Genetic polymorphism of MCP-1-2518,IL-8-251 and susceptibility to acute pancreatitis:A pilot study in population of Suzhou,China

AIM： To study the relationship between MCP-1-2518A/ G, IL-8-251A/T polymorphism and acute pancreatitis （AP） in the Han population of Suzhou, China. METHODS： A case-control study was conducted to compare the distribution of genotype and genetic frequency of MCP-1-2518A/G, IL-8-251A/T gene polymorphism among AP （n = 101）, including mild AP （n = 78） and severe AP （n = 23） and control healthy individuals （n = 120） with polymerase chain reaction- restriction fragment length polymorphism （PCR-RFLP） and DNA sequencing, and analyze the relationship between the MCP-1-2518A/G, IL-8-251A/T gene polymorphism and the susceptibility to AP. RESULTS： Significant differences were found in the distribution of genotype of MCP-1-2518A/G between the healthy control group and mild AP group （χ^2 = 32.015, P 〈 0.001）, the same was evident between the healthy control group and severe AP group （χ^2 = 12.932, P 〈 0.05） in Suzhou. However, no difference of genotypic distribution was noted between MAP and SAP （Z2 = 0.006, P = 0.997）. The genetic frequencies of G allele in mild AP were 72.4% （113/156） and 76.1% （35/46） in severe AP, both were higher than the controls, 47.1% （113/240） （χ^2 = 24.804; P 〈 0.001, and 4,2 = 13：005; P 〈 0.001）, but no difference was found between severe AP and mild AP （χ^2 = 0.242, P = 0.623）. No difference was found in the distribution of genotype of IL-8-251A/T between the healthy control group and AP group neither in the frequency of A and T allele. CONCLUSION： The MCP-1-2518 AA genotype of the population in Suzhou may be a protective genotype of AP, while one with higher frequency of G allele is more likely to suffer from pancreatitis. But the genotype of AA and the frequency of G allele could not predict the risk of severe AP. No correlation is found between the IL-8-251 polymorphism and the liability of AP.

Activin A receptor type 1C single nucleotide polymorphisms associated with esophageal squamous cell carcinoma risk in Chinese population

BACKGROUND Transforming growth factor-β(TGF-β)superfamily plays an important role in tumor progression and metastasis.Activin A receptor type 1C(ACVR1C)is a TGF-βtype I receptor that is involved in tumorigenesis through binding to dif-ferent ligands.AIM To evaluate the correlation between single nucleotide polymorphisms(SNPs)of ACVR1C and susceptibility to esophageal squamous cell carcinoma(ESCC)in Chinese Han population.METHODS In this hospital-based cohort study,1043 ESCC patients and 1143 healthy controls were enrolled.Five SNPs(rs4664229,rs4556933,rs77886248,rs77263459,rs6734630)of ACVR1C were assessed by the ligation detection reaction method.Hardy-Weinberg equilibrium test,genetic model analysis,stratified analysis,linkage disequi-librium test,and haplotype analysis were conducted.RESULTS Participants carrying ACVR1C rs4556933 GA mutant had significantly decreased risk of ESCC,and those with rs77886248 TA mutant were related with higher risk,especially in older male smokers.In the haplotype analysis,ACVR1C Trs4664229Ars4556933Trs77886248Crs77263459Ars6734630 increased risk of ESCC,while Trs4664229Grs4556933Trs77886248Crs77263459Ars6734630 was associated with lower susceptibility to ESCC.CONCLUSION ACVR1C rs4556933 and rs77886248 SNPs were associated with the susceptibility to ESCC,which could provide a potential target for early diagnosis and treatment of ESCC in Chinese Han population.

Genetic polymorphisms in glutathione S-transferase T1 affect the surgical outcome of varicocelectomies in infertile patients

Glutathione S-transferases （GSTs）, superoxide dismutase 2 （SOD2） and NAD（P）H：quinone oxidoreductase 1 （NQO1） are anti-oxidant enzyme genes. Polymorphisms of GSTs, SOD2 and NQO1 have been reported to influence individual susceptibility to various diseases. In an earlier study, we obtained preliminary findings that a subset of glutathione S-transferase 7：1 （GSTT1）-wt patients with varicocele may exhibit good response to varicocelectomy. In this study, we extended the earlier study to determine the distribution of genotype of each gene in the infertile population and to evaluate whether polymorphism of these genes affects the results of surgical treatment of varicocele. We analyzed 72 infertile varicocele patients, 202 infertile patients without varicocele and 101 male controls. Genotypes of GSTs were determined by polymerase chain reaction （PCR）. Genotyping of SOD2 and NQO1 was performed using the PCR-restriction fragment length polymorphism （PCR-RFLP） method. A significantly better response to varicocelectomy was found in patients with the GSTTI-wt genotype （63.2%） and NQO1-Ser/Ser genotype （80.0%） than in those with GSTTI-null genotype （35.3%） and NQO1-Pro/Pro or NQO1- Pro/Ser genotype （45.2%）, respectively. The frequencies of glutathione S-transferase M1/T1, SOD2 and NQO1 genotypes did not differ significantly among the varicocele patients, idiopathic infertile patients and male controls. GSTT1 genotype is associated with improvement of semen parameters after varicocelectomy. As the number of patients with NQO1-Ser/Ser genotype was not sufficient to reach definite conclusions, the association of NQO1 genotype with varicocelectomy requires further investigation.

Genetic polymorphisms in cytochrome P4502E1, alcohol and aldehyde dehydrogenases and the risk of esophageal squamous cell carcinoma in Gansu Chinese males

AIM:To evaluate the association between genetic polymorphisms in CYP2E1, ALDH2 and ADH1B and the risk of esophageal squamous cell carcinoma (ESCC) in a high risk area of Gansu Province, in Chinese males. METHODS: A case-control study was conducted to investigate the genetic polymorphisms of these enzymes (CYP2E1 *c1/*c2, ALDH2 *1/*2 and ADH1B *1/*1 genotypes). A total of 80 esophageal cancer cases and 480 controls were recruited. RESULTS: Compared with controls, cases had a greater prevalence of heavier alcohol consumption (53.8% vs 16.2%) and a higher proportion of alcohol drinkers with > 30 drink-years (28.8% vs 13.5%). Heavier alcohol consumption and alcohol drinking with > 30 drink- years increased the risk of ESCC, with ORs (95% CI) of 3.20 (1.32-9.65) and 1.68 (0.96-3.21). CYP2E1 (*c1/*c1), ALDH2 (*1/*2) and ADH1B (*1/*1) genotype frequencies were higher among patients with squamous cell carcinomas, at a level close to statistical significance (P = 0.014; P = 0.094; P = 0.0001 respectively). There were synergistic interactions among alcohol drinking and ALDH2, ADH1B and CYP2E1 genotypes. The risk of the ESCC in moderate-to-heavy drinkers with an inactive ALDH2 encoded by ALDH2 *1/*2 as well as ADH1B encoded by ADH1B *1/*1 and CYP2E1 encoded by CYP2E1 *c1/*c1 was higher than that in the never/rare-to-light drinkers with an active ALDH2 (*1/*1 genotype) as well as ADH1B (*1/*2 + *2/*2) and CYP2E1 (*c1/*c2 + *c2/*c2) genotypes, with a statistically significant difference; ORs (95% CI) of 8.58 (3.28-22.68), 27.12 (8.52-70.19) and 7.64 (2.82-11.31) respectively. The risk of the ESCC in moderate-to-heavy drinkers with ALDH2 (*1/*2) combined the ADH1B (*1/*1) genotype or ALDH2 (*1/*2) combined the CYP2E1 (*c1/*c1) genotype leads to synergistic interactions, higher than drinkers with ALDH2 (*1/*1) + ADH1B (*1/*2 + *2/*2), ALDH2 (*1/*1) + CYP2E1 (*c1/*c2 + *c2/*c2) respectively , ORs (95% CI) of 7.46 (3.28-18.32) and 6.82 (1.44-9.76) respectively. Individuals with the ADH1B combined the CYP2E1 genotype showed no synergistic interaction. CONCLUSION: In our study, we found that alcohol consumption and polymorphisms in the CYP2E1, ADH1B and ALDH2 genes are important risk factors for ESCC, and that there was a synergistic interaction among polymorphisms in the CYP2E1, ALDH2 and ADH1B genes and heavy alcohol drinking, in Chinese males living in Gansu Province, China.

No association between cyclooxygenase-2 and uridine diphosphate glucuronosyltransferase 1A6 genetic polymorphisms and colon cancer risk

AIM：To investigate the association of variations in the cyclooxygenase-2 （COX2） and uridine diphosphate glucuronosyltransferase 1A6 （UGTIA6） genes and non-steroidal anti-inflammatory drugs （NSAIDs） use with risk of colon cancer.METHODS： NSAIDs, which are known to reduce the risk of colon cancer, act directly on COX2 and reduce its activity. Epidemiological studies have associated variations in the COX2 gene with colon cancer risk, but others were unable to replicate this finding. Similarly,enzymes in the UGT1A6 gene have been demonstrated to modify the therapeutic effect of NSAIDs on colon adenomas. Polymorphisms in the UGTIA6 gene have been statistically shown to interact with NSAID intake to influence risk of developing colon adenomas, but not colon cancer. Here we examined the association of tagging single nucleotide polymorphisms （SNPs） in the COX2 and UGTIA6 genes, and their interaction with NSAID consumption, on risk of colon cancer in a population of 422 colon cancer cases and 481 population controls.RESULTS： No SNP in either gene was individually statistically significantly associated with colon cancer, nor did they statistically significantly change the protective effect of NSAID consumption in our sample. Like others, we were unable to replicate the association of variants in the COX2 gene with colon cancer risk （P 〉 0.05）,and we did not observe that these variants modify the protective effect of NSAIDs （P 〉 0.05）. We were able to confirm the lack of association of variants in UGT1A6 with colon cancer risk, although further studies will have to be conducted to confirm the association of these variants with colon adenomas.CONCLUSION： Our study does not support a role of COX2 and UGTIA6 genetic variations in the development of colon cancer.

Cytochrome P450 2E1 genetic polymorphism and gastric cancer in Changle,Fujian Province

AIM: Genetic polymorphism in enzymes of carcinogen metabolism has been found to have the influence on the susceptibility to cancer. Cytochrome P450 2E1 (CYP2E1) is considered to play an important role in the metabolic activation of procarcinogens such as N-nitrosoamines and low molecular weight organic compounds. The purpose of this study is to determine whether CYP450 2E1 polymorphisms are associated with risks of gastric cancer. METHODS: We conducted a population based case-control study in Changle county, Fujian Province, a high-risk region of gastric cancer in China. Ninety-one incident gastric cancer patients and ninety-four healthy controls were included in our study. Datas including demographic characteristics, diet intake, and alcohol and tobacco consumption of individuals in our study were completed by a standardized questionnaire.PCR-RFLP revealed three genotypes:heterozygote (C1/C2) and two homozygotes (C1/C1 and C2/C2) in CYP2E1. RESULTS: The frequency of variant genotypes (C1/C2 and C2/C2) in gastric cancer cases and controls was 36.3% and 24.5%, respectively. The rare homozygous C2/C2 genotype was found in 6 individuals in gastric cancer group(6.6%), whereas there was only one in the control group (1.1%). However, there was no statistically significant difference between the two groups (two-tailed Fisher's exact test P=0.066). Individuals in gastric cancer group were more likely to carry genotype C1/C2 (odds ratio, OR=1.50) and C2/C2 (OR=7.34) than individuals in control group (chi(2) =4.597, for trend P=0.032). The frequencies of genotypes with the C2 allele (C1/C2 and C2/C2 genotypes) were compared with those of genotypes without C2 allele (C1/C1 genotype) among individuals in gastric cancer group and control group according to the pattern of gastric cancer risk factors. The results show that individuals who exposed to these gastric cancer risk factors and carry the C2 allele seemed to have a higher risk of developing gastric cancer. CONCLUSION: Polymorphism of CYP2E1 gene may have some effect in the development of gastric cancer in Changle county, Fujian Province.

Genetic polymorphism of glutathione S-transferase T1 gene and susceptibility to idiopathic azoospermia or oligospermia in northwestern China

Aim： To investigate the association of glutathione S-transferase T1 （GSTT1） gene polymorphism in patients with idiopathic azoospermia or oligospermia in the northwestern China population. Methods： In the case-control study, GSTT1 genotypes were identified by multiplex polymerase chain reaction （PCR） with peripheral blood DNA samples from 78 patients with idiopathic azoospermia, 103 patients with idiopathic oligospermia and 156 age-matched controls with normal sperm concentration and motility, according to the criteria adapted from World Health Organization guidelines. All of the patients and controls were from northwestern China. Results： There is a significant association between GSTT1 null genotype with idiopathic azoospermia risk （odds ratio [OR]： 2.36, 95% confidence interval [CI]： 1.33-4.20, P = 0.003） or idiopathic oligospermia risk （OR： 2.00, 95% CI： 1.17-3.27, P = 0.010）. Conclusion： GSTT1 null genotype is a predisposing risk factor for sporadic idiopathic azoospermia or oligospermia in northwestern China. （Asian J Androl 2008 Mar; 10： 266-270）

GSTM1,GSTT1,GSTP1 and CYP1A1 genetic polymorphisms and susceptibility to esophageal cancer in a French population:Different pattern of squamous cell carcinoma and adenocarcinoma

AIM:To evaluate the association between CYP1A1 and GSTs genetic polymorphisms and susceptibility to esophageal squamous cell carcinoma(SCC)and esophageal adenocarcinoma(ADC)in a high risk area of northwest of France. METHODS:A case-control study was conducted to investigate the genetic polymorphisms of these enzymes (CYPIAI*2C and GSTP1 exon 7 Val alleles,GSTMI*2/*2 and GSTTl *2/*2 null genotypes).A total of 79 esophageal cancer cases and 130 controls were recruited. RESULTS:GSTMI*2/*2 and CYPIAI*IA/*2C genotype frequencies were higher among squamous cell carcinomas at a level dose to statistical significance(OR =1.83,95% CI 0.88-3.83,P=0.11;OR=3.03,95% CI 0.93-9.90,P=0.07, respectively).For GSTP1 polymorphism,no difference was found between controls and cases,whatever their histological status.Lower frequency of GSTT1 deletion was observed in ADC group compared to controls with a statistically significant difference(OR=13.31,95% CI 1.66-106.92,P<0.01). CONCLUSION:In SCC,our results are consistent with the strong association of this kind of tumour with tobacco exposure.In ADC,our results suggest 3 distinct hypotheses: (1)activation of exogenous procarcinogens,such as small halogenated compounds by GSTT1;(2)contribution of GSTT1 to the inflammatory response of esophageal mucosa,which is known to be a strong risk factor for ADC, possibly through leukotriene synthesis;(3)higher sensitivity to the inflammatory process associated with intracellular depletion of glutathione.

GSTT1,GSTM1 and CYP2E1 genetic polymorphisms in gastric cancer and chronic gastritis in a Brazilian population

AIM:To test the hypothesis that,in the Southeastern Brazilian population,the GSTT1,GSTM1 and CYP2E1 polymorphisms and putative risk factors are associated with an increased risk for gastric cancer. METHODS:We conducted a study on 100 cases of gastric cancer (GC),100 cases of chronic gastritis (CG),and 150 controls (C).Deletion of the GSTT1 and GSTM1 genes was assessed by multiplex PCR.CYP2E1/Pst1 genotyping was performed using a PCR-RFLP assay. RESULTS:No relationship between GSTT1/GSTM1 deletion and the c1/c2 genotype of CYP2E1 was observed among the three groups.However,a significant difference between CG and C was observed,due to a greater number of GSTT1/GSTM1 positive genotypes in the CG group.The GSTT1 null genotype occurred more frequently in Negroid subjects,and the GSTM1 null genotype in Caucasians,while the GSTM1 positive genotype was observed mainly in individuals with chronic gastritis infected with H pylori. CONCLUSION:Our findings indicate that there is no obvious relationship between the GSTT1,GSTM1 and CYP2E1 polymorphisms and gastric cancer.

Expression of multidrug resistance 1 gene and C3435T genetic polymorphism in peripheral blood of patients with intractable epilepsy

BACKGROUND： Increased expression of multidrug resistance 1 （MDR1） mRNA in peripheral blood of patients with intractable epilepsy is not due to epilepsy drugs, but epilepsy behavior. Monitoring MDR1 expression in peripheral blood is a target for MDR1 gene evaluation. OBJECTIVE： To investigate the influence of antiepileptic drugs and seizures on MDR expression in intractable epilepsy, and to analyze the genetic polymorphisms of C3435T in the MDRl gene. DESIGN, TIME AND SETTING： Factorial designs and comparative observations at the experimental center of the Affiliated Hospital of Qingdao Medical College, Qingdao University between October 2003 and October 2004. PARTICIPANTS： A total of 120 subjects were recruited from the epilepsy clinical department of the Affiliated Hospital of Qingdao Medical College. Four groups （n = 30） were classified according to statistical factorial design： intractable epilepsy, treatment response, no treatment, and normal control groups. METHODS： One-step semi-quantitative reverse-transcription polymerase chain reaction technology was used to test expressions of the MDR1 gene in 120 subjects. C3435T polymorphisms in intractable epilepsy group and normal control groups were analyzed by polymerase chain reaction-restriction fragment length polymorphism. MAIN OUTCOME MEASURES： Expression of MDR1 mRNA in the four groups, and C3435T genetic polymorphisms in intractable epilepsy and normal control groups. RESULTS： MDRl gene expression was increased in the intractable epilepsy group, due to the factor seizures, but not the antiepileptic drugs. However, the interaction between the two factors was not statistically significant. Of the 30 subjects in the intractable epilepsy group, the following genotypes were exhibited： 3 （10%） C/C genotype, 9 （30%） C/T genotype, and 18 （60%） T/T genotype at the site of C3435T, while 4 （13%）, 10 （33%）, and 16 （53%） subjects were determined to express these genotypes in the normal control group, respectively. C and T allele frequency were 25% and 75% in the intractable epilepsy group, and 30% and 70% in the normal control group, respectively. However, there was no statistical difference between the groups. CONCLUSION： Results demonstrated that seizures, not antiepileptic drugs, induced MDR1 gene expression in intractable epilepsy. Genetic polymorphisms of C3435T in the MDR1 gene did not contribute to the development of multidrug resistance in patients with intractable epilepsy.

Genetic association of rs7754840 and rs7756992 polymorphisms in the CDKAL1 gene and gestational diabetes mellitus in selected Filipino pregnant women

Objective:To investigate the possible association between rs7754840 and rs7756992 polymorphisms of CDKAL1 gene and susceptibility to gestational diabetes mellitus(GDM)in a Filipino pregnant population.Methods:A total of 101 patients with GDM and 99 women without GDM were included.Two CDKAL1 gene single nucleotide polymorphisms(SNPs),namely rs7754840 and rs7756992,were genotyped by using TaqMan allelic discrimination assays.Mann-Whitney U test,median and interquartile range were used to describe physical and biochemical characteristics.The differences in the genotype and allele distribution of the target genetic variants among the two groups of participants were assessed by using Chi-square test.Conformity to Hardy-Weinberg equilibrium was tested prior to conducting further analysis.Multiple logistic regression model was used to investigate the effects of the genotype models on GDM development.Results:There was no observed correlation between the genotypes of the rs7754840 SNP and oral glucose tolerance test parameters.Consequently,there was no significant association between genetic models of the rs7754840 SNP and GDM risk(additive OR 1.43,95%CI 0.82-2.50,P=0.21;dominant OR 1.21,95%CI 0.57-2.59,P=0.62;recessive OR 1.63,95%CI 0.86-3.09,P=0.13).Conclusions:The results of this study suggest no association between CDKAL1 gene variant rs7754840 and GDM development in Filipino pregnant women.Further studies with a larger population should be performed to validate our findings.

Genetic Polymorphisms in ADH1B and ALDH2 Are Associated with Colorectal Tumors in Japan: A Case-Control Study

Background: Unlike with esophageal cancer, acetaldehyde levels and genetic polymorphisms in alcohol dehydrogenase have not yet been shown to be contributing factors for colorectal cancer (CRC). This study aimed to clarify the mechanism of CRC development related to alcohol consumption and to the presence of genetic polymorphisms in the alcohol dehydrogenase, ADH1B and aldehyde dehydrogenase, ALDH2. Methods: This was a case-control study (221 cases and 179 controls) in patients with adenomas and intramucosal tumors who underwent endoscopic removal of all tumors. The amount of alcohol consumption was determined using a self-recorded questionnaire, and the tumor information was obtained from colonoscopy results. Blood samples were taken to analyze the following polymorphisms: ALDH2 Glu504Lys and ADH1B His48Arg. Results: The polymorphisms in ADH1B and ALDH2 had little influence on the development of colorectal adenoma or intramucosal cancer. Patients with ALDH2 (Glu/Glu) were more tolerant of alcohol than those with ALDH2 (Glu/Lys and Lys/Lys). Next, we examined certain combinations of the ADH1B genotypes. In the ALDH2 (Glu/Glu) group, an increased risk (OR = 3.4;95% CI 1.4 - 8.4;P = 0.009) was observed among moderate/heavy drinkers with ADH1B (His/His). In the ALDH2 (Glu/Lys and Lys/Lys) group, an increased risk (OR = 4.2;95% CI 1.1 - 16.7;P = 0.041) was found among moderate/heavy drinkers with ADH1B (Arg/His and Arg/Arg). Conclusions: ADH1B and ALDH2 activity may be involved in the development of CRC.

Association of Genetic Polymorphism of GSTM1 and GSTT1 with the Susceptibility to Antituberculosis Drug-induced Hepatotoxicity in Chinese Population

Objective To investigate the relationship between the polymorphism of glutathione S transferase M1, T1(GSTM1, GSTT1) gene and the susceptibility to antituberculosis drug induced hepatotoxicity (ATDH) in patients with tuberculosis. Methods GSTM1 and GSTT1 gene polymorphisms in patients with or without liver toxicity after antituberculous treatment were analyzed using multiple PCR method. Results In ATDH group and control group, the proportion of GSTM1 gene deletion was 58.0% and 50.7% respectively, and the difference was not statistically significant (OR=1.322, 95%CI=0.921~1.878), the frequencies of GSTT1 deletion were 46.3% and 49.3%, respectively, and there was no significant difference between them. There was no significant difference in frequency of GSTM1 and GSTT1 variation between case group and control group (P> 0.05), and no synergistic effect of those two gene polymorphism were detected in the occurrence of antituberculosis drug-induced hepatotoxicity. Conclusion The polymorphisms of GSTM1 and GSTT1 genes may not be associated with the risk of ATDH.

Influence of organic anion transporting potypeptide(SLCO1B1 and SLCO1B3)genetic polymorphisms on mycophenolic acid in Chinese kidney transplantation patients

Objective To analyze the relationship between genetic polymorphisms of organic anion transporting polypeptide ( SLCO1B1 and SLCO1B3) and mycophenolic acid ( MPA) pharmacokinetics in Chinese kidney transplant recipients. Methods Gene mutations ( SLCO1B3 T334G,SLCO1B1 A338G) were detected in 68 recipi-

Correlation between IL-1β,IL-1Ra gene polymorphism and occurrence of polycystic ovary syndrome infertility

Objective:To explore the relationship between IL-1β.IL-1Ra gene polymorphism and the occurrence of polycystic ovary syndrome(PCOS) infertility.Methods:A total of 59 PCOS infertility cases visiling the reproductive center of our hospital from Mar.2010 to Mar.2012 and 56 healthy women were selected.ELISA method was used lor the detection of IL-1β.IL-1Ra lewis,and the levels of serum supersensitivity C reaction protein(US-CRP).insulin(FINS),follieule-stimulating hormone(FSH) and fasting blood—glucose(FRG) were detected.PCR analysis technology was adopted to detect the gene polymorphism of the.511 site of IL-1βand the second introne of IL- 1Ra.Results:The levels of IL-1β.IL-1Ra.US-CRP.FINS and FBG in blood scrum of patients in PCOS group were significantly higher than those in control group(P【0.05 or P【0.01).The level of FSH in PCOS group was significantly lower than that in control group(P【0.05).The genotypic frequency of T/T.the 511 site of IL-1βin PCOS group was 42.37%.significantly higher than 1250%in control group 【P【0.01).The frequency of T allele was also significantly higher than that in control group(P【0.01).The genotypic frequency ofⅠ/Ⅴ.the second introne of IL-1Ra in PCOS group was 20.34%,signicianlly higher than 3.57%in control group(P【0.05).The frequency of V allele in PCOS group was significantly higher than that in control group(P【0.05).Conclusions: T allele of the 511 site of IL-1βgene and V allele of the second inlrone of IL-1Ra gene might be the genetic basis of the rising of IL-1β.IL-1Ra and US-CRP levels in blood serum of PCOS patients,and are associated with the infertility occurrence of PCOS patients.

Association of IL-17 polymorphisms with gastric cancer risk in Asian populations

AIM: To investigate associations between the IL-17 rs2275913 G>A and rs763780 T>C polymorphisms and susceptibility to gastric cancer in Asian populations. METHODS: We reviewed studies published up to 2014 on IL-17 polymorphisms with gastric cancer susceptibility systematically. Relevant articles were identified in the MEDLINE, Science Citation Index, Cochrane Library, Pub Med, EMBASE, CINAHL and Current Contents Index databases. We used version 12.0 STATA statistical software to evaluate the statistical data. Two reviewers abstracted the data independently. Odds ratios(ORs) and 95% confidence intervals(95%CIs) were calculated. RESULTS: Seven independent, case-control studies were chosen for the meta-analysis, which included 3210 gastric cancer patients and 3889 healthy controls. The overall estimation showed a positive association between the IL-17 rs2275913 G>A polymorphism and the occurrence of gastric cancer for five genetic models(all P < 0.05) and similar results were observed for the IL-17 rs763780 T>C variation with four genetic models(all P < 0.05), but not for the dominant model(P > 0.05). Subgroup analysis by country revealed that the rs2275913 G>A and rs763780 T>C polymorphisms may be the main risk factor for gastric cancer in Chinese and Japanese populations. CONCLUSION: The IL-17 gene may be significantly correlated with gastric cancer risk in Asian populations, especially those carrying the rs2275913 G>A and rs763780 T>C polymorphisms.

TNF-α and IL-1RA Polymorphisms and Silicosis Susceptibility in Chinese Workers Exposed to Silica Particles:A Case-Control Study

Abstract Objective To assess the association of TNF-α and IL-1RA SNPs with the risk of silicosis in Chinese workers exposed to silica particles. Methods Case-control study design was used to enroll 68 silicotic patients induced by silica particles and 68 healthy workers matched for length of silica particle exposure as controls. Both cases and controls were from the same company in southwest China, and each of them was requested to complete a questionnaire. Blood samples were drawn for genomic DNA extraction from each participant. The genotyping of TNF-α （-238 and -308） and IL-1RA （＋2018） was performed using polymerase chain reaction-based restriction fragment length polymorphism （PCR-RFLP） and SYBR green-based quantitative polymerase chain reaction {qPCR）, respectively. Unconditional logistic regression model was used to estimate odds ratios （ORs） and their 95% confidential intervals （Cl） for SNPs. Results No significant differences were found between cases and controls in particles exposure length, body mass index （BMI）, and status of smoking and alcohol consumption except for age （P=O.O01） and blood type （P=0.042）. The frequencies of TNF-c（（-238） and IL-1RA （＋2018） genotypes in cases were significantly different from those in controls, （P=O.O01 and P=0.O02, respectively）, while a borderline significant difference was found in the frequencies of TNF-α（-308） between cases and controls （P=0.063）. The variants of three SNPs increased the risk of silicosis in the Chinese workers exposed to silica particles. The adjusted ORs of TNFα（-308）, TNF-α（-238） and IL-1RA （＋2018） were 2.8 （95% Ch 2.1-7.5）, 20.9 （95% Ch 2.8-236.4） and 4.0 （95% CI： 2.6-10.2）, respectively. Conclusion It is suggested that cytokine polymorphisms of TNF-ct （-238, -308） and IL-1RA （＋2018） are associated with the risk of silicosis in the Chinese workers exposed to silica particles. Further independent studies on the interaction between SNPs and exposure to silica particles with a larger sample size are therefore warranted.

No relationship between IL-1B gene polymorphism and gastric acid secretion in younger healthy volunteers

AIM: To investigate the influence of IL-1B-511 gene polymorphism on IL-1B mRNA expression and gastric acid output in individual with or without Helicobacter pylori (H pylori) infection.METHODS: IL-1B mRNA expression and gastric acid secretion in 117 health volunteers were assayed using semi-quantitative RT-PCR and gastric juice assay, respectively. Pepsinogen (PG) Ⅰ and Ⅱ of 255 subjects (including 117 health volunteers) were also examined.RESULTS: T/T genotype individuals with H pylori infection had a more decreased PG Ⅰ/Ⅱ ratio. In gastric antrum mucosa, the individuals with H pylori infection had higher IL-1B expression than those without H pylori infection, but there was no obvious difference among each genotype. In gastric corpus, the individuals with H pylori infection had a significantly higher IL-1B expression than those without H pylori infection. IL-1B-511T/T genotype was markedly higher as compared with the other two genotypes. Both maximal acid output and basic acid output were similar among each genotype in IL-1B-511 gene locus, regardless of H pylori infection.CONCLUSION: IL-1B-511 T allele does not decrease gastric acid output, although it has a stimulated influence on IL-1B expression. Consequently, the pathway,through which IL-1B plays a central role in gastric cancer development, might not depend on low acid, but on the other regulation mechanisms.

Genetic polymorphisms in HIFIA are associated with prostate cancer risk in a Chinese population

The hypoxia-inducible factor-1α（HIF-1α） plays an important role in regulating angiogenesis, which is essential for tumor growth and metastasis. Genetic variations of HIFIA （coding HIF-1α） have been shown to influence an individual＇s susceptibility to many human tumors; however, evidence on associations between HIFIA single-nucleotide polymorphisms （SNPs） and prostate cancer （PCa） risk is conflicting. We genotyped three potentially functional polymorphisms in HIFIA （rs11549465, rs11549467 and rs2057482） using the TaqMan method and assessed their associations with PCa risk in a case-control study of 662 PCa patients and 716 controls in a Chinese Hart population. Compared with rs 11549467 GG genotype, the variant genotypes GA ＋AA had a significantly increased PCa risk （adjusted odds ratio （OR）= 1.70; 95% confidence interval （C1）= 1.06-2.72）, particularly among older patients （0R=2.01; 95%C1 = 1.05-3.86）, smokers （0R=2.06; 95%C1 = 1.07-3.99）, never drinkers （OR=2.16; 95%C1 = 1.20-3.86） and patients without a family history of cancer （OR= 1.71; 95%C1= 1.02-2.89）. Furthermore, patients with rs11549467 variant genotypes were associated with a higher Gleason score （OR=2.14; 95%CI = 1.22-3.75）. No altered PCa risk was associated with the rs 11549465 and rs2057482 polymorphism. However, the combined variant genotypes of rs2057482 and rs 11549467 were associated with increased PCa risk （0R=2.10; 95%C1= 1.23-3.57 among subjects carrying three or more risk alleles）. These results suggest that HIFIA polymorphisms may impact PCa susceptibility and progression in the Chinese Han population.

Correlation between single nucleotide polymorphism of rs3811047 in IL-1 F7 gene and rheumatoid arthritis susceptibility among Han population in central plains of China

Objective:To discuss the association between single nucleotide polymorphism(SNP) of rs3811047 in IL-1 F7 gene and rheumatoid arthritis(RA) susceptibility among the Han population in central plains of China.Methods:A total of 276 RA patients admitted to our hospital from December 2009 to December 2011 together with 276 healthy physical examinees in the same period were chosen as the subjects.The typing for rs3811047 SNP in IL-1 F7 gene was carried out by using ligase detection reaction and polymerase chain reaction technique.And the frequency of each allele and genotypes distribution was calculated so as to evaluate the association between genotype distribution and RA susceptibility.Results:The frequency of A allele of rs3811047 in IL-1 F7 gene in RA group and control group was 16.27%and 17.68%,respectively,and that of G allele in two groups was 83.73%and 82.32%,respectively.The difference between two groups wasn’t statistical significant(P 】0.05).The frequency of genotype AA,AG and GG in RA group was 2.19%,27.84%and 69.97%,respectively,while that in control group was 2.94%,29.78%and 67.28%, respectively.The difference of distribution of three genotypes was not statistically significant (P 】0.05).RA patients with A allele were better than those without A allele in joint swelling index, rest pain,HAQ scoring and blood sedimentation.There was significant difference between two groups in above indexes(P【0.05/P【0.01).Conclusions:No significant correlation between RA susceptibility among the Han population in central plains of China and rs3811047 SNP inIL-1 F7 gene is observed.However,A allele of rs3811047 has certain influence on the condition of RA patients.