Association between Gene Polymorphisms and SNP-SNP Interactions of the Matrix Metalloproteinase 2 Signaling Pathway and the Risk of Vascular Senescence

Objective This study aimed to explore the association of single nucleotide polymorphisms(SNP)in the matrix metalloproteinase 2(MMP-2)signaling pathway and the risk of vascular senescence(VS).Methods In this cross-sectional study,between May and November 2022,peripheral venous blood of151 VS patients(case group)and 233 volunteers(control group)were collected.Fourteen SNPs were identified in five genes encoding the components of the MMP-2 signaling pathway,assessed through carotid-femoral pulse wave velocity(cf PWV),and analyzed using multivariate logistic regression.The multigene influence on the risk of VS was assessed using multifactor dimensionality reduction(MDR)and generalized multifactor dimensionality regression(GMDR)modeling.Results Within the multivariate logistic regression models,four SNPs were screened to have significant associations with VS:chemokine(C-C motif)ligand 2(CCL2)rs4586,MMP2 rs14070,MMP2rs7201,and MMP2 rs1053605.Carriers of the T/C genotype of MMP2 rs14070 had a 2.17-fold increased risk of developing VS compared with those of the C/C genotype,and those of the T/T genotype had a19.375-fold increased risk.CCL2 rs4586 and MMP-2 rs14070 exhibited the most significant interactions.Conclusion CCL2 rs4586,MMP-2 rs14070,MMP-2 rs7201,and MMP-2 rs1053605 polymorphisms were significantly associated with the risk of VS.

Quantitative assessment of the relevance of organic-aniontransporting-polypeptide 1B1 and 2B1 polymorphisms in fexofenadine pharmacokinetic variants via pharmacometrics

Fexofenadine is useful in various allergic disease treatment.However,the pharmacokinetic variability information and quantitative factor identification of fexofenadine are very lacking.This study aimed to verify the validity of previously proposed genetic factors through fexofenadine population pharmacokinetic modeling and to explore the quantitative correlations affecting the pharmacokinetic variability.Polymorphisms of the organic-anion-transporting-polypeptide(OATP)1B1 and 2B1 have been proposed to be closely related to fexofenadine pharmacokinetic diversity.Therefore,modeling was performed using fexofenadine oral exposure data according to the OATP1B1-and 2B1-polymorphisms.OATP1B1 and 2B1 were identified as effective covariates of clearance(CL/F)and distribution volume(V/F)-CL/F,respectively,in fexofenadine pharmacokinetic variability.CL/F and average steady-state plasma concentration of fexofenadine differed by up to 2.17-and 2.20-folds,respectively,depending on the OATP1B1 polymorphism.Among the individuals with different OATP2B1 polymorphisms,the CL/F and V/F differed by up to 1.73-and 2.00-folds,respectively.Ratio of the areas under the curves following single-and multiple-administrations,and the cumulative ratio were significantly different between OATP1B1-and 2B1-polymorphism groups.Based on quantitative prediction comparison through a model-based approach,OATP1B1 was confirmed to be relatively more important than 2B1 regarding the degree of effect on fexofenadine pharmacokinetic variability.Based on the established pharmacokineticpharmacodynamic relationship,the difference in fexofenadine efficacy according to genetic polymorphisms of OATP1B1 and 2B1 was 1.25-and 0.87-times,respectively,and genetic consideration of OATP1B1 was expected to be important in the pharmacodynamics area as well.This population pharmacometrics study will be a very useful starting point for fexofenadine precision medicine.

基于MS(2)-AR-TVTP模型的I_(BD)波动周期非对称性和持续性分析

国际干散货运输市场源于国际贸易的衍生需求,受世界经济的影响,是一个典型的周期性市场。选取1999年11月~2021年12月的波罗的海干散货运价指数(I_(BD))月度数据,在检验序列平稳性的基础上,确定最优滞后长度,构建两区制的时变转换概率马尔科夫转换自回归模型,分析I_(BD)波动周期的持续时间、转换拐点和非对称性等主要特征。研究结果表明:模型能有效拟合I_(BD)波动周期的主要特征,周期平均持续时间为33.7个月,自2008年9月之后呈缩短态势,上升期和下降期交互更频繁;I_(BD)波动周期具有非对称性,周期内上升期持续时间比下降期长,I_(BD)维持上升期更具有稳定性。周期性特征结果可为干散货航运业造船投资和市场经营提供决策依据。

O_(2)/Ar预热处理和K原子对预热焦炭燃烧机理的影响机制

煤粉预热燃烧技术和催化燃烧技术可在保证预热焦炭高燃烧效率的同时降低温室气体及氮氧化物的排放。采用原子偶极矩校正的Hirshfeld(ADCH)和静电势(ESP)方法深入揭示O_(2)/Ar预热处理和K原子对预热焦炭(SC-Ar和SC-K-O_(2)Ar)结构特性的影响,并通过密度泛函理论(DFT)探究SC-Ar和SC-K-O_(2)Ar的燃烧机理。结果表明,焦炭内K和酚官能团的存在有效改变了SC-Ar和SC-K-O_(2)Ar的ADCH和ESP特性,其中,C_(6)、C_(7)、C_(8)和C_(9)的ADCH电荷分别由0.18e、0.03e、−0.25e和−0.01e变为−0.41e、0.01e、0.11e和−0.16e。在ADCH有色图中,由于O原子和K原子对电子的吸附能力显著强于C原子,所以,羟基中的H原子和K原子的正电荷特性更显著。K原子的ADCH电荷为0.68e,—OH中的H原子的ADCH电荷为0.34e。由所构建的焦炭燃烧路径可知,SC-K-O_(2)Ar和SC-Ar的燃烧本质为焦炭内芳香环的断裂及重组。在SC-K-O_(2)Ar的燃烧过程中,主要存在2条反应路径(Path 1和Path 2)。其中Path 1的决速步为■,能垒为325.01 kJ/mol,略低于Path 2中决速步(■)的能垒(360.98 kJ/mol),说明SC-K-O_(2)Ar的燃烧主要遵循反应路径Path 1。SC-Ar的燃烧路径亦有2条(Path 3和Path 4),Path 3的决速步为■,能垒为430.34 kJ/mol,Path 4的决速步为■能垒为425.09 kJ/mol,略低于Path 3的决速步能垒,说明SC-Ar的燃烧主要遵循路径Path 4。Path 4的决速步能垒低于Path 1,因此,SC-KO_(2)Ar的燃烧比SC-Ar更易发生,说明O_(2)/Ar预热处理和K原子可有效促进预热焦炭的燃烧。

感性耦合Ar/O_(2)等离子体放电特性的数值模拟

本文采用流体力学模型对不同腔室材质下的感性耦合Ar/O_(2)等离子体放电特性进行研究.结果表明,由于中性粒子在不同材质表面的黏附系数不同,因而腔室材质对各活性粒子的密度和空间分布产生了显著的影响.依次采用不锈钢、阳极Al_(2)O_(3)和Cu腔室进行放电,发现电子、O^(+)、Ar^(+)、O、O(1D)和Ar_(m)的密度逐渐增大,O_(2)^(+),O^(-),O_(2)和O_(2)(a^(1)Δg)的密度变化趋势相反,各粒子的空间分布特点也有明显差异.在不同腔室中,电子在腔室中心区域的分布是均匀的;O和O_(2)(a^(1)Δg)的密度最大值位于腔室中心,并沿径向逐渐降低;而Ar^(+)和Ar_(m)的密度峰值出现在线圈下方;O^(+),O_(2)^(+)和O(^(1)D)的密度最大值却随着腔室的变化从线圈下方逐渐向腔室中心方向移动;C-离子则被局域在线圈和极板之间一个非常小的区域.最后,讨论了表面反应O→1/2O_(2)的黏附系数对O和O_(2)的影响,发现随着黏附系数的增大,O密度逐渐降低,O_(2)密度变化趋势相反,而且当黏附系数增大到0.5以上时,二者的密度几乎不再受黏附系数的影响.

The influence of β_2AR polymorphisms as a predictor of successful short acting β_2-agonist nebulization during asthmatic exacerbation

Aim:In this study,we would like to determine associations between β2-Adrenergic Receptor(β2AR)polymorphisms at codon 16 and 27 and the response to short acting β2-agonist during asthmatic exacerbation.Methods:This was a prospective cross-sectional study of one year duration.One hundred and thirty two asthmatic patients were recruited.Five mls of venous blood was taken for DNA extraction and then genotyped for the β2AR polymorphisms using multiplex PCR.Patient's clinical responses to β2-agonist nebulization were then compared to their genotype to determine the association.Results:We found that there was no association between β2AR polymorphisms at both codon 16 and 27 with response towards short acting β2-agonist,P=0.315 and P=0.706 respectively.Conclusion:We suggested that β2AR polymorphisms at both codon 16 and 27 had no influent on the response to short acting β2-agonist.

KCNQ1 rs2237895 gene polymorphism increases susceptibility to type 2 diabetes mellitus in Asian populations

BACKGROUND The association of single nucleotide polymorphism of KCNQ1 gene rs2237895 with type 2 diabetes mellitus(T2DM)is currently controversial.It is unknown whether this association can be gene realized across different populations.AIM To determine the association of KCNQ1 rs2237895 with T2DM and provide reliable evidence for genetic susceptibility to T2DM.METHODS We searched PubMed,Embase,Web of Science,Cochrane Library,Medline,Baidu Academic,China National Knowledge Infrastructure,China Biomedical Literature Database,and Wanfang to investigate the association between KCNQ1 gene rs2237895 and the risk of T2DM up to January 12,2022.Review Manager 5.4 was used to analyze the association of the KCNQ1 gene rs2237895 polymorphism with T2DM and to evaluate the publication bias of the selected literature.RESULTS Twelve case–control studies(including 11273 cases and 11654 controls)met our inclusion criteria.In the full population,allelic model[odds ratio(OR):1.19;95%confidence interval(95%CI):1.09–1.29;P<0.0001],recessive model(OR:1.20;95%CI:1.11–1.29;P<0.0001),dominant model(OR:1.27.95%CI:1.14–1.42;P<0.0001),and codominant model(OR:1.36;95%CI:1.15–1.60;P=0.0003)(OR:1.22;95%CI:1.10–1.36;P=0.0002)indicated that the KCNQ1 gene rs2237895 polymorphism was significantly correlated with susceptibility to T2DM.In stratified analysis,this association was confirmed in Asian populations:allelic model(OR:1.25;95%CI:1.13–1.37;P<0.0001),recessive model(OR:1.29;95%CI:1.11–1.49;P=0.0007),dominant model(OR:1.35;95%CI:1.20–1.52;P<0.0001),codominant model(OR:1.49;95%CI:1.22–1.81;P<0.0001)(OR:1.26;95%CI:1.16–1.36;P<0.0001).In non-Asian populations,this association was not significant:Allelic model(OR:1.06,95%CI:0.98–1.14;P=0.12),recessive model(OR:1.04;95%CI:0.75–1.42;P=0.83),dominant model(OR:1.06;95%CI:0.98–1.15;P=0.15),codominant model(OR:1.08;95%CI:0.82–1.42;P=0.60.OR:1.15;95%CI:0.95–1.39;P=0.14).CONCLUSION KCNQ1 gene rs2237895 was significantly associated with susceptibility to T2DM in an Asian population.Carriers of the C allele had a higher risk of T2DM.This association was not significant in non-Asian populations.

Relationship between the rs2241766 ADIPOQ Polymorphism in a Black African Population and the Occurrence of Type 2 Diabetes

Background: Type 2 diabetes mellitus (T2DM) is a metabolic disease, characterized by chronic hyperglycemia. This pathology is linked to various genes whose interaction with the environment promotes its development. The aim of this work was to determine the relationship between the rs2241766 (T/G) polymorphism of the ADIPOQ gene with type 2 diabetes in the black population. Material and Methods: This work was a case-control study, involving type 2 diabetics subjects (n = 94) and controls (n = 82). The study took place from September 2022 to September 2023. Patients were recruited in the Endocrinology Department of the Libreville University Hospital Center. Analysis was performed in the Biochemistry laboratory of the University of Health Sciences in Libreville and at the Research Institute of Health Sciences of Bobodioulasso. Genomic DNA was extracted using the protocol Qiagen kit and the PCR-RFLP method was used to determine the rs2241766 (T/G) polymorphism of the ADIPOQ gene. Results: Only 2 genotypes were found in this population, the TT genotype and the GT genotype. The proportions were not different between the two groups (p = 0.1095) neither the distribution of G and T alleles (p = 0.1095). On the other hand, the HDL hypocholesterolemia was frequent in subjects with the GT genotype compared to TT heterozygous (51.1% vs 48.9%, p = 0.0280;OR = 0.55 [0.30 - 1.01]). Conclusion: There was no association between the rs2241766 (T/G) variant of the ADIPOQ gene and the occurrence of type 2 diabetes in this population. On the other hand, a relationship between HDL hypocholesterolemia and the GT genotype has been established.

Toll-like receptors 2 polymorphism is associated with psoriasis: A case-control study in the northern Chinese population

Background:Psoriasis is a disease caused by genetics and immune system dysfunction,affecting the skin and joints.Toll-like receptors(TLRs)play an important role in triggering the innate immune response and controlling adaptive immunity.The role of TLR2 in the progression of psoriasis is not well understood.Methods:A case-control study was conducted on a northern Chinese Han population,consisting of psoriasis patients and healthy control subjects.Genotyping was performed using the tetra-primer amplification refractory mutation system-polymerase chain reaction(ARMS-PCR),and allele and genotype frequencies of four SNPs in TLR2 were analyzed in 270 psoriasis patients and 246 healthy controls.Results:Four TLR2 SNPs(rs11938228,rs4696480,rs3804099,rs5743699)were genotyped and found to be in linkage disequilibrium.The genotype distributions of rs11938228 and rs4696480 in two groups were in Hardy-Weinberg equilibrium and statistically significant except for the overdominance model.The haplotypes ATTC and ATCC were found to be protective against psoriasis.Conclusion:Our study found a correlation between TLR2 genetic variations and the likelihood of psoriasis in northern China.

Discharge mode and particle transport in radio frequency capacitively coupled Ar/O_(2) plasma discharges

Simulations are conducted on capacitively coupled Ar/O_(2)mixed gas discharges employing a one-dimensional fluid coupled with an electron Monte Carlo(MC)model.The research explores the impact of different O_(2)ratio and pressures on the discharge characteristics of Ar/O_(2)plasma.At a fixed Ar/O_(2)gas ratio,with the increasing pressure,higher ion densities,as well as a slight increase in electron density in the bulk region can be observed.The discharge remains dominated by the drift-ambipolar(DA)mode,and the flux of O(3P)at the electrode increases with the increasing pressure due to higher background gas density,while the fluxes of O(1D)and Ardecrease due to the pronounced loss rate.With the increasing proportion of O_(2),a change in the dominant discharge mode from a mode to DA mode can be detected,and the O_(2)-associated charged particle densities are significantly increased.However,Ar+density shows a trend of increasing and then decreasing,while for neutral fluxes at the electrode,Arflux decreases,and O(3P)flux increases with the reduced Ar gas proportion,while trends in O(1D)flux show slight differences.The evolution of the densities of the charged particle and the neutral fluxes under different discharge parameters are discussed in detail using the ionization characteristics as well as the transport properties.Hopefully,more comprehensive understanding of Ar/O_(2)discharge characteristics in this work will provide a valuable reference for the industry.

2AR技术在初中化学实验中的应用研究

文章概述了2AR技术的基本概念及其在化学实验教学中的适用性,分析了2AR技术在提升实验教学质量及促进学生创新能力方面的价值,讨论了实施过程中可能遇到的问题,并基于以上分析提出了2AR技术在初中实验中的应用策略,以期为初中化学实验教学提供新的视角和方法论,推动实验教学改革。

Roles of the Apolipoprotein E Gene and Its Polymorphisms in the Etiopathophysiology of Type 2 Diabetes Mellitus and Its Atherosclerotic Complication in Senegalese Females

Lipid metabolism disorders would be among the components responsible for the risk of the onset of T2DM and its vascular complications. Apolipoprotein E plays an important role in lipid metabolism. We studied the involvement of the APOE gene in the onset of T2DM and its vascular complications. Clinical and biochemical parameters were assessed in each participant. APOE genotypes were identified by PCR-RFLP. Arterial stiffness was studied using a pOpmetre® which evaluates the pulse wave velocity (ft-PWV). Endothelial dysfunction was studied using an EndoPAT2000® which measures endothelium-dependent vasodilation (RHI). In control subjects, the ε3 allele was associated with an increase in fasting blood glucose (r = 2.36, p = 0.018), and a decrease in LDL cholesterol levels (r = −2.17, p = 0.03), and ε4 was associated with an increase in total cholesterol (r = 2.59, p = 0.01), LDL cholesterol (r = 2.84, p = 0.004), and No-HDL cholesterol (r = 2.74, p = 0.006). In type 2 diabetes subjects, the ε2 was associated with a decrease in diastolic blood pressure (r = −2.25, p = 0.02). The ε3 was associated with a decrease in ft-PWV (r = −2.26, p = 0.024) while the ε4 was associated with an increase in ft-PWV (r = 2.52, p = 0.012). Carrying the ε2ε3 genotype would have in 99% a limited risk of developing T2DM, and in event of T2DM, only 1 to 2% would have a significant risk of developing atherosclerosis, which would be severe in 17%. Of the ε2ε4 genotype, 93% had a limited or even possible risk of developing T2DM, the remaining 7% had a very high risk of developing T2DM. Diabetics carrying ε2ε4 had in 7% very high risk of developing atherosclerosis. The latter had a 20% very high risk of being very severe. Subjects carrying the ε3ε4 genotype had a 67% possible or even probable risk of developing T2DM and in the event of diabetes, there was in 34% very high risk of developing atherosclerosis which will not have even the time to evolve towards severity. For subjects carrying the ε3ε3, the risk of developing T2DM and athérosclerosis was higher than that of the ε2ε3, and ε2ε4 genotypes but lower than that ε3ε4 genotype. The physio-pathological role of the APOE gene and the impacts of its polymorphisms are important in the onset and progression of type 2 diabetes mellitus.

Job Stress, Gene Polymorphism of β_2-AR, and Prevalence of Hypertension

Objective To study the interactive effect of job stress and genetic susceptibility （or gene polymorphism） on hypertension. Methods A cross-sectional epidemiological study was conducted in 452 workers from a thermal power plant in China. Extrinsic effort, occupational reward, and over-commitment were measured. Hypertensive patients were defined by three phases of screening, reexamination, and final diagnosis. β2-AR genotypes and allele frequencies at amino acid positions 16 （β2-AR-16： Arg→Gly） and 27 （β2-AR-27： Gln→Glu） were identified by PCR-RFLE Results Job stress was related with the prevalence of hypertension in males （P〈0.05）, whereas no significant relationship was found in females （P〉0.05）. Differences in genotypes and allele frequencies of the β2-AR-16 were statistically significant between the hypertension and control groups （P〈0.05）, whereas those of β2-AR-27 were not （P〉0.05）. The prevalence of hypertension was higher in individuals carrying Gly16 allele than in those carrying Arg16 allele of the high job stress group （P〈0.01 or 0.05）. Conclusion High job stress and polymorphism of β2-AR-16 have an interactive effect on the prevalence of hypertension in male workers.

Cyclooxygenase-2 polymorphisms and susceptibility to gastric carcinoma: A meta-analysis

AIM: To investigate the association of the cyclooxygenases-2 (COX-2) polymorphisms and susceptibility to gastric cancer (GC) by means of meta-analysis. METHODS: Publications addressing the association between polymorphisms of COX-2 and susceptibility to GC were selected from the MEDLINE, EMBASE and CBMdisc databases. Data was extracted from the studies by 2 independent reviewers. The meta-analyses were performed by RevMan 5.0.23. From these data, odds ratio (OR) with 95% confidence interval (CI) was calculated.RESULTS: Ten studies were retrieved reporting a total of 11 COX-2 polymorphisms. Carriers of -765C, -1195A, -1290G, *2430T alleles and *429TT genotype revealed increased risk for GC (OR = 1.71, 95% CI: 1.01-2.90, P = 0.05; OR = 1.58, 95% CI: 1.05-2.38, P = 0.03; OR = 1.55, 95% CI: 1.01-2.39, P = 0.05; OR = 2.62, 95% CI: 1.20-5.73, P = 0.02 and OR = 0.74, 95% CI: 0.59-0.95, P = 0.02, respectively). CONCLUSION: The -765C, -1195A, -1290G, *2430T alleles and *429TT genotype of COX-2 polymorphisms were determined a significant association with susceptibility to GC.

WJD 5^(th) Anniversary Special Issues(2): Type 2 diabetes Genetic polymorphisms of cytokine genes in type 2 diabetes mellitus

Diabetes mellitus is a combined metabolic disorder which includes hyperglycemia,dyslipidemia,stroke and several other complications.Various groups all over the world are relentlessly working out the possible role of a vast number of genes associated with type 2 diabetes(T2DM).Inflammation is an important outcome of any kind of imbalance in the body and is therefore an indicator of several diseases,including T2DM.Various ethnic populations around the world show different levels of variations in single nucleotide polymorphisms(SNPs).The present review was undertaken to explore the association of cytokine gene polymorphisms with T2DM in populations of different ethnicities.This will lead to the understanding of the role of cytokine genes in T2DM risk and development.Association studies of genotypes of SNPs present in cytokine genes will help to identify risk haplotype(s)for disease susceptibility by developing prognostic markers and alter treatment strategies for T2DM and related complications.This will enable individuals at risk to take prior precautionary measures and avoid or delay the onset of the disease.Future challenges will be to understand the genotypic interactions between SNPs in one cytokine gene or several genes at different loci and study their association with T2DM.

Polymorphisms of the TLR2 and TLR4 genes are associated with risk of gastric cancer in a Brazilian population

AIM： TO investigate toll-like receptor 2 （TLR2） -196 to -274 del, and TLR4 （＋896A/G rs4986790 and ＋1196C/ T rs4986791） polymorphisms at risk of chronic gastritis and gastric cancer in a Brazilian population and associ-ation of gastric lesions with risk factors such as smoking, alcohol intake and Helicobacter pylori infection.METHODS： In this casecontrol study, polymorphism at TLR2 -96 to -174 del was investigated by using the allele-specific polymerase chain reaction （PCR） method, while the PCR-restriction fragment length polymorphism technique was carried out to identify the TLR4 （rs4986790 and rs4986791） genotypes in 607 Brazilian individuals （208 with chronic gastritis-CG, 174 with gastric cancer-GC and 225 controls -C）.RESULTS： The single nucleotide polymorphisms TLR4＋1196ClT was not associated with risk of chronic gastritis or gastric cancer and the homozygous genotypes TLR4＋896GG and TLR4＋1196TF were absent in the studied population. However, the frequency of TLR2 -196 to -174 ins/del ＋ del/del and TLR4＋896AGgenotypes was significantly higher （P 〈 0.01 and P = 0.01, respectively） in the cancer group （33.4% and 11.5%, respectively） than in the control group （16.9% and 4.5%, respectively）. It was also observed that the G-C haplotype of the TLR4＋896A/G＋1196C/T （P = 0.02） and the combination of variant alleles of the TLR21TLR4＋896G （P = 0.02） are associated with susceptibility to gastric cancer. In addition, the multiple logistic regression showed that male gender [odds ratio （OR） = 2.70; 95% CI： 1.66-4.41; P 〈 0.01], alcohol intake （OR = 2.93; 95% CI： 1.76-4.87, P 〈 0.01）, TLR2 -196 to -174 del （OR = 2.64; 95% CI： 1.56-4.44; P 〈 0.01） and TLR4＋896G （OR = 3.19; 95% CI： 1.34- 7.61; P 〈 0.01） polymorphisms were associated with a higher susceptibility to developing this neoplasm.CONCLUSION： Our data indicate that T/R2 -196 to -174 del and TLR4＋896G may increase the risk of gastric cancer in a Brazilian population.

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 CYP2C19*2/*3Polymorphisms and Coronary Heart Disease

This study sought to explore the relationship between cytochrome P450 2C19(CYP2C19)*2/*3 polymorphisms and the development of coronary heart disease(CHD),and to evaluate the influence of the single nucleotide polymorphisms(SNPs)on the occurrence of adverse clinical events in CHD patients.A total of 231 consecutive patients candidate for percutaneous coronary intervention genotyped for CYP2C19*2(681G>A)and*3(636G>A)polymorphisms were enrolled.The adverse clinical events were recorded during a follow-up period of 14 months.The incidence of CHD,according to coronary angiography,was significantly higher(P=0.025)in CYP2C19*2 carriers group.Stepwise binary logistic regression analysis revealed that among factors that potentially influenced the presence of CHD(age>60 years,gender,BMI,etc.),CYP2C19*2 carriers(OR 1.94,95%CI:1.08-3.50,P=0.028)and male gender(OR 2.74,95%CI:1.58-4.76,P=0.001)were independent predictors,which were associated with the presence of CHD.The follow-up results showed that the incidence of adverse cardiovascular events within 14 months of discharge was significantly higher in the CYP2C 19*2 carriers than in the non-carriers(21.6%vs.6.3%,P=0.019).The results of the multivariate Cox proportional hazards model showed that CYP2C19*2 loss-of-flinction was the only independent factor which predicted the coronary events during the follow-up period of 14 months(OR=3.65,95%CI:1.09-12.25,P=0.036).The adverse impact of CYP2C19*2 polymorphisms was found not only in the risk of the presence of CHD,but also in the adverse cardiovascular events in CHD patients during the follow-up period of 14 months.However the same influence was not found in CYP2C19*3 mutation in Chinese Han population.

Nitric oxide synthase 2 gene polymorphisms are associated with prostatic volume in Korean men with benign prostatic hyperplasia

The precise aetiology of benign prostatic hyperplasia （BPH） remains unclear; however, it is known that immunological inflammatory processes have a role in the pathogenesis of BPH initiation and progression. Nitric oxide synthase 2 （NOS2） inducible expression is closely correlated with prostatic disease, including prostate cancer and BPH. The aim of this study was to investigate the relationship between NOS2 polymorphisms and BPH. With a cohort of 205 controls and 229 BPH subjects, we genotyped three single nucleotide polymorphisms （SNPs） in the NOS2 gene, including rs2779248 （promoter, -278 T/C）, rs 10459953 （5＇-untranslated region） and rs2297518 （exon 16, missense, Ser608Leu）, using direct sequencing and restriction fragment length polymorphism. The genotypic and allelic frequencies between control and BPH subjects were compared, and the associations among the BPH subjects were analyzed. SNPStats, SNPAnalyzer and HelixTree programmes were used to analyze SNPs. There was no association on SNPs between control and BPH subjects. When BPH subjects were analyzed, there was no association on SNPs between the low and high prostate-specific antigen groups. However, one SNP （rs 10459953, odds ratio [OR] = 0.44, 95% confidence interval [CI] = 0.29-0.65, P 〈 0.0001, in codominant model; OR = 0.23, 95% CI = 0.12-0.46, P 〈 0.0001, in dominant model; and OR = 0.46, 95% CI = 0.24-0.86, P = 0.015, in recessive model） was associated with prostatic volume in BPH. We detected a strong association in genotype frequencies of NOS2 SNP （rs10459953） between subjects with small and large prostatic volume in BPH. The result suggests that NOS2 may be associated with prostatic volume in BPH.

Tagging single nucleotide polymorphisms in the PPAR-γ and RXR-α gene and type 2 diabetes risk:a case-control study of a Chinese Han population

Peroxisome proliferator-activated receptor （PPAR-γ）,which is mainly involved in adipocyte differentiation, has been suggested to play an important role in the pathogenesis of insulin resistance and atherosclerosis. We investigated the frequencies of two common tagging polymorphisms of the PPAR-γ gene and two of PPAR-α with minor allele frequency （MAF）≥ 0.05 in the Chinese Han population and analyzed the correlation between the different genotypes and the risk of type 2 diabetes mellitus （T2DM）. TaqMan assay was performed to test the genotypes in T2DM patients （n = 1,105） and normal controls （n = 1,107）. Serum adiponectin concentration was measured by ELISA kit. The variant genotypes rs17817276GG, rs3856806CT and rs3856806CT/TT of PPAR-γ were associated with T2DM, P = 0.023,0.037 and 0.018, respectively. Furthermore, the prevalence of haplotype GT in PPAR-γ was less frequent in the case subjects （0.3%） than in the controls （1.9%） [P 0.001,OR（95%CI）=0.13 （0.06-0.31）]. Patients with genotype TT of rs3856806 had a higher serum level of adiponectin than those with the genotype CC and CT （P = 0.031 and 0.038, respectively）. There was no statistically significant difference between patients and controls in genotype distribution of rs6537944 and rs1045570 of the RXR-α gene. The present study suggests that the variant genotypes in the PPAR-γ gene could decrease the risk for the development of T2DM in the Chinese Han population.