TNF-α 基因多态性与湖南汉族人群类风湿关节炎风险的关系(英文)

目的：研究TNF-α-308基因多态性对湖南汉族人群类风湿关节炎(RA)风险的影响。方法：标本来源于112例 湖南汉族RA患者以及129例健康献血者。TNF-α-308(rs1800629)基因多态性采用限制性片段长度多态性(PCR-RFLP)法 分析。血清TNF-α水平检测采用ELISA方法。结果：湖南汉族人群中RA患者TNF-α-308 A等位基因携带率为3.6%,健康 对照为10.5%(P=0.004);男性RA人群TNF-α-308 A等位基因携带率显著低于男性健康对照(2.8% vs 15.6%,OR=0.179,P= 0.007)。无论男女,同时携带HLA-DRB1*04及TNF-α-308 GG基因型人群RA风险显著增高(OR=6.107),其中女性RA患者 起病更早、血清TNF-α水平更高。结论：湖南汉族人群中,TNF-α-308 G等位基因与RA易感性增高相关,尤其是女性 人群。TNF-α-308 A等位基因可减少男性人群RA风险。     

山东地区汉族人群类风湿关节炎与CD14基因多态性的关联性

目的 探讨山东地区汉族人群CD14基因rs2569190和rs2563298多态性与类风湿关节炎(RA)易感性的关联性.方法 采用高分辨率熔解曲线方法对256例RA患者及331例健康对照者进行基因分型,计算各位点基因型及等位基因频率,检测血沉(ESR)、C反应蛋白(CRP)、抗环瓜氨酸多肽抗体(CCP)、葡萄糖6磷酸异构酶(GPI)等指标,比较两组各位点之间基因型及等位基因频率分布差异.结果 CD14基因rs2569190等位基因频率在RA组和对照组间差异有统计学意义(P=0.017),基因型分布在两组间差异无统计学意义(P=0.058);rs2563298基因型及等位基因频率在两组间差异无统计学意义(P =0.444,0.599).经Bonferroni多重检验校正后,rs2569190等位基因频率在RA组与对照组间差异有统计学意义(校正后P=0.034).CD14基因rs2569190和rs2563298在年龄、性别、病程、DAS28及各项指标上不同基因型间差异无统计学意义(P＞0.05).结论 在山东地区汉族人群中CD14基因rs2569190多态性与类风湿关节炎易感性可能有关联.     

血清淀粉样蛋白A1基因多态性与类风湿关节炎淀粉样变性的关系

目的探讨血清淀粉样蛋白A1(SAA1)基因多态性及与类风湿性关节炎(RA)淀粉样变性的关系。方法利用聚合酶链反应—限制性片段长度多态性分析和腹部脂肪活检,对152例健康人和159例RA患者的SAA1进行分析。结果2组均发现1.1、1.3和1.5共3种等位基因和1.1/1.1、1.1/1.5、1.1/1.3、1.3/1.3、1.3/1.5及1.5/1.5共6种基因型,RA淀粉样变性组1.3等位基因频率显著高于对照组(P<0.001)。结论SAA1的等位基因1.3可能与RA淀粉样变性有一定的关系,SAA1.3基因型的RA患者定期作腹部脂肪活检对早期发现淀粉样变性有重要意义。     

宁夏回族人群HLA-DQB1基因多态性与类风湿性关节炎的相关性

目的:探讨宁夏回族人群HLA-DQB1基因多态性与类风湿性关节炎(RA)的相关性。方法:采用序列特异性引物聚合酶链式反应(SSP-PCR)的方法对宁夏回族66例健康个体及70例RA患者的HLA-DQB1位点进行基因分型,应用遗传学统计方法对DQB1基因多态性与RA的相关性进行分析。结果:对照组与病例组等位基因的构成及基因型分布具有统计学意义。在对照组中,0501/0501和0501/0601这2种基因型频率最高,均为10.61%,在病例组中,0301/0303基因型频率最高(17.14%),0301/0302基因型频率次之(10.00%);*0501等位基因频率在对照组中高达24.24%,而在患者中仅为5%;*0301等位基因在RA患者中频率高达28.57%,而在对照组中仅为3.79%。结论:0301/0303和0301/0302这2种基因型可能与宁夏回族RA的易患性有关,*0301等位基因可能是宁夏回族易患RA的危险因子,而*0501等位基因可能为宁夏回族抗RA的基因。     

TAP基因多态性与维吾尔族人群类风湿关节炎的相关性

目的研究抗原处理相关转运体(TAP)在新疆维吾尔族人群基因多态性及其与类风湿关节炎(RA)的相关性。方法采用ASPCR方法对64例RA患者和72例正常人的TAP基因进行分析。结果健康维吾尔族人群TAP1 333位和637位等位基因基因型分别以I和D为主,表现型主要为II和DD,TAP2 379、565、665、687等位基因基因型分别以I-A-T-S为主,表现型以II-AA-AT-SS为主;RA患者TAP2 379-V,687-Q,687-QQ频率显著降低,687-S,379-II,687-SS频率显著升高。结论维吾尔族健康人群及RA患者TAP基因多态性有不同于其他民族人群的基本特点。TAP2 379-II、687-SS型患RA的相对危险性增加,并可能是维吾尔患者RA的易感基因。     

HLA—G基因14bp插入／缺失多态性与我国汉族类风湿关节炎相关性研究HLA—G基因14bp插入／缺失多态性与我国汉族类风湿关节炎相关性研究

目的探讨HLA—G基因14bp插入／缺失多态性与类风湿关节炎（RA）易感性的相关性,并分析其不同基因型间RA患者临床特点的差异。方法多聚酶链式反应（PCR）检测154例RA患者及367名健康体检者的HLA—G基因14bp插入／缺失多态性,比较不同基因型RA患者间关节肿胀数、关节压痛数、关节晨僵时间、病情活动指数DAS28积分及实验室指标如C反应蛋白（CRP）、血沉（ESR）、类风湿因子（RF）、抗CCP抗体滴度的差异。结果HLA-G 14bp插入／缺失多态性基因型频率分布在正常人和RA患者均显示Hardy-Weinberg平衡（正常人组：χ^2=0．095,P=0．953;RA组：χ^2=0．533,P=0．766）;HLA—G1 4bp插入／缺失多态性基因和基因型频率与RA易感性均元显著性的相关性联系;与＋14bp／＋14bp和＋14bp／-14bp基因型RA患者比较,-14bp／-14bp纯合子基因型RA患者的压痛关节数（P=0．049）、肿胀关节数（P=0．004）明显增多,病情活动指数DAS28明显更重（P=0．028）,RF滴度更高（P=0．001）。结论HLA-G基因14bp插入／缺失多态性与RA疾病易感性无关,但可影响RA患者的临床表现,HLA-G—14／-14bp纯合子型可能作为预后不良因素参与到RA疾病机制之中。     

非HLA类遗传易患基因多态性与类风湿关节炎的相关研究进展

类风湿关节炎(RA)的发病机制可能与遗传、环境、感染、性激素等因素有关。近年来关于RA的遗传学研究越来越受到关注,大量RA相关的基因多态性研究被报道。人类白细胞抗原(HLA)基因多态性与RA的发病及严重程度密切相关,为RA的早期诊断、严重程度评估以及预后判断提供了新的思路。此外,多种非HLA类基因多态性在RA的发生、发展中也起到重要作用。     

CYP1B1基因多态性与子宫内膜癌易感性的关系

目的研究CYP1B1基因外显子3密码子432（C-G）多态性与子宫内膜癌易感性的关系。方法应用聚合酶链反应-限制性片断长度多态性分析（PCR-RFLP）技术检测76例子宫内膜癌患者和83例对照者的CYP1B1基因密码子432（C-G）位点多态性,并分析CYP1B1基因多态性与子宫内膜癌易感性的相关性。结果CYP1B1基因密码子432中等位基因C、G在子宫内膜癌组和对照组分布的差异有统计学意义（P〈0.05）,其中等位基因G使子宫内膜癌发病风险增加2.24倍。CYP1B1基因密码子432C/G各基因型分布两组间差异有统计学意义（P〈0.05）,纯合突变（G/G）基因型、杂合突变（C/G）基因型与野生（C/C）基因型相比,患子宫内膜癌的危险度分别提高了5.62倍和2.04倍。结论CYP1B1基因Leu432Val多态性与子宫内膜癌的发生有一定的关系,突变基因型增加子宫内膜癌的发病风险。     

广东汉族人群类风湿性关节炎患者TGF-β1与IL-1β基因多态性的研究

目的 探讨广东地区汉族人群TGF-β1（+915G/C）以及IL-1β（-31 C/T）基因多态性及其与RA相关性。方法 分别采用PCR-SSP技术（TGF-β1+915G/C的检测）和PCR-RFLP技术（IL-1β-31C/T的检测）检测120名健康体检者和111例RA患者基因型。结果 TGF-β1（+915）有GG、GC、CC三种基因型,健康体检者与RA患者间的基因型未有统计学意义（χ2 =0.05,P =0.975）;IL-1β（-31）有CT、CC和TT三种基因型,健康体检者和RA患者间的基因型有统计学意义（χ2 =8.86,P =0.012）,且RA患者的C等位基因频率明显高于健康对照组（χ2=6.34,P =0.012,OR=1.64,95%CI：1.11～2.41）;在RA患者组中,活动期患者的C等位基因频率亦明显高于缓解期的C等位基因频率（χ2=28.63,P =0.000,OR=6.87,95%CI：2.40～20.27）。结论 TGF-β1（+915）基因多态性与RA无相关性;IL-1β（-31）基因多态性与RA具有相关性,且C等位基因可能是RA疾病的易感基因,CC基因型的人患RA疾病的概率较高。     

类风湿关节炎患者的HLA—DM基因多态性分析

目的：探讨我国汉族类风湿关节炎（RA）患者的HLA－DM（DMA和DMB）基因的多态性及与临床的相关性。方法：应用多聚酶链反应。序列特异性寡核苷酸探针（PCR／SSOP）检测96例RA患者及100名正常人HLA－DM基因第三外显子多态性，并应用PCR／限制性片段长度多态性分析（PCR／RFLP）筛选HLA-DRB*0405阳性个体。结果：类风湿关节炎患者和正常人群的DM等位基因均以DMA＊0101和DMB＊0101为主（分别为86．5％和87．5％，及85．0％和90．0％）。DM等各位基因表型频率在RA组和正常对照组之间均无显著性差异。HLA－DRB1＊0405阳性的RA组与正常对照组也无显著性差异。DRB1＊0405阳性率、RF滴度在DMB＊0101组显著高于DMB＊0102组（P值分别小于0．01和0．05）。结论：DM基因多态性可能不影响RA的易感性，但在一定程度上可能对RA病情及活动性有重要影响。     

IL-6和IL-18基因启动子多态性与广东汉族人群类风湿性关节炎相关性研究

目的 了解我国广东地区汉族人群白细胞介素-6(IL-6)和白细胞介素-18(IL-18)基因启动子单核苷酸多态性及与类风湿性关节炎(RA)的相关性.方法 应用序列特异性引物-聚合酶链反应(PCR-SSP)技术检测168名健康体检者和120例RA患者的IL-6基因启动子-572和-174及IL-18基因启动子-607C/A和-137G/C单核苷酸多态性.结果 对照组和患者组IL-6基因启动子-572位点、-174位点和IL-18基因启动子-607C/A位点、-137G/C位点均存在单核苷酸多态性.IL-6-572位点、-174位点和IL-18-607位点基因型和等位基因频率分布在RA组和对照组间差异均有显著性(P＜0.001).IL-18-137位点基因型频率在两组间无统计学意义(P=0.141),但等位基因分布频率在两组间差异有显著性(P=0.024).经Logistic回归分析,年龄、性别、IL-6-572位点、-174位点和IL-18-137位点与RA有相关性(P＜0.05).结论 广东汉族人群IL-6基因启动子-572和-174单核苷酸多态性与RA可能相关,IL-18基因启动子-607C/A和-137G/C单核苷酸多态性与RA是否相关需进一步研究.     

Interleukin- 1 gene polymorphism disease activity and bone mineral metabolism in rheumatoid arthritis

Objective To determine whether interleukin- 1α and 1β gene polymorphism is associated w ith rheumatoid arthritis disease activity and bone mineral metabolism, and whet her there is any relationship between IL- 1β and rheumatoid arthritis (RA) moti f gene. Methods IL- 1 gene polymorphisms were analyzed in 65 RA patients who met American College of Radiology (ACR) criteria and 60 controls. From genomic DNA, 2 polymo rphisms in each gene for IL1α- 889 and IL- 1β+3953 were typed by PCR- RFLP and HLA- DRB1 allele typing was also undertaken by PCR- SSOP. Some clinical and l aboratory parameters were collected. The allelic frequencies and carriage rate s were compared between RA patients and controls and between patients with acti ve and quiescent disease. Comparison was also made between IL- 1 polymorphism a nd parameters of bone mineral metabolism and between patients with the HLA- DRB1 RA motif plus IL- 1β2 and patients without the two alleles. Fisher test an d the analysis of variance was used to analyze the data. Results There was no significant difference in the frequency and carriage rate of IL- 1 α polymorphisms between RA patients and the controls. The β2/2 genotype of IL - 1β was more common in female RA patients compared with controls (P=0. 001 ). A lower carriage rate of IL- 1β2 occurred in male RA patients (P=0. 0 01). A higher carriage rate of IL- 1α2 is associated with a higher ESR (P =0. 008), HAQ score (P=0. 03), and vit- D(3) (P&lt;0. 001), but conversely a lower SJC (p=0. 002), a lower RF (P=0. 002) and a lower BMD at the l um bar spine (P=0. 001). A higher frequency of IL- 1α1 is associated with a l ow er CRP value (P=0. 009). An increased IL- 1β2 carriage is associated with active rheumatoid disease as indicated by a higher CRP (P&lt;0. 001), ESR ( P&lt;0. 001) and pain score (P=0. 001) and a higher BMD at the lumbar spin e (P=0. 007), lower vit- D(3) and. Udpd/Crea level The presence of the HLA DR B1 RA motif and IL- 1β allele 2 at same time did not contribute to disease acti vity. Conclution Polymorphisms of the IL- β gene may affect the RA occurrence. Carriage of IL- 1β2 polymorphisms is associated with more active disease in RA and the presenc e of both the IL- 1α2 and the IL- 1β1 allele in RA influences bone resorption .     

Association between the eNOS gene polymorphisms and rheumatoid arthritis risk in a northern Chinese population

Background Several genetic polymorphisms in the endothelial nitric oxide synthase (eNOS) gene are associated with the pathogenesis of rheumatoid arthritis (RA). The objective of the present study was to investigate whether the two SNPs (T-786C and G894T) of the eNOS gene are associated with rheumatoid arthritis risk in a northern Chinese population.

Methods  In this study, the eNOS genes T-786C and G894T were studied in 196 cases with rheumatoid arthritis and 201 healthy controls with gender, age and ethnicity matched. The two SNPs were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The analyses of association were statistically compared using the chi-square test with SPSS software for Windows.

Results  The frequency of the -786C allele was significantly higher in the rheumatoid arthritis patients than in the healthy controls (19.64% vs. 14.18%, P <0.05). However, the 894T allele of the eNOS gene was not increased in the rheumatoid arthritis patients compared to the healthy controls.

Conclusions  Individuals with the -786CC genotype have an increased risk of rheumatoid arthritis. Further study with an increased sample size is necessary for the study of the role of this SNP in rheumatoid arthritis.

     

Association of NFATc1 gene polymorphism with ventricular septal defect in the Chinese Han population

Background Congenital heart disease (CHD) is a diverse group of diseases determined by genetic and environmental factors.Considerable research has been done on genes associated with the development of ...     

SLC1A1基因多态性与中国汉族人群强迫症的相关性

目的：探讨谷氨酸转运体基因（SLC1A1）与中国汉族人群强迫症（OCD）的关系。方法：采用病例对照研究,以125例患者（OCD组）和125例正常人（对照组）作为研究对象,检测SLC1A1基因的3个位点（rs301430、rs301434、rs301979）,分析这些位点等位基因、基因型分布,以及单倍体与OCD之间的关系。结果：3个位点的等位基因和基因型频率分布在OCD组和对照组中的差异无统计学意义（P＞0.05）。经性别分层分析,相较于对照组,女性患者rs301979位点等位基因和基因型频率分布与对照组差异有统计学意义（χ2=7.875,P=0.019;χ2=7.331,P=0.007）,而男性患者中所有位点的等位基因和基因型频率分布差异均无统计学意义（P＞0.05）。三位点单倍体T-A-G在2组中的差异有统计学意义（χ2=6.206,P=0.013）。结论：SLC1A1基因rs301979位点可能是女性OCD的易感基因位点,rs301430、rs301434、rs301979的单倍体T-A-G可能与中国汉族人群OCD发病相关。     

ADAMTS-1基因多态性与汉族人群原发性高血压相关性研究

目的探讨汉族人群原发性高血压与含血小板反应素的去解联金属蛋白酶1（ADAMTS-1）基因启动子区rs402007（G/C）位点多态性的关联。方法提取汉族469例原发性高血压患者和229例血压正常的健康体检者（正常对照组）外周血液中的基因组DNA。采用多聚酶链反应和基因测序法对包含rs402007多态性位点在内的ADAMTS-1基因-99/+447目的片段进行基因检测,并进行Hardy-Weinberg平衡检验,检测研究群体有无群体代表性。结果原发性高血压组rs402007位点GC+CC基因型频率、C等位基因频率均高于正常对照组,差异均有统计学意义（均P＜0.05）。校正危险因素后,两组间GC+CC基因型频率差异仍有统计学意义（P=0.028,OR=1.809,95%CI：1.067~3.067）。结论ADAMTS-1基因rs402007位点多态性与汉族人群原发性高血压患病相关,C等位基因可能是原发性高血压的易感等位基因。     

Rs548234 polymorphism at PRDM1-ATG5 region susceptible to rheumatoid arthritis in Caucasians is not associated with rheumatoid arthritis in Chinese Han population

Background  A previous study has shown that rs548234 polymorphism at PRDM1-ATG5 region is associated with rheumatoid arthritis (RA) in Caucasian populations. The aim of this study was to investigate the effect of rs548234 polymorphism at PRDM1-ATG5 region on susceptibility to RA in Chinese Han population.

Methods  We genotyped 848 RA patients and 1431 matched healthy controls for rs548234 single-nucleotide polymorphism (SNP) with a predesigned TaqMan SNP genotyping assay. Association analyses were performed on the whole data set and on rheumatoid factors (RF) and anti-cyclic citrullinated peptides (anti-CCP) antibody. Finally, we carried out combined analysis of rs548234 association with RA based on the published data.

Results  No significant difference in the genotype distribution between RA patients and healthy controls for rs548234 (C/T) polymorphism was found in Chinese Han population, neither in whole data set nor in stratified subsets, e.g. RF and anti-CCP status. Association analysis in different ethnic groups showed that rs548234 at PRDM1-ATG5 region was associated with RA in Caucasian ancestry but not in East Asian population.

Conclusions  Our results showed no involvement of rs548234 at PRDM1-ATG5 region in the susceptibility or clinical relevance of RA in Chinese Han population.

     

人鱼精蛋白1多态性与汉族男性生育力的相关性分析

目的  研究人类鱼精蛋白1（PRM1）C321A多态性与汉族男性生育力的相关性。方法  选取174例原发不育男性患者为观察组,172例生育男性为对照组,分别分析两组常规精液参数,采用限制性酶切及DNA测序技术对PRM1 C321A位点进行基因分型。结果  不育患者PRM1 C321A位点AA基因型频率（8.05%）显著高于生育男性（2.33%）（P <0.01）,分析显示AA基因型与男性不育的遗传易感性明显相关[■=4.24（95%CI：1.33,13.51）]。AA基因型可使精子前向运动能力及正常形态比例等参数明显下降,可能是其导致男性不育的主要因素。结论  PRM1 C321A多态性改变与汉族男性生育力相关。