COX-2 polymorphisms -765G →C and -1195A→G and colorectal cancer risk

AIM： TO determine the possible modulating effect of the COX-2 polymorphisms, -765G→C and -1195A→G, on the risk of colorectal cancer （CRC） in a Dutch population. METHODS： This case-control study includes 326 patients with CRC and 369 age- and gender-matched controls. Genotypes of the COX-2 polymorphisms -7dEG→C and -1195A→G were determined by polymerase chain reaction-based restriction fragment length polymorphism. COX-2 genotypes and haplotypes were analyzed and odds ratios with 95% confidence intervals were estimated by logistic regression. RESULTS： The -765GG genotype was associated with an increased risk of developing CRC （OR, 1.45; 95% CI, 1.03-2.04）. No significant difference was observed in the genotype distribution of the -1195A→G polymorphism between patients and controls. The GG/AC haplotype was present significantly less often in patients than in controls （OR 0.44; 95% CI, 0.22-0.85）. When the AC, AG and GG haplotypes were investigated separately, the AC haplotype showed a tendency to be less frequent in patients than in controls （OR（AG/AC） 0.78; 95% CI, 0.57-1.06）. CONCLUSION： The -765GG genotype is associated with an increased risk of developing CRC and the G6/ AC haplotype seems to protect against CRC. These findings suggest a modulating role for the COX-2 polymorphisms -765G→C and -1195A→G in the development of CRC in a Dutch population.     

Single nucleotide polymorphisms of OCTN1, OCTN2, and DLG5 genes in Greek patients with Crohn＇s disease

AIM: To validate novel single nucleotide polymorphisms (SNPs) in Greek patients with Crohn's disease (CD). METHODS: A total of 120 patients with CD, 85 patients with UC, and 100 unrelated healthy controls were genotyped. Genotyping was performed by allele-specific PCR or by PCR-RFLP analysis. RESULTS: Our results showed that the 1672T and -207C alleles were obviously over-represented in CD patients only (P<0.01 and P<0.05, respectively) compared to the control population. The G113A polymorphism was completely absent in our studied population. The odds ratio for the carriage of the TC haplotype was 2.21 for CD patients as compared with controls. Additionally, the frequency of the TC haplotype was increased in patients with ileocolitis or colitis, and was mainly associated with the fibrostenotic phenotype of the disease. Furthermore, when the TC haplotype was compared jointly with the carriage of at least one mutation of the NOD2/CARD15 gene, there was an increased risk for CD, but not for UC, compared to controls. Regarding the location of the disease, the concomitant presence of the TC haplotype and NOD2/CARD15 mutations was mainly associated with ileocolitis or ileitis. CONCLUSION: Collectively, our results suggest that the 1672T variant of the OCTN1 gene and the -207C variant of the OCTN2 gene represent risk factors for CD in the Greek population.     

Effects of angiotensinogen gene polymorphisms on the risk of coronary heart disease in the Chinese population: a meta-analysis

Objective Coronary heart disease （CHD） is a multifactorial disease. This meta-analysis was performed to evaluate the relationship between angiotensinogen gene polymorphisms and CHD in the Chinese population. Methods We searched literature in pubmed （1990- 2010.8） and CNKI （1990-2010.8） for all the relevant studies on 2 angiotensinogen polymorphisms （M235T and T174M） and risk of CHD. The meta-analysis software Stata 10.0 was used for ascertaining heterogeneity among individual studies and for combining all the studies. Furthermore,Egger＇s test and sensitivity analysis were performed to insure authenticity of the outcome.Results Ten associations studies on 2 angiotensinogen polymorphisms （M235T and T174M） were included in this meta-analysis. In a combined analysis, the summary per-allele odds ratio for CHD of the M235T polymorphism was 1.374 （95% confidence interval, 1.019 to 1.852） and T174M polymorphism was 4.089 （95% confidence interval, 1.697 to 9.851）. Conclusions The M235T polymorphism had weak but statistically significant association with CHD while the T174M polymorphism was more strongly associated with a CHD risk in Chinese population, but further confirmation studies are needed     

Comparative analysis of common CFTR polymorphisms poly-T, TG-repeats and M470V in a healthy Chinese population

AIM： To investigate the three important cystic fibrosis transmembrane conductance regulator （CFTR） haplotypes poly-T, TG-repeats and the M470V polymorphisms in the Chinese population, and to compare their distribution with that in Caucasians and other Asian populations. METHODS： Genomic DNA was extracted from blood leukocytes. Exons 9 and 10 of the CFTR gene were obtained through polymerase chain reaction （PCR）. Exon 9 DNA sequences were directly detected by an automated sequencer and poly-T and TG-repeats were identified by direct sequence analysis. Pure exon 10 PCR- amplified products were digested by Hph Ⅰ restriction enzyme and the M470V mutation was detected by the AGE photos of digestion products. RESULTS： T7 was the most common （93.6%） haplotype and the （TG）11 frequency of 57.2% and （TG）12 frequency of 40.9% were dominant haplotypes in the junction of intron 8 （IVS-8） and exon 9. The frequency of T5 was 3.8% and all T5 allele tracts （10 alleles） were joined with （TG）12. Four new alleles of T6 （1.5%） were found in three healthy individuals. In exon 10, the V allele （56.1%） was slightly more frequent than the M allele （43.9%）, and the M/V （45.5%） was the dominant genotype in these individuals. The three major haplotypes T7-（TG）11-V470, T7-（TG）12-M470 and T7-TG11-M470 were related to nearly 86.0% of the population. CONCLUSION： The polymorphisms of poly-T, TG- repeats, and M470V distribution were similar to those in other East Asians, but they had marked differences in frequency from those single haplotype polymorphisms or linkage haplotypes in Caucasians. Thus, they may be able to explain the low incidence of CF and CF-like diseases in Asians.     

IL-10 and TNF-α promoter haplotypes are associated with childhood Crohn＇s disease location

AIM： To determine the distribution and frequencies of the genotypes and haplotypes of the genes encoding for the glucocorticoid receptor （GR）, the tumor necrosis factor （TNF）-α and the interleukin （IL）-10 in childhood Crohn＇s disease （CD） and to assess the impact of the corresponding DNA variants on clinical and disease phenotypes.
METHODS： Ten variants in GR, TNF-a and IL-10 were genotyped in 113 childhood CD cases and 95 healthy subjects, both of French-Canadian origin.
RESULTS： For the GR polymorphisms （R23K and N363S） and IL-10 variants in the 5＇flanking region （-1082 G 〉 A, -819 T 〉 C and -592 A 〉 C）, no difference was observed in allele and genotype frequencies between CD patients and controls. At the haplotype level, we found three IL-10 haplotypes previously described in Caucasians （GCC, ACC and ATA） and three novel haplotypes only present in IBD patients. When we analyzed the haplotype distribution with the anatomical location of the disease, the GCC haplotype was associated with the colonic and the ACC haplotype with the terminal ileum location, respectively. The genotyping of five polymorphisms in the promoter region of the TNF-α gene （-1031 T 〉 C, -863 A 〉 C, -857 T 〉 C, -308 A 〉 G and -238 A 〉 G） revealed a significant overrepresentation of homozygous -1031 CC among CD patients （OR = 9.9） and an association with the colonic location. For TNF-α, eleven haplotypes were inferred, including two frequent ones, TCCGG and CACGG, which were significantly observed more frequently in controls and cases, respectively.
CONCLUSION： This is one of the first studies investigating the association between haplotype structure and disease location in a CD pediatric cohort. Our results will help to increase our understanding of the genetic determinants of childhood CD.     

Prevalence of metabolic syndrome, obesity and diabetes type 2 in cryptogenic cirrhosis

AIM： To evaluate the prevalence of metabolic syndrome （MS）, obesity and type 2 diabetes mellitus （T2DM） in a group of Mexican Mestizo patients with cryptogenic cirrhosis （CC） and to compare this group with patients with cirrhosis secondary to other causes （disease controls）. METHODS： Patients with CC, diagnosed between January, 1990 and April, 2005, were included in a retrospective study. Patients with cirrhosis caused by chronic hepatitis C, alcohol abuse or autoimmune hepatitis （AIH） served as disease controls. RESULTS： A total of 134 patients with CC were analyzed. Disease controls consisted of 81 patients with chronic hepatitis C, 33 with alcohol abuse and 20 with AIH. The median age of patients with CC was 57 years （range, 16-87）; 83 （61.9%） patients were female; 53 （39.6%） were Child A, 65 （48.5%） Child B, and 16 （11.9%） were Child C cirrhosis. The prevalence of MS （29.1% vs 6%; P 〈 0.001）, obesity （16.4% vs 8.2%; P = 0.04） and T2DM （40% vs 22.4%; P = 0.013） was higher in CC patients than in disease controls. There were no differences in sex, age or liver function tests between the two groups. CONCLUSION： The prevalence of MS, obesity and T2DM were higher in patients with CC than in patients with cirrhosis secondary to others causes. Our findings support the hypothesis that non-alcoholic steatohepatitis （NASH） plays an under-recognized role in CC.     

Genetic variations of beta 2-adrenergic receptor gene are associated with essential hypertension in Xinjiang Kazakans

Objective The aims of the present study were to investigate the associations of 46 A〉G, 79 C〉G, 491 C〉T and 659 C〉G genetic variants of the human beta 2-adrenergic receptor （β2-AR）, ADRB2, gene with essential hypertension （EH） in Xinjiang Kazakans population.Methods A gender-matched case-control （271 hypertensive cases and 267 normotensive controls） study was used to investigate the associations of the four variations in the coding region of ADRB2 with EH. The genotypes of the variants were identified by the polymerase chain reaction and restriction fragment length polymorphism （PCR-RFLP） methods. Results 46 A〉G, 79 C〉G and 659 C〉G polymorphisms were common in the Kazakan population, but 491 C〉T was a mutation （frequency ofT allele was only 0.003） and only found in EH group. The fxequency distributions of genotypes and alleles for 659 C〉G between the EH and control groups was significantly different （P〈0.05）, while those for 46 A〉G and 79 C〉G polymorphisms were not statistically different. Logistic regression analysis suggested that the G allele of 659 C〉G polymorphism was a risk factor for hypertension （minor allele vs common homo; odds ratio, 13.240, 95% CI, 4.052-43.274; P〈0.05）. Covariance analysis showed that systolic and diastolic blood pressure levels in GG＋CG group of 659 C〉G were significantly higher than those in the CC group, but no significant difference of blood pressure were found between common homo and minor allele for 46 A〉G and 79C〉G polymorphisms. Haplotype analysis showed that two hyplotypes, HI： 46A-79C-491C-523C（48%）and H5：46A-79C-491C-659G, were associated with EH.Conelusion ADRB2 genetic variants may play independent roles in the molecular genetic mechanism of EH in Xinjiang Kazakans population （d Geriatr Cardio12010; 7：52-57）.     

Increased susceptibility for intrahepatic cholestasis of pregnancy and contraceptive-induced cholestasis in carriers of the 1331T〉C polymorphism in the bile salt export pump

AIM： To study the association of three common ABCB11 and ABCC2 polymorphisms （ABCB11： 1331T〉C→V444A; ABCC2： 3563T〉A → V1188E and 4544G 〉A → C1515Y） with intrahepatic cholestasis of pregnancy （ICP） and contraceptive-induced cholestasis （CIC）. METHODS： ABCB11 and ABCC2 genotyping data were available from four CIC patients and from 42 and 33 ICP patients, respectively. Allele-frequencies of the studied polymorphisms were compared with those in healthy pregnant controls and Caucasian individuals. Furthermore, serum bile acid levels were correlated with the presence or absence of the 1331 C allele. RESULTS： The ABCB11 1331T〉C polymorphism was significantly more frequent in cholestatic patients than in pregnant controls： C allele 76.2% （CI, 58.0-94.4） vs 51.3% （CI 35.8-66.7）, respectively （P = 0.0007）; and CC allele 57.1% （CI 36.0-78.3） vs 20% （CI 7.6-32.4）, respectively （P = 0.0065）. All four CIC patients were homozygous carriers of the C allele. In contrast, none of the studied ABCC2 polymorphism was overrepresented in ICP or CIC patients. Higher serum bile acid levels were found in carriers of the 1331CC genotype compared to carriers of the TT genotype. CONCLUSION： Our data support a role for the ABCB11 1331T〉C polymorphism as a susceptibility factor for the development of estrogen-induced cholestasis, whereas no such association was found for ABCC2. Serum bile acid and 7-glutamyl transferase levels might help to distinguish ABCB4- and ABCB11-related forms of ICP and CIC.     

Promoter polymorphism of transforming growth factor-β1 gene and ulcerative colitis

AIM： To elucidate the possible difference in two promoter polymorphisms of the transforming growth factor-β1 （TGF-β1） gene （-800G 〉 A, -509C 〉 T） between ulcerative colitis （UC） patients and normal subjects.
METHODS： A total of 155 patients with established ulcerative colitis and 139 normal subjects were selected as controls. Two single nucleotide polymorphisms within the promoter region of TGF-β1 gene （-509C 〉 T and -800G 〉 A） were genotyped using PCR-RFLP. RESULTS： There was a statistically significant difference in genotype and allele frequency distributions between UC patients and controls for the -800G 〉 A polymorphism of the TGF-β1 gene （P 〈 0.05）. The frequency of the TGF-β1 gene polymorphism at position -800 showed that the AA genotype and the allele A frequencies significantly differed between the patients and healthy controls （P 〈 0.05）. At position -509, there was no statically significant difference in genotype and allele frequency between the patients and control subjects.
CONCLUSION： The results of our study indicate that there is a significant difference in both allele and genotype frequency at position -800G 〉 A of TGF-β1 gene promoter between Iranian patients with UC and normal subjects.     

Association between calcium sensing receptor gene polymorphisms and chronic pancreatitis in a US population： Role of serine protease inhibitor Kazal 1type and alcohol

AIM： To test the hypothesis that calcium sensing receptor （CASR） polymorphisms are associated with chronic pancreatitis （CP）, and to determine whether serine protease inhibitor Kazal 1type （SPINK1） N34S or alcohol are necessary co-factors in its etiology.
METHODS： Initially, 115 subjects with pancreatitis and 66 controls were evaluated, of whom 57 patients and 21 controls were predetermined to carry the high-risk SPINK1 N34S polymorphism. We sequenced CASR gene exons 2, 3, 4, 5 and 7, areas containing the majority of reported polymorphisms and novel mutations. Based on the initial results, we added 223 patients and 239 controls to analyze three common nonsynonymous single nucleotide polymorphisms （SNPs） in exon 7 （A986S, R990G, and Q1011E）.
RESULTS： The CASR exon 7 R990G polyrnorphism was significantly associated with CP （OR, 2.01; 95% CI, 1.12-3.59; P = 0.015）. The association between CASR R990G and CP was stronger in subjects who reported moderate or heavy alcohol consumption （OR, 3.12; 95% CI, 1.14-9.13; P = 0.018）. There was no association between the various CASR genotypes and SPINK1 N34S in pancreatitis. None of the novel CASR polymorphisms reported from Germany and India was detected.
CONCLUSION： Our United States-based study confirmed an association of CASR and CP and for the first time demonstrated that CASR R990G is a significant risk factor for CP. We also conclude that the risk of CP with CASR R990G is increased in subjects with moderate to heavy alcohol consumption.     

Genotype frequency of gelatinase B C-1562 T polymorphism in coronary heart disease and myocardial infarction

Background One of the characteristics of atherosclerosis is a change in the content of extracellular matrix in thearterial wall.Gelatinase B,a member of the family of matrix metalloproteinase,can regulate extracellular matrixmetabolism and play a role in the pathogenesis of atherosclerosis,coronary heart disease(CHD)and myocardialinfarction(MI).Gelatinase B is polymorphic due to a C to T change at the position-1562 bp in the promoter region.Its relationship with gene product concentration in serum and its role in mediating the risk of CHD and MI in Germansis still unknown.Methods We enrolled 102 controls and 322 patients with angiographically documented CHD,including a sub-group of 173 patients with acute or chronic MI and 80 patients with acute coronary syndrome(ACS).All patients and controls were Germans and genotyped by polymerase chain reaction and digestion with SphI.ResultsWe found that several classical risk factors for CHD and MI,including hypercholesterolemia and cigarette smoking,were significantly increased in CHD and MI patients compared with controls.Serum levels of gelatinase B and tissueinhibitor of metalloproteinase-1 were increased in the peripheral blood of patients with acute coronary syndrome.Nosignificant differences in genotype or allelic frequencies between CHD,MI and control subjects of either men or womenwere found.Our search for a possible association of the polymorphisms with CHD and MI by logistic regression analysiswas also negative.The serum concentrations of gelatinase B showed no differences between genotypes.ConclusionsOur data showed that gelatinase B might provide an index of plaque activity in ACS,but gelatinase B protein was notaffected by genotypes.Also,the T variant of gelatinase B was not associated with CHD or MI in Germans.(J GeriatrCardiol 2004;1(2):114-118.)     

Cyclooxygenase-2 polymorphisms and the risk of esophageal adeno- or squamous cell carcinoma

AIM： TO determine whether -1195 A→G and/or -765 G→C polymorphisms in Cyclooxygenase-2 CCOX-2） may have a risk modifying effect on the development of esophageal carcinoma in a Dutch Caucasian population. METHODS： Two study groups were recruited, 252 patients with esophageal carcinoma and 240 healthy controls, matched for race, age, gender and recruiting area. DNA was isolated from whole blood and used for genotyping. PCR products were digested with restriction enzymes and products were analyzed by agarose gel electrophoresis. Odds ratios （OR） and 95% confidence intervals （CI） were estimated. RESULTS： The distribution of the -1195A→G polymorphism was significantly different in esophageal cancer patients compared to controls. The -1195 GG genotype resulted in a higher risk of developing esophageal adenocarcinoma （OR = 3.85, 95% CI： 1.45-10.3） compared with the -1195AA genotype as a reference. The -765 G→C genotype distribution was not different between the two groups. The GG/ GG haplotype was present more often in esophageal adenocarcinoma patients than in controls （OR = 3.45, 95% CI： 1.24-9.58; with AG/AG as a reference）. The same trends were observed in patients with squamous cell carcinomas, however, the results did not reach statistical significance. CONCLUSION： Presence of the COX-2 -1195 GG genotype and of the GG/GG haplotype may result in a higher risk of developing esophageal carcinoma.     

Association between ALOX5AP gene polymorphisms and coronary artery disease in the Han population of North China

Objectives Recent evidence have implicated specific gene polymorphisms of arachidonate 5-lipoxygenase-activating protein(ALOX5AP),and 2 at-risk haplotypes (HapA,HapB ) in myocardial infarction(MI) and stroke, whereas other studies have been conflicting and to date,no data concerning coronary artery disease(CAD) are available in the Han population of North China.The aim of the present study was to investigate the possible associations between the variants of ALOX5AP gene and susceptibility to CAD in the Han population of North China.Methods We sequenced the promoter,all of the exons,splite site region and 3’untranslated region of ALOX5AP gene,and 7 single nucleotide polymorphisms(SNPs) were found.Three(-1340T/G,+ 8733T/C,+20616G/C) of these polymorphisms were evaluated in 656 patients with angiographically proven CAD and 678 controls with normal coronary angiograms using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) assay.Allelic,genotypic and haplo-typic association testing were performed using Shesis and Phase version 2.1 software package.Multiple logistic regression was used to control for the presence of vascular risk factors.Results While none of the single nucleotide polymorphism (SNP) was found to be associated with CAD risk individually,there was an association with the 3 SNP haplo-types. We identified a protective haplotype -1340T,+8733C and +20616G(Bonferroni-corrected P=0.000002984,OR = 0.623,95%CI=0.519-0.748) and a risk haplotype -1340G, +8733C and +20616G(Bonferroni-corrected P =0.000018, OR=1.728,95%CI=1.375-2.171).The frequencies of all alleles were in Hardy |= Weinberg equilibrium.Conclusions Our data suggest that unique haplotype combinations in the ALOX5AP gene may play a role in the etiology of CAD.     

Association of polymorphisms of interleukin-18 gene promoter region with chronic hepatitis B in Chinese Han population

AIM: To investigate the polymorphisms of interleukin-18 (IL-18) gene promoters, and to disclose whether such polymorphisms are associated with susceptibility to chronic hepatitis B in Chinese Han population. METHODS: Using polymerase chain reaction with sequence specific primers (PCR-SSP) method, the single nucleotide polymorphisms (SNPs) of the promoter region of IL-18 gene at position -607 and -137 were detected in 231 patients with chronic hepatitis B and 300 normal controls. RESULTS: Allele C at position -607 in the promoter of IL-18 gene was detected in 48.7% of normal controls and 51.9% of patients, while allele A at position -607 was detected in 51.3% of normal controls and 48.1% of patients. The frequencies of -607CC, -607 CA and -607AA genotypes in normal controls were 22.0%, 53.3% and 24.7% respectively and in chronic hepatitis B patients were 26.8%, 50.2% and 23.0% respectively. Allele G at position -137 in the promoter of IL-18 gene was detected in 82.3% of normal controls and 88.5% of chronic hepatitis B patients, while allele C at position -137 was detected in 17.7% of normal controls and 11.5% of patients. The frequencies of -137GG, GC and CC genotype were 67.3%, 30.0% and 2.7% in normal controls respectively, while in chronic hepatitis B patients were 78.8%, 19.5% and 1.7% respectively. The frequency of-137GG genotype in chronic hepatitis B groups was significantly higher than that in normal controls (x2=8.55, P=0.003 <0.05), whereas the frequencies of -607C/-137C and -607A/-137C haplotypes in chronic hepatitis B groups were significantly lower than that in normal controls. The association between genotypes of IL-18 promoter region polymorphisms and HBV copies showed that the frequency of -607AA genotype in high HBV-DNA copies groups was lower than that in low HBV-DNA copies groups (x2=6.03, P=0.014 <0.05). CONCLUSION: The polymorphisms of the promoter region of IL-18 gene at position -607 and -137 are closely associated with susceptibility to chronic hepatitis B. The people with allele C at position -137 in the promoter of IL-18 gene may be protected against HBV infection; moreover AA genotype at position -607 may be closely linked to inhibit HBV-DNA replication. These findings give some new clues to the study of pathogenesis of chronic hepatitis B.     

Red blood cell level is increased in obese but not in non-obese patients with coronary heart disease

Objective To examine the changes of red blood cell levels in the obese and non-obese patients with coronary heart disease （CHD） and its clinical significance. Methods 230 cases of coronary heart disease were selected and divided into the obese group and the non- obese group. Obesity and non-obesity were defined based on the body mass index （BMI if 28.0kg/m2）, or waist-hip ratio （men〉 0.9, women〉 0.85）. In addition, 130 healthy subjects were recruited as controls. The pathological status of coronary lesions was quantita- tively analyzed according to the Coronary Vascular Image Segmentation Evaluation Criteria （American Heart Association 1984） and the Gensini scoring system. Results of the changes of both the hemoglobin levels and the red blood cell count in the obese group, the non- obese group with CHD and the control group were compared. Besides, Multivariant Logistic Regression Analysis was applied to assess the correlation between the red blood cells and the coronary artery disease. Results The red blood cell count and the level of hemoglobin in the obese group with CHD was higher than that in the non-obese group with CHD [（4.35 ± 0,55） and （4.13 ± 0.56） 10^9/L; （136.71± 15.87） and （129.96 ±16.23） g/L, P 〈 0.05 in both]; the proportion of acute coronary syndrome in the obese group with CHD was higher in the obese group with CI-/D than that in the non-obese group with CHD （P〈0.05）; Multivariant logistic regression analysis also showed that the red blood cell count was positively correlated with obesity with CHD.Conclusion The red blood cell count and the level of hemoglobin in the obese group were higher than those in the non-obese group; the increase of red blood cell count and hemoglobin level is one of the independent risk factors for the obese patients with CHD.     

Association between hepatocellular carcinoma and type 2 diabetes mellitus in Italy： Potential role of insulin

AIM： To investigate the relationships between Type 2 diabetes mellitus （DM2） and the risk of hepatocellular carcinoma （HCC）.
METHODS： We studied the association between DM2 and HCC in a large case-control study that enrolled 465 consecutive Caucasian patients with HCC （78.3% males, mean age 68.5 ± 8.9 years） compared with an age and sex matched control group of 490 subjects. RESULTS： Prevalence of DM2 was significantly higher in HCC patients （31.2% vs 12.7%; OR = 3.12, 95% CI： 2.22-4.43） and in HCC cases with alcohol abuse. DM2 has been diagnosed before the appearance of HCC in 84.1% of diabetic HCC subjects with mean duration of 141.5 mo, higher in cases treated with insulin than in those with oral antidiabetic agents （171.5 vs 118.7 mo）. Compared to controls, males DM2 with HCC were more frequently treated with insulin （38.1% vs 17.6%, P = 0.009） and with sulfonylurea with or without metformin than with diet with or without metformin （84% vs 68.3%, P = 0.049）. CONCLUSION： DM2 in our patients is associated with a 3-fold increase risk of HCC. In most of our cases DM2 pre-existed to HCC. Patients with DM2 and chronic liver disease, particularly insulin treated males, should be considered for HCC close surveillance programs.     

DNMT3B 579 G〉T promoter polymorphism and risk of esophagus carcinoma in Chinese

AIM：To investigate the relationship between 579 G〉T polymorphisms in the DNMT3B gene, which is involved in de novo methylation and associated with the risk of esophagus cancer （EC） in Chinese. METHODS：DNMT3B 579 G〉T genotypes were determined by PCR-RFLP in 194 EC patients and 210 healthy controls matched for age and sex, who did not receive radiotherapy or chemotherapy for newly diagnosed and histopathologically confirmed EC. RESULTS：In control subjects, the frequency of T/T and G/T genotypes, and T and G alleles was 81.4%, 18.1%, 90.05% and 9.55%, respectively. The distribution of genotypes and allelotypes in the EC patients was not significantly different from that in the controls. When stratified by sex and age, there was still no significant association between the risks of EC and GT and GG genotypes. This study also showed a distinct difference in the distribution of DNMT3B and single nucleotide polymorphism （SNP） between Chinese and Koreans.CONCLUSION：DNMT3B 579 G〉T polymorphism may not be a stratification marker to predict the susceptibility to EC, at least in Chinese. DNMT3B promoter SNP is diverse in ethnic populations.     

Association of genetic variability in glucose-dependent insulinotropic polypeptide receptor and coronary artery disease in Chinese Han type 2 diabetic patients

正Objective To investigate the relationship between glucose-dependent insulinotropic polypeptide receptor(GIPR)gene polymorphisms and the risk of cardiovascular disease in Chinese Han type 2 diabetic patients(T2DM).Methods Of total 666 T2DM patients,390with coronary artery disease(CAD)as cases and 276without CAD as controls were recruited.We selected and     

Clinical significance of NOD2/CARD15 and Toll-like receptor 4 gene single nucleotide polymorphisms in inflammatory bowel disease

AIM： To evaluate the role of genetic factors in the pathogenesis of Crohn＇s disease （CD） and ulcerative colitis （UC）, we investigated the single nucleotide polymorphisms （SNPs） of NOD2/CARD15 （R702W, Gg08R and L1007finsC）, and Toll-like receptor 4 （TLR4） genes （D299G and T399I） in a selected inflammatory bowel disease （IBD） population coming from Southern Italy. METHODS： Allele and genotype frequencies of NOD2/ CARD15 （R702W, Gg08R and L1007finsC） and TLR4 （D299G and T399I） SNPs were examined in 133 CD patients, in 45 UC patients, and in 103 healthy controls. A genotype-phenotype correlation was performed. RESULTS： NOD2/CARD15 R702W mutation was significantly more frequent in CD （9.8%） than in controls （2.4%, P = 0.001） and in UC （2.3%, P = 0.03）. No significant difference was found between UC patients and control group （P 〉 0.05）. In CD and UC patients, no significant association with G908R variant was found. L1007finsC SNP showed an association with CD （9.8%） compared with controls （2.9%, P = 0.002） and UC patients （2.3%, P = 0.01）. Moreover, in CD patients, G908R and L1007finsC mutations were significantly associated with different phenotypes compared to CD wild-type patients. No association of IBD with the TLR4 SNPs was found in either cohort （allele frequencies： D299G-controls 3.9%, CD 3.7%, UC 3.4%, P 〉 0.05; T399I-controls 2.9%, CD 3.0%, UC 3.4%, P 〉 0.05）. CONCLUSION： These findings confirm that, in our IBD patients selected from Southern Italy, the NOD2/ CARD15, but not TLR4 SNPs, are associated with increased risk of CD.     

Replication of interleukin 23 receptor and autophagy-related 16-like 1 association in adult- and pediatric-onset inflammatory bowel disease in Italy

AIM： To investigate gene variants in a large Italian inflammatory bowel disease （IBD） cohort, and to analyze the correlation of sub-phenotypes （including age at diagnosis） and epistatic interaction with other IBD genes. METHODS： Total of 763 patients with Crohn＇s disease （CD, 189 diagnosed at age 〈 19 years）, 843 with ulcerative colitis （UC, 179 diagnosed 〈19 years）, 749 healthy controls, and 546 healthy parents （273 trios） were included in the study. The rs2241880 [autophagy-related 16-like 1 （ATG16L1）], rs11209026 and rs7517847 [interleukin 23 receptor （IL23R）], rs2066844, rs2066845, rs2066847 （CARD15）, rs1050152 （OCTN1）, and rs2631367 （OCTN2） gene variants were genotyped. RESULTS： The frequency of G allele of ATG16L1 SNP （Ala197Thr） was increased in patients with CD compared with controls （59% vs 54% respectively） （OR = 1.25, CI = 1.08-1.45, P = 0.003）, but not in UC （55%）. The frequency of A and G （minor） alleles of Arg381Gln, rs11209026 and rs7517847 variants of IL23R were reduced significantly in CD （4%, OR = 0.62, CI = 0.45-0.87, P = 0.005; 28%, OR = 0.64, CI = 0.55-0.75, P 〈 0.01）, compared with controls （6% and 38%, respectively）. The A allele （but not G） was also reduced signifi cantly in UC （4%, OR = 0.69, CI = 0.5-0.94, P = 0.019）. No association was demonstrated with sub-phenotypes and interaction with CARD15 , and OCTN1/2 genes, although both gene variants were associated with pediatric-onset disease. CONCLUSION： The present study confirms the association of IL23R polymorphisms with IBD, and ATG16L1 with CD, in both adult- and pediatric-onset subsets in our study population.