中国北方人群谷胱甘肽转硫酶P1基因多态性及其与胃癌遗传易感性的关系

为了分析中国北方人群谷胱甘肽转硫酶P1基因(glutathione-S-transferase P1, GSTP1)多态性分布, 同时探讨GSTP1基因多态性及其与幽门螺杆菌(H. pylori)既往感染联合作用对胃癌发病风险的影响, 采用多聚酶链反应-限制性片段长度多态性(PCR-RFLP)技术检测1,612例外周血DNA GSTP1的多态性; 采用ELISA方法检测血清H. pylori IgG。结果显示, (1) 中国北方人群GSTP1基因Val等位基因分布频率为22%, 胃癌高、低发区GSTP1 Val等位基因分布频率有显著性差异(0.23/0.20); (2) 以Ile/Ile基因型为参照组与其他两种基因型比较进行胃癌的风险分析, 结果显示携带Val/Val基因型的个体患胃癌的危险性最大, 其OR为5.588 (3.256 ~ 9.591); 携带Val等位基因的个体患胃癌危险性是非携带Val等位基因个体的1.587倍; (3) 以H. pylori IgG(-)并携带GSTP1基因纯合野生型(Ile/ Ile)的个体为参照, H. pylori IgG(+)并携带纯合多态基因型(Val/Val)的个体患胃癌的风险最高, OR为17.571(6.207 ~ 49.742)。说明GSTP1 Val等位基因的分布存在人群及地区差异。携带GSTP1 Val等位基因的个体胃癌发病风险增高。GSTP1 Val等位基因纯合型与H. pylori感染对于胃癌的发生具有交互作用。     

中国云南汉族群体VKORC1基因多态性研究

目的：探讨云南汉族人群维生素K环氧化物还原酶亚单位1（VKORC1 ）基因多态性,并与国内外群体进行比较。方法：采集280云南汉族心瓣膜置换术病人外周血,获得基因组DNA,用PCR-RFLP 方法分析VKORC1-1639G/A,1173C/T,3730A/G 的基因多态性。结果：对于VKORC1-1639G/A,共检出222 (79.3%)名AA纯合子,8(2.8%)名GG纯合子,50(17.9%)名AG杂合子;对于VKORC1-1173C/T,检出224 (80.0%) 名纯合子TT,56 (20.0%)名杂合子CT,未检出CC 基因型;对于VKORC1 3730 A/G,共检出30(10.7%)名AA 基因型,205 (73.2%)名GG 基因型,45 (16.1%)名AG 基因型。与不同群体相比,各位点差别不一。结论：与其他 群体相比,云南汉族人群VKORC1-1639G/A,1173C/T,3730A/G 基因位点具有自己的遗传多态性,其基因多态性在临床药物应 用（如华法林）治疗中具有非常重要的意义。     

CTLA-4+49A>G基因多态性与结直肠癌的相关性研究

目的:探讨细胞毒性T淋巴细胞相关抗原-4(CTLA-4)+49 AG位点多态性与结直肠癌发生的相关性,为早期预测结直肠癌的发生提供临床参考依据。方法:选取结直肠癌病例231例未实验组和正常健康体检者325例为对照组,取其空腹外周静脉血提取DNA后,采用聚合酶链式反应(PCR)技术对CTLA-4基因第1外显子区+49位点DNA进行扩增,产物用限制性片段长度多态性(RFLP)方法检测CTLA-4第1外显子区+49AG位点的多态性,比较两组杂合子AG和纯合子AA、GG基因型发生的频率、A等位基因与G等位基因的分布,分析CTLA-4+49 AG位点多态性与结直肠癌发生的相关性。结果:两组间CTLA-4基因外显子1区+49AG位点杂合子AG和纯合子AA、GG基因型发生的频率以及A等位基因与G等位基因的分布比较差异均无统计学意义(P0.05)。结论:CTLA-4基因外显子1区+49 AG基因多态性与我省汉族人群结直肠癌的发病无显著相关性。     

绝经后女性CYP19基因Val80及OPG基因A163G多态性与骨密度的相关性研究

探讨细胞色素P450 19 (CYP19) 基因Val80多态性及护骨素(OPG) 基因A163G多态性与绝经后女性骨密度 (BMD) 的关系。随机选择居住在重庆的绝经后女性200例, 采用多聚酶链反应-限制性片段长度多态性法检测Val80及A163G多态性, 采用Norland公司XR-46系列双能X线骨密度仪测量股骨近端及腰椎BMD。 200名绝经后女性中Val80基因型GG、GA及AA的频率分别为19.5％、44.5％及36.0％; A163G基因型GG、GC 及CC的频率分别为: 13.0％, 42.0％及45.0％; 基因型频率分布均符合Hardy-Weinberg平衡 (P＞0.05)。协方差分析及多元逐步回归分析显示CYP19基因第3外显子Val80多态性与绝经后女性BMD无相关性 (P＞0.05)。除大转子外, A163G位点AG/GG/AG+GG基因型者股骨颈、Ward’s三角及腰椎BMD均较AA基因型者低, A163G基因型与股骨颈、Ward’s三角及腰椎BMD有相关性 (P＜0.05)。OPG基因启动子区A163G多态性分布存在明显的种族差异, 且与绝经后女性BMD有一定关联, AA型对BMD具有一定的保护作用, G等位基因是BMD降低的危险因素。     

用DHPLC法研究细胞周期蛋白D1的多态性与NPC遗传易感性之间的关系

细胞周期蛋白D1是一个关键的细胞周期调节因子和候选的原癌基因 ,其失调参与多种肿瘤 ,包括鼻咽癌的发生。由于细胞周期蛋白D1的基因CCND1第 4外显子存在单个核苷酸多态A/G(A870G) ,因此可产生两种不同的转录本。有报道表明CCND1的基因型与某些肿瘤的临床表型相关。为研究细胞周期蛋白D1的基因型对中国南方散发性鼻咽癌遗传易感性是否存在影响 ,用变性高效液相色谱法 (DHPLC)和DNA测序的方法对 84例鼻咽癌患者和 91例对照的PCR产物进行细胞周期蛋白D1的基因分型。对病例组与对照组基因频率的分布分别进行Hardy Weinberg平衡检验 ,两组间基因频率的差异用 χ2 检验进行比较。结果发现 :在鼻咽癌患者中 ,细胞周期蛋白D1基因型为AA型的 (占 2 0 .2 4% )显著低于正常对照 (占38.46 % ) ,而基因型为GG型和AG型的则显著高于对照 (χ2 =6 .946 ,Pcorrected =0 .0 16 ,OR =2 .46 3,95 %CI =1.2 49～4.85 9)。这表明细胞周期蛋白D1基因的A/G多态性与鼻咽癌的遗传易感性相关 ,在鼻咽癌患者中GG和AG型基因型显著高于健康对照     

猪整合素β1基因CRS-PCR多态性与产仔数的关联性分析

文章采用CRS-RFLP技术对长白猪、大白猪和杜洛克猪3个品种的整合素β1基因第5外显子T32207C位点及第7外显子A35230G位点进行单核苷酸多态性分析,并将基因多态性与猪的产仔数进行关联分析。结果表明:32207多态位点的基因型效应对3个品种的总产仔数(TNB)和产活仔数(NBA)影响均不显著;35230多态位点的基因型效应对大白猪和长白猪头胎、二胎及所有胎次的TNB和NBA的影响达到显著(P<0.05)或者极显著水平(P<0.01),基因型GG、AG与AA对产仔数的影响存在差异,其效应为GG,AG>AA。可见整合素β1基因35230位点的G等位基因对大白猪和长白猪的产仔数性状有显著影响。     

Ⅰ型干扰素受体启动子多态性与慢性乙型肝炎易感性的相关性研究

目的 研究Ⅰ型干扰素受体启动子(IFNAR1)的基因多态性在不同个体间的差异,以及它们与慢性乙型肝炎病毒(HBV)感染之间的相关性。方法 对320例慢性乙型肝炎患者、148例自发康复者、148例健康对照和114例正常高加索人的IFNAR1进行基因分型,分析基因的多态性与慢性HBV感染的易感性之间的相关性;构建IFNAR1启动子-荧光素酶报告基因载体,比较不同IFNAR1启动子变异体的转录活性。结果 在-568,-408,-77和-3位点发现基因多态性,其中-568和-77位点,以及-408和-3位点之间存在等位基因连锁。相关性分析结果表明,-568G、-408C和单体型-568G/-408C/-3C/-77(M)与病毒清除有关,-568C、-408T和单体型-568C/-408T/-3T/-77(L)与HBV感染的慢性化有关。启动子-荧光素酶报告基因载体的检测显示,-408和(或)-3位点的多态性可影响调节IFNAR1启动子的转录水平,而-568位点的多态性总体上对转录活性无明显的影响。-77(9)在高加索人中明显多见,携带这一基因型启动子的转录活性明显高于其他基因型启动子的转录活性。结论 IFNAR1的基因多态性与慢性HBV感染的易感性有相关性。     

白介素18启动子区基因多态性与儿童EV71感染相关性研究

目的:研究白介素18基因启动子多态性与儿童EV71感染遗传易感性的关系.方法:收集EV71感染患儿177例,单纯HFMD组127例,HFMD并脑炎组50例,提取外周血DNA,用序列特异性引物-聚合酶链反应(SSP-PCR)技术及基因测序法检测IL-18启动子区-137G/C、-607A/C位点的基因多态性.结果:EV71感染患儿与健康儿童IL-18-607基因型以CA为主,AA、CC次之,EV71感染患儿AA基因型、A等位基因分布频率显著高于健康儿童.EV71感染HFMD并脑炎组患儿AA基因型分布显著高于单纯HFMD组患儿,差异有统计学意义.EV71感染患儿与健康儿童IL-18-137基因型以CC为主,CG次之,GG占少数.该位点基因型及等位基因在EV71感染组与健康儿童、单纯HFMD与HFMD并脑炎组的分布无显著差异.结论:IL-18基因多态性与EV71感染相关,IL-18-607AA基因型、A等位基因携带儿童更易感染EV71病毒,且AA基因型患儿易并发脑炎,-607AA基因型可能为EV71感染的易感基因型.-137C/G位点基因多态性与EV71感染无相关性.     

年轻母亲叶酸代谢基因多态性与唐氏综合征发生的关系

为探讨年轻母亲叶酸代谢相关基因MTHFR 677C>T、MTRR 66A>G、RFC-1 80G>A和MTR 2756A>G多态性与唐氏综合征(Down syndrome, DS)发生的关系, 采用随机病例-对照研究设计, 应用PCR-RFLP方法检测60例DS患儿的母亲与68例正常生育女性的基因型。经χ² 检验, MTHFR基因T等位基因频率在病例组和对照组中差异有统计学意义(P<0.05), 而MTRR、MTR和 RFC-1等位基因频率差异无统计学意义。Logistic回归分析显示: 携带MTHFR TT基因型的母亲孕育DS患儿的风险显著增加(OR=3.51, 95% CI=1.30~9.46, P<0.05), 而杂合子CT以及CT合并TT基因型与DS发生风险无显著关联; 携带MTRR GG基因型的母亲孕育DS患儿的风险增加3.16倍(OR=3.16, 95% CI=1.20~8.35, P<0.05), 而RFC-1和MTR突变基因型与DS发生风险无显著关联; MTHFR(CT+TT)/MTRR GG、MTHFR (CT+TT)/ RFC-1 AA、MTHFR CC / MTR (AG +GG)、 MTHFR (CT+TT)/MTR AA、MTRR GG/MTR AA和RFC-1 AA / MTR AA联合基因型与DS发生风险显著相关。结果表明, 年轻女性MTHFR 677C>T、MTRR 66A>G位点变异是孕育DS患儿的独立风险因子, 尚不能认为RFC-1 80G>A、MTR 2756A>G多态性与DS发生相关, 而基因与基因多态位点之间存在交互和修饰效应。     

单核细胞趋化蛋白-1基因多态性与癌易感性的Meta分析

探讨单核细胞趋化蛋白-1(MCP-1)2518 A/G基因多态性与癌易感性的关联情况。计算机检索相关数据库,收集自建库至2016年12月国内外已发表的有关MCP-1-2518 A/G基因多态性与肿瘤易感性关联的研究。共纳入30项病例对照研究(包括5 602例患癌患者和6 500例健康对照人群)。采用Stata 12.0软件进行统计学分析。Cochran Q检验和I2检验对各研究进行异质性检验,计算合并比值比(OR值)及其95%可信区间(95%CI)以评价关联性,Begg's test和Egger's test评估发表偏倚,并进行Meta回归、敏感性分析。Meta分析结果提示MCP-1-2518 A/G多态性与癌患病风险无明显相关性。但根据肿瘤类型的亚组分析发现,MCP-1基因多态性与肝癌、乳腺癌、卵巢癌和非小细胞肺癌的发病风险显著相关(p0.05)。根据种族进行的亚组分析发现,携GG基因型的白种人群患癌风险增加(GG vs.AG/AA:OR=1.81,95%CI=1.10~2.96),而MCP-1-2518 A/G多态性与亚洲人群患癌风险无相关性(p0.05)。多态性与癌易感性的关联在基于对照组来源、研究样本量和低质量研究的亚组分析中显著,而根据对照组是否符合HWE遗传平衡和基因检测方法的亚组分析,这种关系不显著。Meta回归分析表明,种族差异和纳入研究的质量可能是各研究间异质性存在的主要来源。综上所述,MCP-1-2518 A/G多态性可能与癌易感性相关,GG基因型可增加白种人群患癌风险,MCP-1基因A2518G位点有望作为癌早期诊断和预后判定的重要分子标志物。     

Pro- and anti-inflammatory cytokines gene polymorphisms and Helicobacter pylori infection: interactions influence outcome

The aim of this study was to evaluate whether there was any correlation between Helicobacter pylori-associated diseases and (1) H. pylori virulence genes or (2) IL-1B, IL-1RN, IFN-G, TNF-A, IL-10 genetic polymorphisms. Patients with non-cardia gastric cancer (NCGC, n=129) or benign gastroduodenal diseases (n=792) were studied. IL-1RN intron 2 VNTR polymorphism (PCR), IL-1B -31 C/T (RFLP), the SNPs of IFN-G (+874 A/T), TNF-A (-1031 C/T, -857 C/T, -376 A/G, -308 A/G, -238 A/G), IL-10 (-1082 A/G, -819 C/T, -592 A/C) (Taqman chemistry) were studied. cagA, s1 and m1 vacA, were PCR amplified. Duodenal ulcer was more frequent in TNF-A -857 TT and in IL-1RN 1,2 subjects. TNF-A -857 TT genotype was also correlated with gastric ulcer. IL-10 -819 TT genotype was associated with intestinal metaplasia and NCGC. Antral inflammation was associated with TNF-A -1031 TT, while corpus activity with IL-10 -819 CC. H. pylori infection was associated with TNF-A -308 AG genotype, while IFN-G +874 AA genotype was associated with cagA. In conclusion, among host genetic factors contributing to H. pylori disease outcome, IFN-G +874 AA genotype favors cagA positive infections, TNF-A -857 TT duodenal ulcer while IL-10 -819 TT intestinal metaplasia and NCGC.     

The Effect of MUC1 rs4072037 Functional Polymorphism on Cancer Susceptibility: Evidence from Published Studies

Genome-wide association studies have identified a susceptibility variation MUC1 rs4072037 for gastric cancer in Chinese population. Subsequent case-control studies have reported this association in other populations. However, the results remain controversial and ambiguous. The aim of this study is to provide a precise quantification for the association between MUC1 rs4072037 variation and the risk of cancer. We performed pooled analysis of 10 case-control designed studies including 4,220 cases and 6,384 controls. Odds ratios (OR) and 95% confidence interval (95%CI) were calculated to assess strength of association in overall studies and in subgroup analysis stratified by ethnicity and cancer types. All statistical analyses were performed by Manager 5.0 and Stata 12.0 software. Overall, the MUC1 rs4072037 polymorphism was associated with risk of cancer in all genetic models (G vs A: OR = 0.71, 95%CI: 0.63–0.80, p<0.01; GA vs AA: OR = 0.61, 95%CI:0.55–0.67, p<0.01; GG vs AA: OR = 0.58, 95%CI: 0.47–0.71, p<0.01; AG+AA vs GG: OR = 0.60, 95%CI: 0.55–0.60, p<0.01; GG vs AG+AA: OR = 0.70, 95%CI: 0.58–0.85, p<0.01). Further, subgroup analysis based on ethnicity suggested MUC1 rs4072037 polymorphism had a subtly reduced cancer risk among Asian population, and stratified analysis by cancer types showed significantly decreased risk of gastric cancer in all genetic models. In conclusion, MUC1 rs4072037 polymorphism may be used as potential biomarker for cancer susceptibility particularly for gastric cancer and for Asian population.     

DNMT3A rs36012910 A>G polymorphism and gastric cancer susceptibility in a Chinese population

DNA-methyltransferase (DNMT)-3A plays a crucial role in embryonic development and aberrant DNA methylation in carcinogenesis. Polymorphisms of the DNMT3A gene may influence its enzymatic activity and its contribution to susceptibility to cancer. This study evaluated the association of DNMT3A rs36012910 A>G with susceptibility to gastric cancer (GC) in a Chinese population. Genomic DNA was extracted from samples taken from 340 patients with GC and 251 healthy control subjects. The genotype frequency of DNMT3A rs36012910 A>G in all subjects was detected by polymerase chain reaction–restriction fragment length polymorphism and confirmed by sequencing. Stratification analyses were used to study subgroups by age and gender and to evaluate the association of rs36012910 A>G polymorphism with genetic susceptibility to GC. All patients and control individuals were successfully genotyped for the DNMT3A rs36012910 A>G polymorphism. The frequency of DNMT3A rs36012910 allele G is 3.39?% in healthy individuals and 7.78?% in GC patients, respectively. The rs36012910 AG genotype was significantly more common in the GC group than in the controls, although the rs36012910 GG genotype was only one case in GC patients. Further stratification indicated that AG+GG genotypes were associated with susceptibility to GC in males older than 60, but this polymorphism has no significant association with GC susceptibility in females. Male individuals who carried AG+GG genotypes had a 2.362-fold increased risk of GC compared to those who carried the AA genotype. The rs36012910 allele G was associated with an increased risk of GC compared to the rs36012910 allele A. This is the first report to investigate the distribution and evaluate the association of a rare SNP in DNMT3A with genetic susceptibility to GC. DNMT3A rs36012910 A>G might become a potential biomarker for use in GC prediction, although further studies in larger groups and different populations are needed for confirmation.     

Meta-analysis of MCP-1 promoter ?2518 A/G polymorphism and SLE susceptibility

The aim of this meta-analysis was to summarize results on the association of monocyte chemoattractant protein-1(MCP-1) promoter -2518 A/G polymorphism with systemic lupus erythematosus (SLE) susceptibility. We searches all the publications about the association between MCP-1 promoter -2518 A/G polymorphism and SLE from Pubmed, Elsevier Science Direct, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure. The meta-analysis was performed for genotypes AA verse GG, AA+AG verse GG, AA verse AG+GG, and A allele verse G allele in a fixed/random effect model. A total of 14 studies (2,333 cases and 2,391 controls) were included in the meta-analysis. When all groups were pooled, we had not observed significant association between A allele and G allele (OR = 0.94, 95 %CI = 0.79-1.12, P = 0.50). When analysis were restricted to more ethnically homogeneous populations, the similar results were found in European population and Asian population (OR = 1.05, 95 %CI = 0.75-1.46, P = 0.80; OR = 1.00, 95 %CI = 0.86-1.17, P = 0.99). However, we had not detected a significant association between MCP-1 promoter -2518 A/G polymorphism and SLE when examining the genotypes AA verse GG, AA+AG verse GG, AA verse AG+GG. The meta-analysis did not demonstrate the association between MCP-1 promoter -2518 A/G polymorphism and SLE.     

Association between a single nucleotide polymorphism in the bovine chemerin gene and carcass traits in Qinchuan cattle

Qinchuan is a red or yellow draft and beef breed in China. In order to identify a predictor of carcass traits on the basis of associations between carcass traits and gene polymorphism, variation in the bovine chemerin gene was investigated using PCR-single-strand conformational polymorphism and DNA sequencing. An SNP of A868G located in exon 2 of the Bos taurus chemerin gene was detected in 716 samples of six breeds (Jiaxian red, Luxi, Nan yang, Qinchuan, Simmental and Luxi crossbred steers, and Xia'nan), all in China, and three genotypes (AA, AG and GG) were found. Based on the χ(2) test, the AA/AG/GG genotype frequencies of all six breeds were found to be in Hardy-Weinberg equilibrium. A possible association of A868G with some carcass traits was investigated in 106 Qinchuan cattle. Animals with the AG genotype were found to have significantly lower mean loin eye area and meat tenderness compared to those with the AA and GG genotypes. However, there was no significant association between any individual haplotype and backfat thickness, water holding capacity or marbling score. We suggest that A868G could be used as a molecular marker in marker-assisted selection for carcass traits.     

Glutathione S-transferase P1 gene polymorphism and bladder cancer susceptibility: an updated analysis

Studies investigating the association between glutathione S-transferase P1 (GSTP1) gene polymorphism and bladder cancer (BC) risk have reported conflicting results. In order to clarify the effect of GSTP1 polymorphism on the BC susceptibility, we conducted an updated system review of published epidemiology studies to provide more precise evidence. We performed a systematic search of PubMed, EMBASE, and China National Knowledge Infrastructure (CNKI). 20 studies with 4,428 BC cases and 5,457 controls were identified. The combined analyses based on all studies showed that there was a significant difference in the genotype distribution in GSTP1(A313G) polymorphism between BC cases and controls not only in Asians (GG vs. AA?+?AG, OR?=?1.59, 95?% CI?=?1.01?C2.51) but also in Caucasians (GG vs. AA?+?AG, OR?=?1.51, 95?% CI?=?1.11?C2.06). Upon stratification for smoking status, we observed no statistically significant difference in genotype distribution of GSTP1 in ever-smokers. Combination of the high-risk genotypes (GSTM1 null?+?GSTT1 null?+?GSTP1 313 A/G or G/G) demonstrated further increase in the BC risk (OR?=?6.64, 95?%CI?=?3.63?C12.16). This meta-analysis suggests that GSTP1 313 G/G polymorphism is a strong predisposing risk factor for BC.