, TC and CC were 59.8%, 37.0% and 3.2% respectively. The allele frequencies of G and C in HSP70-1 were 75.2% and 24.8% ; those of A and G in HSP70-2 were 68.5% and 31.5% and those ofT and C in HSP70-hom were 78.3% and 21.7% respectively. The distribution of the HSPTO-1 polymorphisms in Chinese Han population was almost the same as those in Japanese and Mexican populations, but it was rather different from those of American and Spanish populations with a significant differences. Meanwhile, the frequency of GG homozygote in HSPTO- 1 was signifi- cantly higher than those in American and Spanish populations. No significant difference was found in the distribution of HSPTO-2 polymorphism between Chinese and Japanese populations, in which the differences among American, Mexican and Spanish populations were quite obvious. The frequency of AA homozygote in HSPTO-2 was significantly higher than those in Mexican, American and Spanish populations, while, the distribution of HSPTO-hom genotype and allele frequency in Chinese Han population was almost just the same as those in Japanese and Mexican populations. Furthermore, it was also found that the genotype distribution and allele frequencies of the HSPTO genes in Han population of Fujian province were almost the same as those in Han population in Taiwan, but they were different in certain loci from those of Han population in Wuhan area. It is evident that the distribution of HSPTO gene polymorphisms among Chinese Han population are different from other regions in the world.

Polymorphisms of the CAPN1, CAST and MSTN Genes,and Their Association with Histological and TexturalParameters of Beef from Polish Holstein-Friesian Cattle

The purpose of this study was to analyse polymorphisms of the CAPN1, CAST and MSTN genes and their association with the microstructure of the Musculus longissimus thoracis (MLT) and textural parameters in bulls of the Holstein-Friesian breeds, black-and-white variety. The polymorphisms at the three loci: in position 6536 of the 3’UTR region of the CAPN1 gene, in position 230 of intron 5 in CAST gene, and in position 371 of the promoter region of the MSTN gene were analysed. Given the inconsequential genetic diversity at the analysed CAPN1 and MSTN loci in the animal sample, it was considered unreasonable to perform further statistical analyses aimed at determining associations between polymorphisms in these positions and meat characteristics. Based on an analysis of the CAST gene polymorphism, a significant association with certain histological and textural parameters was identified.

Evaluation of angiotensin converting enzyme insertion/deletion, alpha adducin (ADD1) G460W, and IL-10 gene polymorphisms, and determination of prognostic effects in idiopathic sudden sensorineural hearing loss

Objective:The aim of this study was to examine angiotensin converting enzyme(ACE)insertion/deletion,alpha adducin,and interleukin-10(IL-10)gene polymorphisms(GPs)in terms of both idiopathic sudden sensorineural hearing loss(ISSNHL)risk and their potential prognostic effects.Methods:The study group consisted of 70 patients and the control group consisted of 50 patients.Venous blood samples were analyzed for relevant GPs via kompetitive allele-specific polymerase chain reaction.Age,sex,affected side,tinnitus,and vertiginous symptom status,number of days between symptom onset and hospital admission,pure tone audiometry results at admission and after treatment were included in the study.Data were compared statistically.Results:The D allele of ACE insertion/deletion GP was significantly more frequent in patients with ISSNHL than in the control group(p=0.032).II genotype was associated with a reduced risk of ISSNHL(p=0.036).The amount of hearing loss was significantly higher in patients with the TT genotype(p=0.027)and T allele of the IL-10 GP(p=0.035)than in the patients without this allele.Severe hearing loss was a poor prognostic factor(p=0.008).Conclusions:The D allele of ACE insertion/deletion GP may be involved in the ISSNHL etiology.Due to the association of this allele with occlusive vascular pathologies,ischemia is believed to be a common pathway in the etiopathogenesis of ISSNHL.

AGTR1 A1166C gene polymorphism is associated with the effectiveness of valsartan monotherapy in Chinese patients with essential hypertension:A retrospective analysis

Objective:To investigate whether angiotensinⅡtype 1 receptor(AGTR1 A1166C)gene polymorphism was associated with the effectiveness of valsartan monotherapy in Chinese patients with essential hypertension.Methods:This retrospective analysis included 198 patients(≥18 years of age)who received valsartan monotherapy(80 mg/day)for newly developed essential hypertension at the authors’center between January 1,2020 and December 31,2023.Genotyping for AGTR1 A1166C gene polymorphism was done by polymerase chain reaction(PCR)-melting curve analysis of genomic DNA from peripheral blood samples.A dominant genetic model for AGTR1 A1166C(AA genotype versus AC+CC genotype)was used.Multivariate regression analysis of baseline variables and AGTR1 polymorphism was conducted to identify predictors of target blood pressure attainment(<140/90 mmHg)at the 4-week follow-up.Results:The median age of the 198 patients was(53.7±13.5)years,and 58%were men.Genotyping assays showed that 164 patients had the AA genotype,and 34 patients were of the AC/CC genotype,including 30 with the AC genotype and 4 with the CC genotype.Allele distribution was consistent with Hardy Weinberg equilibrium.109 Patients(55.1%)attained the blood pressure target.Multivariate analysis showed that smoking(versus no smoking,HR 0.314,95%CI 0.159-0.619,P=0.001)and AGTR1 A1166C AA genotype(versus AC/CC,HR 2.927,95%CI 1.296-6.611,P=0.023)were significant and independent predictors of target attainment.25 Patients(73.5%)with AGTR1 A1166C AC/CC genotype attained the target versus 51.2%(51/164)of patients with AGTR1 A1166C AA genotype(P=0.017).Patients with AGTR1 A1166C AC/CC genotype had a significantly greater reduction in systolic blood pressure[(33.1±10.8)mmHg versus(29.2±11.7)mmHg in AA carriers;(P=0.029)].Conclusions:Hypertensive patients carrying one or two C alleles of the AGTR1 A1166C gene were more responsive to valsartan treatment.

Distribution of gene polymorphisms associated with aspirin antiplatelet in the Han NSTEMI population

Objective:To analyze the genotype and allele distribution characteristics of GPⅢa PLA2(rs5918),PEAR1(rs12041331),and PTGS1(rs10306114)genes related to the antiplatelet pharmacological effects of aspirin,providing reference for individualized treatment of Chinese Han NSTEMI patients.Methods:A total of 107 Han patients with NSTEMI in Beijing Luhe Hospital affiliated to Capital Medical University from January 2016 to December 2022 were selected as the research subjects.The genotypes of GPⅢa PLA2(rs5918),PEAR1(rs12041331)and PTGS1(rs10306114)were detected by fluorescence staining in situ hybridization.The frequency distribution and allele distribution of genotype were analyzed.The results were analyzed whether there were statistical differences in the distribution of related alleles between the Han NSTEMI population and some populations in the 1000 Genomes database.Results:In the Han NSTEMI population,the genotype frequencies of GPⅢa PLA2(rs5918)locus were TT 97.20%,TC 2.80%and CC 0%,the allele frequencies were T 98.60%and C 1.40%.The genotype frequencies of PEAR1(rs12041331)locus were GG 42.06%,GA 44.86%and AA 13.08%,the allele frequencies were G 64.49%and A 35.51%.The genotypes at the PTGS1(rs10306114)locus were all AA(100%),no AG or GG genotype was found.Conclusion:In the NSTEMI population of Han nationality,the mutation at GPⅢa PLA2(rs5918)site related to aspirin antiplatelet pharmacology is rare,and there is no mutation at PTGS1(rs10306114)site.Wild homozygotes are dominant in these two gene loci,while mutations in PEAR1(rs12041331)are more common.Some of the findings in this study are similar to those in previous reports or other populations included in the relevant database;however,some results differ from previous reports or other populations。

UGT1A1 gene polymorphism: Impact on toxicity and efficacy of irinotecan-based regimens in metastatic colorectal cancer

AIM: To investigate the correlation between uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) gene polymorphisms and irinotecan-associated side effects and parameters of drug efficacy in patients with metastatic colorectal cancer (mCRC) receiving a low-dose weekly irinotecan chemotherapeutic regimen. METHODS: Genotypes were retrospectively evaluated by gene scan analysis on the ABI 310 sequencer of the TATAA box in the promoter region of the UGT1A1 gene in blood samples from 105 patients who had received 1st line irinotecan-based chemotherapy for mCRC. RESULTS: The distribution of the genotypes was as follows: wild type genotype (WT) (6/6 ) 39.0%, heterozygous genotype (6/7) 49.5%, and homozygous genotype (7/7) 9.5%. The overall response rate (OR) was similar between patients carrying the (6/7, 7/7) or the WT genotype (6/6) (44.3% vs 43.2%, P = 0.75). Neither time to progression [(TTP) 8.1 vs 8.2 mo, P = 0.97] nor overall survival [(OS) 21.2 vs 18.9 mo, P = 0.73] differed significantly in patients who carried the(6/6) when compared to the (6/7, 7/7) genotype. No significant differences in toxicity were observed: Grade 3 and 4 delayed diarrhoea [(6/7, 7/7) vs (6/6); 13.0% vs 6.2%, P =0.08], treatment delays [(6/7, 7/7) vs (6/6); 25.1% vs 19.3%, P = 0.24] or dose reductions [(6/7, 7/7) vs (6/6); 21.5% vs 27.2%, P = 0.07].CONCLUSION: This analysis demonstrates the non-significant influence of the UGT1A1 gene polymorphism on efficacy and rate of irinotecan-associated toxicity in mCRC patients receiving low-dose irinotecan based chemotherapy.

Risk factors and gene polymorphisms of inflammatory bowel disease in population of Zhejiang,China

AIM:To identify the risk factors and three single nucleotide polymorphisms(SNPs) of NOD2/CARD15 gene in inflammatory bowel disease(IBD) of the population in Zhejiang,China.METHODS:A case-control study was conducted using recall questionnaire to collect data on demographic,socioeconomic,lifestyle characteristics and dietary behaviors from 136 determined IBD patients and 136 paired healthy controls.COX regression method was used to screen the statistically significant risk factors for IBD.The polymorphisms of NOD2/CARD15 gene Arg702Trp,Gly908Arg and Leu1007fsinsC were genotyped and further compared between 60 patients with IBD and 60 healthy controls by polymerase chain reaction and restriction fragment length polymorphism.RESULTS:IBD occurred primarily in young and middle-aged people.The mean age for IBD patients was 42.6 years.The ratio of males to females was 1.23:1.COX regression indicated a higher statistical significance in milk,fried food and stress compared with the other postulated risk factors for IBD.None of the patients with IBD and healthy controls had heterozygous or homozygous SNPs variants.CONCLUSION:Milk,fried food and stress are associated with increased risk of IBD.The common variants in NOD2/CARD15 gene are not associated with IBD in China's Zhejiang population.

Plasma Homocysteine and Gene Polymorphisms Associated with the Risk of Hyperlipidemia in Northern Chinese Subjects

Objective To examine the relationship between occurrence of hyperlipidemia, plasma homocysteine and polymorphisms of methylenetetra hydrofolate reductase （MTHFR） gene and methionine synthase （MS） gene. Methods A total of 192 hyperlipidemia patients were selected and divided into hypercholesterolemia group, hypertriglyceridemia group, and combined hyperlipidemia group. Another 208 normal individuals were selected as control. Total plasma homocysteine （tHcy） concentration was measured by high-performance liquid chromatography （HPLC）. Lipid profiles were measured for all subjects The polymorphisms of MTHFR gene C677T and MS gene A2756G were analyzed by PCR-RFLP. Results The tHcy concentration in the combined hyperlipidemia patients was significantly higher than that in the control （15.95μmol/L vs 13.43 μmol/L, P〈0.05）. The prevalence of hyperhomocysteinemia （HHcy） in the combined hyperlipidemia group was significantly higher than that in the control （42.2% vs 23.0%, P=0.015）, with the odds ratio （OR） of 3.339 （95%CI： 1.260-8.849）. The hyperlipidemia patients with HHcy had a higher concentration of total cholesterol （TC） than that in the normal tHcy patients （5.67±0.95 mmol/L vs 5.47±0.92 retool/L, P=0.034）. There was no significant difference in genotype or allele frequencies of MTHFR C677T between the hyperlipidemic and control groups. The hyperlipidemia patients with MTHFR CT/TT genotype had a higher concentration of triglyceride （TG） than those with CC genotype （2.24±1.75 mmol/L vs 1.87±0.95 mmol/L, P〈0.05）. Individuals with CT/TT genotype had a higher concentration of tHcy than those with 677CC genotype both in the hyperlipidemia group （12.61±1.24μmol/L vs 11.20±1.37 μmol/L, P〈0.05） and in the control group （14.04±1.48 μmol/L vs 12.61±1.24 μmol/L, P〈0.05）. The percentage of MS 2756 GG/AG genotype in the combined hyperlipidemia group was significantly higher than that in the control （26.7% vs 13.0%, P=0.012）, with the OR of 3.121 （95%C1： 1.288-7.65/）. The hyperlipidemia patients with MS 2756AG/GG genotype had a higher concentration of TC （5.87±0.89 mmol/L vs 5.46±0.93 retool/L, P〈0.05） and LDL-C （3.29±0.81 mmol/L vs 2.94±0.85 retool/L, P〈0.05） than those with AA genotype. However, individuals with 2756AG/GG genotype showed no significant difference in tHcy among those with AA genotype. Conclusion HHcy and MS A2756G mutation may be the risk factors for combined hyperlipidemia. Further study is needed to confirm the role of HHcy and MS A2756G mutation in the development of hyperlipidemia.

Transforming growth factor-β1 gene polymorphisms are associated with progression of liver fibrosis in Caucasians with chronic hepatitis C infection

AIM: Considerable attention is focused on polymorphisms in the gene encoding transforming growth factor-pi (TGF-β1), a multifunctional cytokine that is in turn a potent growth inhibitor involved in wound healing and differentiation. In humans, it promotes the pathogenesis of organ fibrosis, atherosclerosis, cancer, autoimmune and inflammatory diseases, keloid disease, and hypertrophic scarring. For this reason, much emphasis has been placed on studies elucidating the impact of TGF-β1 and its gene variations for the susceptibility and pathogenesis of these diseases. Unfortunately, some studies have serious limitations. METHODS: We have recently described a high-throughput method for investigation the Arg25Pro polymorphism of human TGF-β1 gene and showed that the frequency of the Pro25 allele is significantly associated with hepatic fibrogenesis. In this report, we describe two novel LightCyder (LC) techniques that facilitate the examination of the two other known alterations in the coding region of TGF-β1. We investigated whether these polymorphisms contribute to hepatitis-induced progression of fibrogenesis in Chinese and Caucasians. RESULTS: In the Chinese ancestry, the gene polymorphisms at codons 25 and 263 were not found and the genetic variant at codon 10 is unlikely to confer susceptibility to hepatic fibrosis. Contrarily, in Caucasians TGF-β1 allelic variations are more frequent and the presence of prolines either in codon 25 or 10 is associated with the interindividual variability in developing more severe fibrosis during chronic hepatitis C infection. CONCLUSION: In summary, these results confirm the hypothesis that TGF-β1 polymorphisms are associated with fibrosis progression in Caucasians chronically infected with hepatitis C.

Mn-SOD and CuZn-SOD polymorphisms and interactions with risk factors in gastric cancer

AIM: To investigate the effects of superoxide dismutase (SOD) polymorphisms (rs4998557 , rs4880), Helicobacter pylori (H. pylori ) infection and environmental factors in gastric cancer (GC) and malignant potential of gastric precancerous lesions (GPL). METHODS: Copper-zinc superoxide dismutase (SOD1, CuZn-SOD)-G7958A (rs4998557 ) and manganese superoxide dismutase (SOD2, Mn-SOD)-Val16Ala (rs4880 ) polymorphisms were genotyped by SNaPshot multiplex polymerase chain reaction (PCR) in 145 patients with GPL (87 cases of gastric ulcer, 33 cases of gastric polyps and 25 cases of atrophic gastritis), 140 patients with GC and 147 healthy controls. H. pylori infection was detected by immunoblotting analysis. RESULTS: The SOD1-7958A allele was associated with a higher risk of gastric cancer [odds ratio (OR) = 3.01, 95% confidence intervals (95% CI): 1.83-4.95]. SOD216Ala/Val genotype was a risk factor for malignant potential of GPL (OR = 2.04, 95% CI: 1.19-3.49). SOD216Ala/genotype increased the risk of gastric cancer (OR = 2.85, 95% CI: 1.66-4.89). SOD1-7958A/genotype, SOD2-16Ala/genotype, alcohol drinking, positive family history and type Ⅰ H. pylori infection were associated with risk of gastric cancer, and there were additive interactions between the two genotypes and the other three risk factors. SOD2-16Ala/Val genotype and positive family history were associated with malignant potential of GPL and jointly contributed to a higher risk for malignant potential of GPL (OR = 7.71, 95% CI: 2.10-28.22). SOD1-7958A/genotype and SOD2-16Ala/genotype jointly contributed to a higher risk for gastric cancer (OR = 6.43, 95% CI: 3.20-12.91). CONCLUSION: SOD1-7958A/and SOD2-16Ala/-genotypes increase the risk of gastric cancer in Chinese Han population. SOD2-16Ala/-genotype is associated with malignant potential of GPL.

Role of matrix metalloproteinase,tissue inhibitor of metalloproteinase and tumor necrosis factor-α single nucleotide gene polymorphisms in inflammatory bowel disease

AIM:To study the (functional) relevance of single nucleotide polymorphisms (SNPs) in genes encoding matrix metalloproteinases (MMP)-1,-2,-3,-9,tissue inhibitors of metalloproteinases (TIMP)-1,-2 and tumor necrosis factor (TNF)-α in the etiopathogenesis of inflammatory bowel diseases (IBD),that may enhance susceptibility and/or disease severity. METHODS:Genomic DNA from 134 Crohn's disease (CD),111 ulcerative colitis (UC) patients and 248 control subjects was isolated from resected intestinal tissue or blood. Allelic composition at SNP loci was determined by PCR-RFLP or tetra primer ARMS PCR. RESULTS:The TIMP-1 genotype TT in women and T in men at SNP +372 T/C was found to increase CD susceptibility (39% vs 23.8%,P=0.018 and 67.9% vs 51.6%,P=0.055,respectively),while women with this genotype were less prone to development of fistulae during follow-up (41.4% vs 68.3%,P=0.025). Male IBD or CD patients carrying the TIMP-1 +372 T-allele expressed lower levels of TIMP-1 in surgically resected macroscopically inflamed tissue (0.065 < P < 0.01). The 5T5T genotype at MMP-3 SNP -1613 5T/6T increased the chance of stenotic complications in CD during follow-up (91.2% vs 71.8%,P = 0.022) but seemed to protect against colonic involvement of this disease at first endoscopic/radiologic examination (35.3% vs 59.5%,P=0.017). CONCLUSION:Allelic composition at the examinedSNPs in genes coding for TIMP-1 and MMP-3 affect CD susceptibility and/or phenotype,i.e.,fistulizing disease,stricture pathogenesis and first disease localisation. These findings reinforce the important role of these proteins in IBD.

Inflammatory cytokine gene polymorphisms increase the risk of atrophic gastritis and intestinal metaplasia

AIM: To investigate the effects of interleukin-8 (IL-8 ), macrophage migration inhibitory factor (MIF ) gene polymorphisms, Helicobacter pylori (H. pylori ) infection, on the risk of developing severe chronic atrophic gastritis (SCAG) and intestinal metaplasia (IM). METHODS: A total of 372 cases were selected from a cohort study in Linqu County, a high risk area for gastric cancer (GC) in northern China. To obtain a sufficient group size, patients with normal or superficial gastritis were included. Based on an average follow-up period of 56 mo, the 372 cases were divided into no progres-sion group (no histological progression from normal or superficial gastritis, n = 137), group Ⅰ (progressed from normal or superficial gastritis to SCAG, n = 134) and group Ⅱ (progressed from normal or superficial gastritis to IM, n = 101). IL-8 , MIF gene polymorphisms were detected by polymerase chain reaction-based denaturing high-performance liquid chromatography analysis and DNA sequencing. RESULTS: An increased risk of SCAG was found in subjects with IL-8-251 AA genotype [odds ratio (OR) = 2.62, 95% CI: 1.23-5.72] or IL-8-251 A allele carriers (AA + AT) (OR = 1.81, 95% CI: 1.06-3.09). An elevated risk of IM was found in subjects with IL-8-251 AT genotype (OR = 2.27, 95% CI: 1.25-4.14) or IL-8-251 A allele carriers (OR = 2.07, 95% CI: 1.16-3.69). An increased risk of SCAG was found in subjects with MIF-173 GC genotype (OR = 2.36, 95% CI: 1.38-4.02) or MIF-173 C allele carriers (GC + CC) (OR = 2.07, 95% CI: 1.21-3.55). An elevated risk of IM was found in subjects with MIF-173 CC genotype (OR = 2.27, 95% CI: 1.16-4.46) or MIF-173 C allele carriers (OR = 3.84, 95% CI: 1.58-9.34). The risk of SCAG and IM was more evident in subjects carrying IL-8-251 A allele (OR = 6.70, 95% CI: 1.29-9.78) or MIF-173 C allele (OR = 6.54, 95% CI: 2.97-14.20) and positive for H. pylori infection. CONCLUSION: IL-8-251 and MIF-173 gene polymorphisms are significantly associated with the risk of SCAG and IM in a population with a high risk of GC in Linqu County, Shandong Province, China.

Relationship between IFN-γ gene polymorphism and susceptibility to intrauterine HBV infection

AIM： To explore the susceptibility of children to intrauterine HBV infection by studying the relationship between IFN-γ gene polymorphism, including IFN-γ＋874A/T single nucleotide polymorphism（SNP） and CA repeat microsatellite polymorphism and intrauterine HBV infection. METHODS： A TaqMan fluorescence polymerase chain reaction in the IFN-γ＋874A/T single nucleotide polymorphism was tested in the intrauterine HBV infection group（group Ⅰ） and the normal immune children group（group Ⅱ）. Capillary electrophoresis was performed in the above two groups to assay the IFN-γ, CA repeat microsatellite polymorphism. RESULTS： Frequencies of AA, AT and TT genotypes were 67.4%, 19.6% and 13.0% in the intrauterine HBV infection group, and 45.2%, 30.1% and 24.7% in the normal immune children group, respectively. A significant difference was found in the frequency distribution of IFN-γ＋874 genotype between the two groups （x^2 = 5.102, P = 0.02389）. In the intrauterine HBV infection group the AA genotype was more common than in the normal immune group. Frequency of IFN-γ＋874A allele was 77.17% in the intrauterine HBV infection group, and 60.27% in the normal immune children group. In the intrauterine HBV infection group the IFN-γ＋874A allele was more common than in normal immune group. A significant difference was found in the frequency distribution between the two groups （x^2= 7.238, P= 0.02389, OR = 2.228, 95% CI = 1.244-3.992）. （CA12）^＋/（CA12）^＋ of IFN-γ CA microsatellite polymorphism was 11.90% in the intrauterine HBV infection group and 26.47% in the normal immune children group. A significant difference was found in the frequency distribution between the two groups （x^2 = 5.64, P = 0.0176）. Frequency of IFN-γ CA repeat was 25% in the intrauterine HBV infection group and 43.38% in the normal immune children group. The frequency of IFN-γ CA repeat was less in the intrauterine HBV infection group than in normal immune group. A significant difference was found in the frequency distribution between the two groups （x^2 = 7.548, P= 0.0060）. CONCLUSION： There is a relationship between IFN-γ＋874A/T SNP and intrauterine HBV infection as well as between IFN-γ CA microsatellite polymorphism and intrauterine HBV infection. IFN-γ gene polymorphism might be important in determining individual＇s susceptibility to intrauterine HBV infection.

Gut bacteria alteration in obese people and its relationshipwith gene polymorphism

AIM:To investigate the differences in cultivable gut bacteria and peroxisome proliferator-activated receptor γ2(PPAR-γ2) gene Pro12Ala variation in obese and normal-weight Chinese people.METHODS:Using culture methods,the amounts of Escherichia coli,Enterococci,Bacteroides,Lactobacilli,Bif idobacteria and Clostridium perfringens(C.perfringens) in the feces of 52 obese participants [body mass index(BMI):≥ 28 kg/m2] and 52 participants of normalweight(BMI:18.5-24 kg/m2) were obtained.Study participants completed comprehensive questionnaires and underwent clinical laboratory tests.The polymerase chain reaction-restriction fragment length polymorphism(PCR-PFLP) assay was used to analyze PPAR-γ2 gene Pro12Ala variation.RESULTS:The obese group exhibited a lower amount of C.perfringens(6.54 ± 0.65 vs 6.94 ± 0.57,P = 0.001)and Bacteroides(9.81 ± 0.58 vs 10.06 ± 0.39,P = 0.012) than their normal-weight counterparts.No major differences were observed in Pro12Ala genotype distribution between the two groups;however,obese individuals with a Pro/Ala genotype had a signif icantly lower level of Bacteroides(9.45 ± 0.62 vs 9.93 ± 0.51,P = 0.027) than those with a Pro/Pro genotype.In addition,the obese group demonstrated a higher stool frequency(U = 975,P < 0.001) and a looser stool(U = 1062,P = 0.015) than the normal-weight group.CONCLUSION:Our results indicated interactions among cultivable gut flora,host genetic factors and obese phenotype and this might be helpful for obesity prevention.

Polymorphisms of alcohol dehydrogenase-2 and aldehyde dehydrogenase-2 and esophageal cancer risk in Southeast Chinese males

AIM： To evaluate the impact of alcohol dehydrogenase-2 （ADH2） and aldehyde dehydrogenase-2 （ALDH2） polymorphisms on esophageal cancer susceptibility in Southeast Chinese males.METHODS： Two hundred and twenty-one esophageal cancer patients and 292 healthy controls from Taixing city in Jiangsu Province were enrolled in this study. ADH2 and ALDH2 genotypes were examined by polymerase chain reaction and denaturing high-performance liquid chromatography. Unconditional logistic regression was used to calculate the odds ratios （OR） and 95% confidence interval （CI）.RESULTS： The ADH G allele carriers were more susceptible to esophageal cancer, but no association was found between ADH2 genotypes and risk of esophageal cancer when disregarding alcohol drinking status. Regardless of ADH2 genotype, ALDH2G/A or A/A carriers had significantly increased risk of developing esophageal cancer, with homozygous individuals showing higher esophageal cancer risk than those who were heterozygous. A significant interaction between ALDH2 and drinking was detected regarding esophageal cancer risk; the OR was 3.05 （95% CI： 2.49-6.25）. Compared with non-drinkers carrying both ALDH2 G/G and ADH2 A/A, drinkers carrying both ALDH2 A allele and ADH2 G allele showed a significantly higher risk of developing esophageal cancer （OR = 8.36, 95% CI： 2.98-23.46）.CONCLUSION： Both ADH2 G allele and ALDH2 A allele significantly increase the risk of esophageal cancer development in Southeast Chinese males. ALDH2 A allele significantly increases the risk of esophageal cancer development especially in alcohol drinkers. Alcohol drinkers carrying both ADH2 G allele and ALDH2 A allele have a higher risk of developing esophageal cancer.