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.

Association of single nucleotide polymorphisms of brain-derived neurotrophic factor gene and multidrug resistance 1 gene to refractory epilepsy in Chinese Han children

BACKGROUND： There are two hypotheses for the underlying cause of refractory epilepsy： ＂target＂ and ＂transport＂. Studies have shown that brain-derived neurotrophic factor （BDNF） is over-expressed in refractory epilepsy. Multidrug resistance 1 （MDR1） gene encodes for P-glycoprotein, the primary ATP-binding cassette transporter in the human body. Some single nucleotide polymorphisms of the MDR1 gene have been associated with refractory epilepsy. OBJECTIVE： To investigate the association between BDNF gene C270T polymorphism and MDR1 T-129C polymorphism with refractory epilepsy in Chinese Han children through the use of polymerase chain reaction （PCR）-restriction fragment length polymorphism analysis. DESIGN, TIME AND SETTING： A case-control, genetic association study was performed at the Central Laboratory, Third Xiangya Hospital of Central South University from June 2005 to November 2007. PARTICIPANTS： A total of 84 cases of unrelated children with epilepsy, including 41 cases of refractory epilepsy and 43 cases of drug-responsive epilepsy, were enrolled. An additional 30 healthy, Chinese Han children, whose ages and gender matched the refractory epilepsy patients, were selected as normal controls. METHODS： Venous blood was collected and genomic DNA was extracted from the blood specimens. C270T polymorphism in BDNF gene and T-129C polymorphism in MDR1 gene were genotyped using PCR-restriction fragment length polymorphism analysis. Association analysis using the Ftest and Chi-square test was statistically performed between C270T polymorphism in BDNF gene and T-129C polymorphism in MDR1 gene and refractory epilepsy. MAIN OUTCOME MEASURES： The distribution of genotypes and allele frequencies of C270T polymorphism in BDNF gene and T-129C polymorphism in MDR1 gene. RESULTS： The distribution of CC, CT, and TT genotypes, as well as C and T allele frequencies, in the BDNF gene was not significantly different between the refractory epilepsy group, drug-responsive epilepsy group, or the normal control group （P 〉 0.05）. The distribution of TT genotype and T allele frequencies of the MDR1 gene was significantly different in the refractory epilepsy group compared with the drug-responsive epilepsy and normal control groups （P 〈 0.05）. Comparison of haplotype combinations demonstrated that there were no significant differences in combinations of TT＋CC, -FI-＋CT, TC＋CC, and TC＋CT among the three groups （P 〉 0.05）. CONCLUSION： C270T polymorphism of the BDNF gene was not associated with refractory epilepsy in Chinese Han children, but T-129C polymorphism in the MDR1 gene was associated with refractory epilepsy in Chinese Han children. The TT genotype and T allele frequencies could serve as susceptibility loci for refractory epilepsy. Interactions between C270T in BDNF gene and T-129C in MDR1 gene were not observed in refractory epilepsy in Chinese Han children.

Analysis of Single Nucleotide Polymorphism in Human Paraoxonase 1 Gene(Q192R) with Matrix-assisted Laser Desorption/Ionization Time-of-flight Mass Spectrometry

Introduction Single nucleotide polymorphisms （SNPs） are the most abundant DNA markers in the human genome occurring at a frequency of one in every 500--1000 nucleotides. A variety of methods have been used for the analysis of single nucleotide polymorphisms, including restriction fragment length polymorphism （RFLP）, direct sequencing by using laser-induced fluorescence detectionTM, fluorescence energy transfer, MALDI-TOF MS combined with primer extension or invasive cleavage, and fluorescence polarization. During the past two decades, mass spectrometry has become a very popular tool in the analysis of biomolecules and is perfectly suited to the analysis of single nucleotide polymorphisms （SNPs） due to its speed, low cost, and accuracy. In this work, we used MALDI TOF mass spectrometry to detect the fragments of restriction endonuclease hydrolysis of PCR products flanking a SNP located at paraoxonase 1（Q192R）. Compared with electrophoresis, this method requires less time of analysis and possess a higher accuracy.

Significant association of a single nucleotide polymorphism in the upstream region of FGFR1OP2/wit3.0 gene with residual ridge resorption of mandible in Saudis

Residual ridge resorption(RRR)is the decrease in the jaw structure that follows tooth extraction.It is a multifactorial disorder,but reports on the associated genetic factors are scarce,particularly amongst the Saudis.This study aimed to investigate the role of single nucleotide polymorphisms(SNPs)in fibroblast growth factor receptor 1 oncogene partner 2(FGFR1OP2)in RRR development in Saudis.The study included 192 individuals(RRR=96;controls=96)attending outpatient clinics at the College of Dentistry,King Saud University.Demographic and clinical data were collected,the digital panoramic dental radiograph was obtained,and mandibular residual ridge height was measured.DNA was extracted from saliva and genotyping was conducted on“Sequenom MassARRAY iPLEX”.Genotype and allele frequencies of three SNPs were calculated and compared.The age at first diagnosis and bone height were compared in the three genotypes of each SNP.The age of the patients,age at first edentulism,and bone height ranged 21-80 years,12-70 years,and 13-34.6 mm,respectively.All three genotypes of the studied SNPs(rs2279351,rs78054962 and rs2306852)were identified.SNP rs2279351 associated significantly with RRR,and the mutant C allele was highly predisposing.No association was observed for the other two SNPs.The genotypes of all SNPs had an influence on age at first edentulism and bone height,but the results were not statistically different.Since FGFR1OP2 plays a role in the process of rapid wound healing in the oral cavity,it may be playing a role in the development of RRR by influencing the rate of resorption of the jawbone.SNP rs2279351 may alter its expression and hence RRR development.This study is limited due to small a sample size,and further large-scale studies are required to confirm this association and to consider rs2279351 as a possible marker of RRR development.

Relationship between ERCC1 (C8092A) single nucleotide polymorphism and efficacy/toxicity of platinum based chemotherapy in advanced non-small cell lung cancer patients

To assses the effect of single nucleotide polymorphism of excision repair cross-complementation group 1 C8092A on the clinical outcome and toxicity in advanced stage non-small cell lung cancer patients receiving first line platinum based chemotherapy.MethodsThis article is a review of the current research on single nucleotide polymorphism and its effect on treatment outcome and toxicity of advanced stage lung cancer.Conclusion The observations indicate that more advanced studies and trials on C8092A SNPs are needed so as to assess if it could be used as a potential biomarker in the future.

Correlation between polymorphisms in the MFN1 gene and myopia in Chinese population

AIM: To explore whether genetic variations in the MFN1 gene are associated with low to moderate myopia in Chinese population. METHODS: The case-control association analysis was used. The study included 100 independent myopia patients (-0.75 D <= spherical refraction <= -8.00 D) and 100 sex -matched healthy controls (with binocular spherical equivalent ranges between -0.50 D and +0.50 D). Four single nucleotide polymorphism (SNP) tags (rs3976523, rs13098637, rs6762399 and rs7618348) were selected for genotyping by direct sequencing. The frequencies of genotypes and their alleles were calculated based on the number of SNP genotypes in each sample. The Chi-square test was used to examine the difference in the frequency between the myopia cases and controls. RESULTS: Genotype distributions in the four SNPs were all in accordance with the Hardy -Weinberg equilibrium; analysis showed that rs13098637 was significantly associated with low to moderate myopia (P=0.003 and empirical P=0.010). There were no statistically significant differences observed for the genotype or allele frequencies of the other three SNPs between the myopia cases and controls in the Chinese population in this study. CONCLUSION: The current study has revealed that the C allele of rs13098637 in MFN1 had a significant association with low to moderate myopia.

Polymorphisms of uridine-diphosphoglucuronosyltransferase 1A7 gene in Taiwan Chinese

AIM: Single nucleotide polymorphisms (SNPs) of uridinediphosphoglucuro -nosyltransferase 1A7 (UGT1A7) gene are associated with the development of orolaryngeal cancer, hepatocellular carcinoma, and colorectal cancer. We performed this research to establish the techniques for determining UGT1A7 gene and basic data of this gene for Taiwan Chinese. METHODS: We collected blood samples from 112 healthy adults and 505 subjects carrying different genotypes of UGT1A1, and determined the promoter area and the entire sequence of UGT1A7 exon 1 by polymerase chain reaction. We designed appropriate primers and restriction enzymes to detect variant UGT1A7 genotypes found in the study subjects. RESULTS: Six SNPs at nucleotides 33, 387, 391, 392, 622, and 756 within the coding region of UGT1A7 exon 1 were found. The incidence of UGT1A7*l/*2 (N129R131W208/ K129K131W208) was predominant (35.7%) while that of UGT1A7 *3/*3 (K129K131R208/K129K131R208) was the least (2.7%). The allele frequency of UGT1A7*3, which exists in a considerable proportion of Caucasians (0.361) and Japanese (0.255), was identified only to be 0.152 in our study subjects. A novel variation at nucleotide -57 in the upstream was found, which was associated with SNPs at nucleotides 33, 387, 391, 392, and 622 in one of the variant haplotypes. The nucleotide changes at positions 387, 391, 392 and 756 were in linkage in another variant haplotype. The allele frequency of UGT1A7*3 was 0.018, 0.158, 0.242, 0.433, and 0.920 in subjects carrying wild, A(TA)6TAA/A(TA)7TAA, A(TA)7TAA/A(TA)7TAA, 211G/211A, and 211A/211A variants of UGT1A1 gene, respectively. By using natural or mutagenesis primers, we successfully detected the variations at nucleotides -57, 33, 387, and 622 with the restriction enzymes HpyCH4 Ⅳ, TaqⅠ, AflⅡ, and Rsa Ⅰ, respectively. CONCLUSION: The results indicate that the allele frequencies of UGT1A7 gene in Taiwan Chinese are different from those in Caucasians and Japanese. Carriage of the nucleotide 211- variant UGT1A gene is highly associated with UGT1A7*3. The restriction-enzymedigestion method for the determination of nucleotides-57 (or 33, or 622) and 387 can rapidly identify genotypes of UGT1A7 in an individual.

Associations between IL-1RN variable number of tandem repeat, IL-1β (-511) and IL-1β (+3954) gene polymorphisms and urolithiasis in Uighur children of China

Objective:Interleukin-1(IL-1)is a pro-inflammatory cytokine which may be related to urolithiasis.Genetic polymorphisms of the interleukin-1beta(IL-1β)have been proposed as markers for urolithiasis in some areas.Due to the high incidence of urolithiasis in Uighur children(Xinjiang,China)and existence of ethnic difference,our aim is to explore the potential of IL-1 gene polymorphisms and urolithiasis among these children.Methods:Genomic DNA extracted from peripheral blood of 115 patients and 98 controls were used for genotype polymorphisms analyses.IL-1 receptor antagonist(IL-1RN)gene variable number of tandem repeat(VNTR)gene polymorphisms were analyzed by PCR method.PCR-based restriction analysis was done for the IL-1β(-511)and IL-1β(+3954)gene polymorphisms by endonucleases Ava I and Taq I,respectively.The genotype distribution,allele frequencies,carriage rate,and haplotype frequencies were statistically analyzed.Results:No significant differences were observed in genotypic frequencies between pediatric urolithiasis patients and control group for IL-1RN gene(χ^(2)=1.906,p=0.605),IL-1β(-511)gene(χ^(2)=0.105,p=0.949),or IL-1β(+3954)gene(χ^(2)=3.635,p=0.169).There were yet no significant differences of the allele frequencies of IL-1RN VNTR gene(p=0.779),IL-1β(-511)gene(p=0.941),and IL-1β(+3954)gene(p=0.418)in the case and control groups,as well as the carriage rate and haplotype of them(all p>0.05).Conclusions:The associations between IL-1RN VNTR,IL-1β(-511)and IL-1β(+3954)genes polymorphisms and urolithiasis were not significant in Uighur children.The results need to be confirmed in studies with larger population sample size,as well as in other ethnic groups.

中国家驴TYRP1基因第二内含子多态性分析

为了探究TYRP1基因对中国家驴毛色的影响,试验采集410只不同毛色中国家驴的血液样本,采用聚合酶链式反应及单链构象多态性(polymerase chain reaction and single-strand conformation polymorphism, PCR-SSCP)方法检测中国家驴TYRP1基因第二内含子中的单核苷酸多态性(single nucleotide polymorphism, SNP)位点,对不同毛色中国家驴个体进行基因分型,并计算基因型频率和等位基因频率,分析TYRP1基因第二内含子多态性与中国家驴不同毛色之间的关系。结果表明:在中国家驴TYRP1基因第二内含子中检测到1个SNP位点(g.1 702A→G),该位点存在AA、AG、GG三种基因型;乌头、黑三粉、青三粉、灰三粉、白色和白化家驴的优势等位基因均为A。乌头、黑三粉和青三粉均为AA基因型频率最高,GG基因型频率最低;灰三粉为AA基因型频率最高,AG基因型频率最低(0)。在乌头、黑三粉、青三粉、灰三粉家驴中,AA基因型频率为灰三粉最高,然后依次为青三粉、黑三粉和乌头;以黑毛色为主色调的家驴(乌头、黑三粉、青三粉)GG基因型频率低于以灰毛色为主色调的家驴(灰三粉),有白毛混杂的黑三粉和青三粉的GG基因型频率低于纯黑的乌头。样本中的白色家驴和白化家驴各有2头,其基因型均为AA纯合子。说明随着中国家驴黑色被毛比例的增加,TYRP1基因g.1 702A→G位点的AA基因型频率逐渐降低,推测该位点可能与中国家驴毛色性状有关。

子宫内膜异位症不同r-AFS分期患者血清Furin,TGF-β,VEGF,netrin-1水平表达及Furin基因P1启动区r2071410 C/T位点多态性分析

目的了解子宫内膜异位症(endometriosis,EMT)不同r-AFS分期患者血清弗林蛋白酶(Furin)、肿瘤生长因子-β(tumor growth factor-β,TGF-β)、血管生长因子(vascular endothelial growth factor,VEGF)及神经轴突导向因子-1(neuron towards axon guidance factor-1,netrin-1)水平表达及Furin基因P1启动区r2071410 C/T位点多态性,探讨其与深圳地区EMT发病的相关性。方法选取2021年5月~2023年1月深圳市龙华区人民医院确诊的EMT患者102例为EMT组,并根据r-AFs分期法将EMT组分为I~II期和III~IV期。同时收集同期非EMT患者78例为对照组。采用酶联免疫吸附法(enzyme-linked immunosorbent assay,ELISA)检测血清Furin,TGF-β,VEGF及netrin-1水平,并采用反转录-实时荧光定量聚合酶链反应法(reverse transcription-real time quantitative polymerase chain reaction,RT-qPCR)分析Furin基因P1启动区r2071410 C/T位点多态性。结果EMT组患者血清Furin(140.84±47.02pg/ml),TGF-β(376.46±82.36ng/L)和VEGF水平(167.67±53.02ng/L)明显高于对照组(55.49±13.67pg/ml,216.37±15.04ng/L,102.27±8.45ng/L),而netrin-1水平(48.37±15.20pg/ml)明显低于对照组(165.85±15.63pg/ml),差异具有统计学意义(t=28.409,20.347,16.915,36.653,均P<0.05)。III~IV期患者血清Furin(192.41±20.62pg/ml),TGF-β(452.61±72.03ng/L)和VEGF水平(201.84±28.01ng/L)明显高于I~II期(78.05±16.54pg/ml,283.75±56.92ng/L,126.07±19.35ng/L),而netrin-1水平(37.95±11.34pg/ml)明显低于I~II期(61.05±9.52pg/ml),差异有统计学意义(t=31.071,18.054,19.183,21.625,均P<0.05)。经Pearson/Spearman相关性分析结果显示,Furin与TGF-β,VEGF水平及临床分期呈正相关(r=0.6149,0.7526,0.7905,均P<0.05),而与netrin-1水平呈负相关(r=-0.6701,均P<0.05)。EMT组患者Furin基因P1启动区r2071410 C/T位点TT基因型和T等位基因频率(42.16%,55.39%)明显高于对照组(7.69%,19.87%),且III~IV期TT基因型和T等位基因频率(51.79%,65.18%)比I~II期(30.43%,43.48%)明显升高,差异具有统计学意义(χ^(2)=26.500,46.472,4.721,9.626,均P<0.05)。EMT组不同基因型患者血清Furin水平差异具有统计学意义(F=51.286,P<0.001),其中TT基因型患者血清Furin水平(216.29±68.53pg/ml)明显高于CC(83.04±21.37pg/ml)和CT基因型(89.18±20.95pg/ml),差异具有统计学意义(t=27.146,25.719,均P<0.01),但CC与CT基因型之间差异无统计学意义(t=1.326,P>0.05)。结论EMT患者血清Furin水平明显升高,且与TGF-β,VEGF,netrin-1水平及临床分期呈一定相关性;同时Furin基因P1启动区r2071410 C/T位点呈多态性分布,其中TT基因型患者血清Furin水平升高更为明显,可能与深圳地区EMT发病有关。

MAX二聚化蛋白1基因rs12475412和rs7349311多态性与中国汉族人群缺血性脑卒中及其中医证候的相关性

目的探索MAX二聚化蛋白1(MXD1)基因rs12475412、rs7349311多态性与中国汉族人群缺血性脑卒中(IS)及其中医证候的相关性。方法选取2016年1月至2019年12月于广西中医药大学第一附属医院脑病科就诊的774例IS患者作为观察组,选取同期本院社区体检中心健康体检者或外科等科室病情较轻的外伤患者793例作为对照组。使用MassARRAY单核苷酸多态性技术进行基因分型检测,应用PLINK软件进行遗传关联分析统计。结果观察组与对照组rs12475412、rs7349311位点的基因型频率分布差异均无统计学意义(均P>0.05)。校正年龄后,MXD1基因rs12475412、rs7349311多态性与中国汉族女性IS患者血瘀证发生风险显著相关(rs12475412加性模型、显性模型、隐性模型的比值比分别为1.033、1.031、1.034,rs7349311显性模型、隐性模型的比值比分别为1.034、1.033,均P<0.05),并与气虚证发生风险显著相关(rs12475412加性模型、显性模型、隐性模型的比值比分别为1.036、1.036、1.036,rs7349311加性模型、显性模型、隐性模型的比值比分别为1.043、1.043、1.044,均P<0.05)。但MXD1基因rs12475412、rs7349311多态性与中国汉族男性IS各中医证候均无明显相关性(均P>0.05)。在校正年龄后,MXD1基因rs12475412、rs7349311多态性与中国汉族女性IS血瘀证和气虚证患者空腹血糖、D-二聚体、凝血酶时间水平显著相关(均P<0.05)。结论MXD1基因多态性可能通过参与调控血糖代谢、凝血功能而影响中国汉族女性IS血瘀证和气虚证的发生发展。

PD-1基因单核苷酸多态性与肝细胞癌血液学分子标志物的关联性研究

目的 探讨程序性死亡受体1(programmed death receptor 1,PD-1)基因单核苷酸多态性与肝细胞癌血液学分子标志物的关联性研究。方法 选择2021年1-12月南通大学附属医院介入放射科收治的165例新发肝癌患者作为入组对象,提取基因组DNA,采用Panel高通量数据分析进行PD-1基因分型,分析各基因型与肝癌血液学分子标志物的关联性。结果 AFP的不同分组情况,在rs10204525、rs2227982、rs36084323基因分型情况,各位点突变基因型在AFP不同分组上差异无统计学意义(P>0.05);PIVKA-Ⅱ不同分组上,对于rs2227982分组,野生型CC、杂合突变型CT、纯合突变型TT、突变型CT+TT在PIVKA-Ⅱ(-)与PIVKA-Ⅱ(+)比较,差异无统计学意义(P> 0.05),而对rs2227982分组,其中杂合突变型AG(34例vs19例)、纯合突变型AA在PIVKA-Ⅱ(-)与PIVKA-Ⅱ(+)(30例vs15例)比较差异有统计学意义(χ^(2)=3.125,7.158P<0.05);rs10204525、rs36084323分组,CT、TT、CT+TT与PIVKA-Ⅱ指标无明显关联(P>0.05)。结论 PD-1基因rs36084323位点单核苷酸多态性与异常凝血酶原指标之间存在一定关联。

血小板内皮聚集受体1基因单核苷酸多态性与癫痫持续状态后患者认知功能的关系

目的探讨血小板内皮聚集受体1(PEAR1)基因单核苷酸多态性与癫痫持续状态后患者认知功能的关系。方法选择2020年1月至2022年1月安阳市人民医院收治的60例癫痫持续状态患者为研究对象(观察组)。另选择60例同期来院进行体检的健康志愿者为对照组。采用简易智力状态检查量表(MMSE)评估2组受试者的认知功能,并检测所有受试者PEAR1基因中rs12041331位点基因分型。根据MMSE评分结果将观察组患者分为认知功能正常组(n=40)和认知功能障碍组(n=20)。收集所有患者的临床资料,采用单因素和多因素logistic回归分析影响癫痫持续状态后患者认知功能的危险因素。结果观察组患者PEAR1基因rs12041331位点AA、GG、GA基因型分布频率与对照组比较差异有统计学意义(P<0.05)。观察组患者MMSE评分显著低于对照组(P<0.05)。单因素分析结果显示,认知功能障碍组患者的性别、年龄、发作类型、文化程度、服用抗癫痫药物种类、家族史与认知功能正常组比较差异无统计学意义(P>0.05);认知功能障碍组与认知功能正常组患者的PEAR1基因rs12041331位点基因分型、每个月发作频率、病程、起病年龄和MMSE评分比较差异有统计学意义(P<0.05)。多因素logistic回归分析结果显示,PEAR1基因rs12041331位点AA基因型、每个月发作频率>4次、病程时间长、起病年龄小、低MMSE评分是癫痫持续状态后患者发生认知功能障碍的危险因素(P<0.05)。结论PEAR1基因rs12041331位点AA基因型是癫痫持续状态后患者发生认知功能障碍的危险因素,携带AA基因型的癫痫持续状态患者更易发生认知功能障碍。

PAI-1 genetic polymorphisms influence septic patients’outcomes by regulating neutrophil activity

Background:Plasminogen activator inhibitor-1(PAI-1)plays an important role in the pathophysiology of sepsis,but the exact mechanism remains debatable.In this study,we investigated the associations among the serum levels of PAI-1,the incidence of 4G/5G promoter PAI-1 gene polymorphisms,immunological indicators,and clinical outcomes in septic patients.Methods:A total of 181 patients aged 18-80 years with sepsis between November 2016 and August 2018 in the intensive care unit in the Xinhua Hospital were recruited in this retrospective study,with 28-day mortality as the primary outcome.The initial serum level of PAI-1 and the presence of rs1799768 single nucleotide polymorphisms(SNPs)were examined.Univariate logistic regression and multivariate analyses were performed to determine the factors associated with different genotypes of PAI-1,serum level of PAI-1,and 28-day mortality.Results:The logistic analysis suggested that a high serum level of PAI-1 was associated with the rs1799768 SNP of PAI-1(4G/4G and 4G/5G)(Odds ratio[OR]:2.49;95%confidence interval[CI]:1.09,5.68).Furthermore,a high serum level of PAI-1 strongly influenced 28-day mortality(OR 3.36;95%CI 1.51,7.49).The expression and activation of neutrophils(OR 0.96;95%CI 0.93,0.99),as well as the changes in the expression patterns of cytokines and chemokine-associated neutrophils(OR:1.00;95%CI:1.00,1.00),were both regulated by the genotype of PAI-1.Conclusions:Genetic polymorphisms of PAI-1 can influence the serum levels of PAI-1,which might contribute to mortality by affecting neutrophil activity.Thus,patients with severe sepsis might clinically benefit from enhanced neutrophil clearance and the resolution of inflammation via the regulation of PAI-1 expression and activity.

PDZK1基因启动子区rs12129861位点基因多态性与新疆汉族男性人群痛风发病的关系

目的了解PDZ蛋白激酶1(PDZK1)基因启动子区rs12129861(A/G)位点的基因型和基因频率与新疆地区汉族男性人群痛风发病的关系。方法收集汉族男性痛风患者(痛风组)和同时期体检健康者(对照组)的血样,采用多重荧光PCR技术检测PDZK1基因启动子区rs12129861(A/G)位点的基因型。比较两组rs12129861(A/G)位点的基因型分布及基因频率以及不同rs12129861(A/G)位点的基因型人群血清尿酸浓度。选择KpnI、XhoI双酶切位点,构建含rs12129861(A/G)位点的pGL3-promotor荧光素酶表达载体,采用双荧光素酶报告基因实验证实启动子区rs12129861(A/G)位点是否影响荧光素酶基因的表达。结果PDZK1基因启动子区rs12129861(A/G)位点基因型分布符合Hardy-Weinberg平衡性检验(P>0.05),该位点稳定遗传具有群体代表性。痛风组和对照组PDZK1基因启动子区rs12129861(A/G)位点AA、GA、GG基因型分布频率差异有统计学意义(χ^(2)=14.633,P<0.01),等位基因A和G分布频率的差异有统计学意义(χ^(2)=14.236,P<0.01),其中痛风组等位基因G的分布频率高于对照组,OR值为1.661。rs12129861(A/G)位点基因型为A/A与G/G人群间、G/A与G/G人群间血清尿酸浓度比较,P<0.05,其中基因型为G/G的人群血尿酸浓度大于基因型A/A、G/A人群。双荧光素酶实验结果显示,rs12129861(A/G)具有增强子功能,rs12129861(G)重组质粒的荧光素酶报告基因表达水平低于rs12129861(A)重组质粒(P<0.05)。结论PDZK1基因启动子区rs12129861位点的基因型和基因频率与新疆汉族男性痛风有关,等位基因G可能是痛风发病的危险因素。

Deleterious Nonsynonymous SNP Found within <i>HLA-DRB1</i>Gene Involved in Allograft Rejection in Sudanese Family: Using DNA Sequencing and Bioinformatics Methods

Renal transplantation provides the best long-term treatment for chronic renal failure. Single-nucleotide polymorphisms (SNPs) play a major role in the understanding of the genetic basis of many complex human diseases. Also, the genetics of human phenotype variation could be understood by knowing the functions of these SNPs. It is still a major challenge to identify the functional SNPs in a disease-related gene. This work explored how SNPs mutations in HLA-DRB1 gene could affect renal transplantation rejection. This study was carried out in Ahmed Gasim Hospital, Renal Dialysis Center during the period, from September 2012 to November 2013. Blood samples from five Sudanese patients (different families) with known renal transplantation rejection were collected before hemodialysis, furthermore one blood sample for control. DNA sequences results and detected SNPs were analyzed using bioinformatics tools (BLAST, SIFT, nsSNP Analyzer, PolyPhen, I-mutant, BioEdit, CPH, Chimera, Box shade and Project Hope). In addition, international databases were used for datasets [NCBI, Uniprot]. Results showed that, three SNPs were detected;two of three SNPs were predicted as tolerant or benign (rs1059575, novel) and one was deleterious (rs17885437). This study concluded that the identification of pathological SNPs could be an answer to unknown causes for a lot of organ transplantation rejection cases.

PARP-1基因多态性与妊娠期高血压的相关性及潜在分子机制研究

目的探讨多聚ADP核糖转移酶(PARP-1)基因多态性与妊娠期高血压(HDP)的相关性,以及HDP的潜在发病机制。方法纳入2021年8月至2022年6月在该院就诊的80例HDP孕妇作为HDP组,以及同期80例健康孕妇作为对照组。对比两组临床资料,采用荧光定量PCR法检测外周血单个核细胞PARP-1、TRL7、MyD88和核因子-κB(NF-κB)mRNA水平及PARP-1基因不同位点的单核苷酸多态性,采用Western blotting法检测外周血单个核细胞PARP-1、TRL7、MyD88和NF-κB蛋白相对表达量;Logistic回归模型分析PARP-1单核苷酸多态性与HDP的相关性;采用Pearson相关性分析PARP-1 mRNA和蛋白表达与NF-κB通路蛋白表达的相关性。结果HDP组血管内皮生长因子受体-1(sFlt-1)、sFlt-1/胎盘生长因子(sFlt-1/PLGF)水平,PARP-1、TRL7、MyD88和NF-κB mRNA水平,以及PARP-1、TRL7、MyD88和NF-κB蛋白相对表达量高于对照组,PARP-1基因rs1805414位点CC基因型高于对照组,差异有统计学意义(P<0.05);Logistic回归模型分析显示,sFlt-1/PLGF(OR=1.236)、PARP-1 mRNA(OR=107.998)及PARP-1基因rs1805414位点CC基因型(OR=3.788)是HDP患者发生子痫前期(PE)的独立危险因素(P<0.05);Pearson相关性分析显示,PARP-1 mRNA水平与TRL7、MyD88和NF-κB mRNA水平呈正相关(r=0.782、0.688、0.903,均P<0.05);PARP-1蛋白相对表达量与TRL7、MyD88和NF-κB蛋白相对表达量呈正相关(r=0.833、0.845、0.907,均P<0.05)。结论PARP-1表达水平及多态性与HDP发病密切相关,特别是rs1805414位点CC突变可作为HDP遗传易感性的敏感指标;NF-κB信号通路在PARP-1参与HDP发病中发挥了重要的作用。

长链非编码RNA配对盒基因8反义RNA1在恶性肿瘤中的研究进展

长链非编码RNA(lncRNA)是一类长度大于200个核苷酸的RNA转录本。配对盒基因8反义RNA1(PAX8-AS1)是lncRNA的一种,在甲状腺癌、乳腺癌、子宫内膜癌、急性白血病、肾上腺皮质癌等多种恶性肿瘤中异常表达,通过作为竞争性内源RNA和其单核苷酸多态性等机制调节癌细胞的增殖、凋亡、侵袭和耐药性,对癌症的诊断、治疗及预后具有非常重要的价值。本文就lncRNA PAX8-AS1在恶性肿瘤中的作用机制及潜在应用进行综述。

HLA-DRB1基因多态性与高血压肾病的关系

目的:探讨HLA-DRB1基因rs2308765和rs9269186 2个位点的单核苷酸多态性(SNPs)与高血压肾病的关系,为高血压肾病的遗传学机制研究提供理论依据。方法:采用病例-对照的研究方法,收集45例高血压肾病患者和52例对照为研究对象。应用聚合酶链反应-连接酶检测反应(PCR-LDR)技术进行SNPs突变检测。采用拟合优度χ2检验分析基因型分布是否符合Hardy-Weinberg平衡定律,病例组与对照组基因型和等位基因频数分布分析应用χ2检验。结果:rs2308765位点呈G/T二态性,本研究群体中出现G/G和G/T 2种基因型,病例组和对照组rs2308765位点的基因型和等位基因分布差异无统计学意义(P>0.05);rs9269186位点呈C/G二态性,本研究群体中出现了C/C、G/G和C/G 3种基因型,病例组和对照组的rs9269186位点的基因型分布和等位基因分布差异有统计学意义(P<0.05)。结论:rs2308765位点的SNPs可能与高血压肾病无关,而rs9269186位点的SNPs可能与高血压肾病有关。

MPO、NQO1、GSTP1和UGT1A6基因多态与慢性苯中毒遗传易感性关系

目的探讨MPO、NQO1、GSTP1和UGT1A6基因多态与慢性苯中毒易感性的关系。方法采用病例-对照研究，以268名苯中毒工人为病例组，268名接触苯而没有中毒表现的工人为对照组。应用TaqManPCR分析技术判定MPO（rs7208693），NQO1（rs1800566），GSTP1（rs947894）和UGT1A6（rs6759892，rs1105879，rs4124874，rs3755319，rs887829和rs4148323）基因型。结果携带GSTP1基因rs947894G等位基因个体患慢性苯中毒的危险性比AA基因型个体降低0．657倍（95％CI0．434～0．994，P=0．046）；携带MPO基因rs7208693A等位基因人群中，UGT1A6 rs6759892 G等位基因个体发生慢性苯中毒的危险性是TT基因型的2．702倍（P=0．024），UGT1 A6 rs1105879 C等位基因个体发生慢性苯中毒的危险性是TT型的2．619倍（P=0．035）。在饮酒人群中，携带NQO1基因rs1800566 TT基因型个体慢性苯中毒的发病风险较携带CC和CT基因型个体增加9．000倍（95％CI，1．460～55．478，P=0．021）；在吸烟人群中，带NQO1基因rs1800566TT基因型个体慢性苯中毒的发病风险较携带CC和CT基因型个体增加7．000倍（95％CI，1．555～31．575，P=0.012）。单倍型分析显示，本人群携带UGT1A6基因TACGGG单倍型个体慢性苯中毒的发病风险是携带TAATGG单倍型个体的1．446倍（OR=1．446，95％CI，1．005～2．080，P=0．046）。结论同时携带MPO基因rs7208693 A和UGT1A6基因rs6759892 G或rs1105879 C等位基因型个体对苯中毒易感；携带NQO1基因rs1800566 TT基因型且同时吸烟或饮酒的个体对苯中毒易感；携带UGT1A6基因TAATGG单倍型个体可增加慢性苯中毒的发病风险；GSTP1基因多态与慢性苯中毒遗传易感性的关系仍需进一步研究。