IRF5基因多态性与山东汉族人群系统性红斑狼疮的相关性研究

目的 研究山东地区汉族人群干扰素调节因子5(IRF5)基因rs2004640、rs10954213单核苷酸多态性,探讨其与系统性红斑狼疮(SLE)易感性之间的关系.方法 采用聚合酶链反应和限制性片段长度多态性等方法对92例SLE患者和88名健康对照IRF5基因rs2004640 G/T、rs10954213 G/A多态性进行分析,计算基因型和等位基因频率.结果 SLE患者IRF5 rs2004640GG、GT、TT基因型频率分别是0.198、0.521和0.281,与对照组比较差异有统计学意义(X2=8.73,P<0.05);SLE患者IRF5 rs10954213 GG、GA、从基因型频率分别是0.318、0.409和0.273,与对照组间差异有统计学意义(X2=6.36,P<0.05).结论 山东汉族人群IRF5基因位点rs2004640、rs10954213的多态性,可能与山东地区汉族人群SLE的易感性有关,需进一步累积更多数据证实.     

ETS1基因与中国北方汉族人群系统性红斑狼疮的相关性研究

目的 验证ETS1基因在北方汉族人群系统性红斑狼疮(systemic lupus erythematosus,SLE)发生中的作用.方法 应用病例-对照关联研究,在山东汉族人群中收集231例SLE患者和474名正常对照,采用Taqman探针对ETS1基因3’非翻译区区域单核苷酸多态位点rs1128334与rs4937333进行基因分型,并对数据进行统计学计算和单倍型分析.结果 rs1128334等位基因A在病例组中的频率显著高于对照组(42.8％ vs.29.1％,OR=1.824,95％CI:1.445～2.302,P＜0.01),rs4937333等位基因T在病例组中的频率显著高于对照组,差异具有统计学意义(47.6％ vs.38.1％,OR=1.478,95％CI:1.181～1.851,P＜0.01).两位点的单倍型分析显示单倍型A-T与SLE的发病风险显著相关(P＜0.05,OR=0.738,95％CI:0.564～0.964),而单倍型G-C可以显著降低SLE的发病风险(P＜0.01,OR=0.296,95％CI:0.232～0.378).结论 ETS1基因rs1128334和rs4937333位点与北方汉族人群系统性红斑狼疮相关.     

中国汉族人群FcγRIIIA F158V基因多态性与系统性红斑狼疮及狼疮肾炎相关

目的研究中国汉族人群中,FcγRIIIA F158V单核苷酸多态性(SNPs)的分布,以及对系统性红斑狼疮(SLE)特别是狼疮肾炎(LN)的遗传易感性和病程变化等的影响。方法采用病例-对照研究,收集在北京协和医院就诊的324例SLE患者和相匹配的非自身免疫性疾病的319名健康志愿者和体检对照,利用多聚酶链式反应(PCR)、限制性片段长度多态性(RELP)以及DNA测序验证等技术检测FcγRIIIA F158V基因型。进一步结合临床资料进行统计分析。结果在中国汉族人群中,FcγRIIIA基因的F等位基因频率约为60.8%。FcγRIIIA基因多态性在SLE组和对照组之间存在显著差异,FF基因型的SLE患者出现LN的风险较高,而VV基因型的SLE患者出现早发LN的风险较低。结论 FcγRIIIA基因多态性与SLE的发病有关,FF纯合子基因型可能存在对LN的易感性。VV纯合子基因型可能对LN晚发存在一定保护作用。     

贵州汉族TGF-β1基因多态性与系统性红斑狼疮相关性的研究

目的：探讨转化生长因子-β1（TGF-β1）基因启动子-509C/T多态性与贵州汉族人群系统性红斑狼疮（SLE）的相关性。方法：采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）技术，分析80例SLE患者及95例正常对照组的TGF-β1基因启动子-509C/T多态性。结果：SLE组与正常对照组-507C/T基因型频率分布有差异（P〈0.05），-509CC基因型SLE组高于对照组（35% vs 21.1%），而-509TT型SLE组明显低于正常对照组（18.75% vs 36.8%）；SLE患者组-509位点的等位基因频率与正常对照组比较差异也有显著性（P〈0.005），SLE组C等位基因频率显著高于对照组（58.1% vs 42.1%），T等位基因频率低于对照组（41.9% vs 57.9%）。结论：贵州汉族人群TGF-β1基因启动子-509C/T多态性与SLE显著相关。     

系统性红斑狼疮易感基因单核苷酸多态性研究进展

系统性红斑狼疮(systemic lupus erythematosus,SLE)是一种复杂的多基因自身免疫性疾病,遗传因素重要而复杂.SLE的易感基因包括人类白细胞抗原(HLA)基因、免疫球蛋白Fc受体(FcR)基因、细胞毒性T细胞相关抗原4(CTLA-4)基因、免疫球蛋白受体同源体(FcRL)基因等.对易感基因单核...     

中国人群系统性红斑狼疮患者OAZ基因多态性研究

目的　研究 OL F1/EBF相关锌指蛋白 (OL F1/EBF associated zinc finger protein,OAZ)基因单核苷酸多态性 (single nucleotide polymorphism,SNP)与系统性红斑狼疮 (systemic lupus erythematosus,SL E)的关联性。方法　选择经过验证、杂合度较高的 SNP对 2 4 4个 SL E家系进行等位基因分型 ,以Genehunter软件分析单个位点及单倍型传递情况。检测 OAZ基因表达水平 ,比较患者中不同单倍型对基因表达的影响。结果　未发现单个 OAZ SNP位点在 SL E患病子代中优势传递。单倍型分析显示 ,由rs1344 5 31- rs2 0 80 35 3- rs9335 6 4 - rs1345 4 31构成的单倍型 T- A- G- G与疾病连锁性较弱 (P=0 .0 4 ) ,而Rs9335 6 4 - D16 s5 17构成的单倍型 G- 2 71bp、Rs2 0 80 35 3- rs9335 6 4 - D16 s5 17构成的单倍型 A- G- 2 71bp优势传递给患者 (P=0 .0 0 0 0 0 0和 0 .0 0 0 0 0 2 )。 Rs2 0 80 35 3- rs9335 6 4 - D16 s5 17- rs1345 4 31构成的单倍型 A- G-2 71bp- G也优势传递给患者 (P=0 .0 0 84 ) ,且该单倍型与基因表达水平相关。结论　 SL E患者中存在特定的 OAZ基因单倍型 ,OAZ可能提示了狼疮发病的新通路。     

中国南方汉族人群HLA—DQA1位点多态性与系统性红斑狼疮易感…

应用多聚酶链反应／序列特异寡核苷酸探针杂交（ＰＣＲ／ＳＳＯＰＨ）方法，探讨了我国东南沿海汉族人群ＨＬＡ－ＤＱＡ１等位基因多态性与系统性红斑狼疮（ＳＬＥ）的易感性关系，对５０例ＳＬＥ患者和６７例健康人对照血样本分析，表明ＳＬＥ患者具有显著高的ＤＱＡ１＊０１０２等位基因频率，ＯＲ＝４６．０４，Ｐ＜０．００１，可能是一易感等位基因，而ＤＱＡ１＊０５０１在病例与对照中呈相反结果，ＯＲ＝０．０４２，Ｐ＝０。     

华南、华北人群HLA-DQB1等位基因多态性

目的从基因水平调查了中国华南、华北地区人群HLA-DQB1等位基因频率，并研究比较两地区人群HLA-DQB1多态性分布。方法采用深圳益生堂生物企业有限公司研制开发的“HLA-DQB1低分辨率分型基因芯片检测试剂盒”，应用聚合酶链反应．序列特异性引物＋序列特异性寡核苷酸探针芯片检测技术，对700名南方地区的中国人和320名北方地区的中国人进行基因分型。结果鉴定了10个HLA-DQB1等位基因，获得了一组准确、科学的统计数据。结论得到了中国华南、华北地区人群HLA-DQB1等位基因频率差异的数据，证明中国人群HLA-DQB1＊02，05，0601，0602，0603的分布南北差异有统计学意义（P〈0．05），为疾病相关性研究、人文科学研究提供了可靠的遗传学数据。     

HSP90B1基因多态性与系统性红斑狼疮易感性的关联研究

目的：探讨HSP90B1基因多态性与中国汉族人群系统性红斑狼疮(SLE)易感性的关系。方法：从医院收集360例对照和360例SLE患者,按照年龄和性别进行匹配。利用Multiplex SNaPshot分型技术对SNP位点分型。采用基于错误发现率 (FDR) 标准的本杰明-汉伯格 (BH) 法进行多重检验校正。结果：显性模型分析发现rs1165681的基因型频率分布在对照组和SLE组之间存在统计学差异(Crude OR = 0.621, 95%CI = 0.450-0.856, P=0.004; Adjusted OR = 0.619, 95%CI = 0.449-0.855, P=0.004);隐性模型分析发现rs10778306 (Crude OR = 0.568, 95%CI = 0.328-0.984,P = 0.044; Adjusted OR = 0.570, 95%CI = 0.329-0.988, P = 0.045)、rs2722188(Crude OR = 0.227, 95%CI = 0.076-0.681, P = 0.008; Adjusted OR = 0.227, 95%CI=0.076-0.682, P=0.008) 的基因型分布在两组之间存在统计学差异。BH法校正后,rs1165681基因型分布在两组之间有统计学差异 (P_BH = 0.044)。单倍型分析后CCATTAGGCAT(OR=0.323, 95%CI=0.154-0.680, P = 0.002)、CCCTTAGGCAC (OR = 1.324, 95%CI = 1.014-1.729, P =0.039)、TCCCTAGTCGC(OR = 0.465, 95%CI = 0.221-0.979, P = 0.039)和TTCTCGGGCAT(OR=0.443, 95%CI = 0.224-0.875, P = 0.016) 与SLE的发病风险有关;BH法校正后,CCATTAGGCAT在两组之间的分布有统计学差异(P_BH = 0.028),其他单倍型均无统计学差异 (P>0.05)。结论：HP90B1基因多态性可能与中国汉族人群的SLE发病有关。     

广西人群S100B基因多态性与系统性红斑狼疮的相关性研究

目的:探讨S100B基因rs9984765、rs2839356和rs2186358遗传多态性与系统性红斑狼疮(SLE)的相关性。方法:选取313例SLE患者作为病例组,年龄和性别匹配的396例正常人作为对照组,采用单碱基延伸PCR技术(SBE-PCR)和DNA测序法对S100B基因3个位点进行基因分型检测。结果:rs9984765和rs2186358位点的基因型和等位基因频率在SLE患者组和对照组间分布差异均无统计学显著性,而rs2839356位点的C等位基因在两组间比较差异有统计学意义(P=0. 040)。进一步分析rs2839356位点的等位基因与SLE患者临床表现的关系,发现rs2839356位点的C等位基因在伴有神经系统病变的SLE患者中高于不伴有神经系统病变的SLE患者(P=0. 023)。结论:在广西人群中,S100B基因rs9984765和rs2186358位点的基因多态性可能与SLE的遗传易感性无关,而携带rs2839356的C等位基因可能具有增加SLE及其并发神经系统病变的发病风险。     

BARD1单核苷酸多态性与汉族儿童神经母细胞瘤相关性的研究

目的 探讨BARD1单核苷酸多态性与汉族儿童神经母细胞瘤的相关性.方法 采用病例对照研究,收集242例汉族神经母细胞瘤患儿及301例汉族健康儿童的外周血,通过PCR方法扩增目的DNA,应用Sequenom massarray对所扩增的DNA进行基因分型.以x2检验及logistics分析比较不同组基因型与神经母细胞瘤的关系.结果 BARD1的21个标签SNPs位点均符合Hardy-Weinberg平衡,BARD1的21个SNPs等位基因频率在患者组与对照组之间差异均无统计学意义(P＞0.05).结论 未发现BARD1单核苷酸多态性与汉族儿童神经母细胞瘤有相关性.     

Association between IL-33 Gene Polymorphisms (rs1929992, rs7044343) and Systemic Lupus Erythematosus in a Chinese Han Population

Objective: Interleukin-33 (IL-33) is a member of the IL-1 family, and previous studies found the single-nucleotide polymorphisms (SNPs) in the IL-33 gene was related to susceptibility to autoimmune diseases, including rheumatoid arthritis, ankylosing spondylitis and Behcet’s disease. To date, no study has discussed the potential association between IL-33 gene polymorphisms and systemic lupus erythematosus (SLE).

Methods: We conducted a case-control study including 371 SLE patients and 408 healthy controls to investigate the correlation between the SNPs of IL-33 gene (rs1929992, rs7044343) and SLE in a Chinese Han population.

Results: There was significantly lower expression of allele G for rs1929992 in SLE patients than that in controls (G versus A, P = 0.012, OR = 1.310, 95% CI: 1.060–1.624 after adjustment with sex). Similarly, genotype GG was associated with the susceptibility to SLE as compared with the AA genotype (P = 0.017, OR = 1.714, 95% CI: 1.101–2.669 after adjustment with sex). We also found statistical significance in the dominant model (GG+GA versus AA, P = 0.017, OR = 1.481, 95% CI: 1.074–2.044 after adjustment with sex). However, we found no strong evidence for the association of IL-33 rs7044343 polymorphism with SLE. Moreover, association studies were performed on the relationship between the IL-33 gene polymorphisms and lupus nephritis as well as nine clinical features of SLE, but there was no significant association regarding the distribution of allele and genotype frequencies between SLE patients positive and negative for the presence of sub-phenotypes.

Conclusion: Our findings indicate that IL-33 rs1929992 polymorphism may be a potential biomarker for susceptibility to SLE.     

Programmed Death-1 Gene Polymorphisms in Patients With Systemic Lupus Erythematosus in Taiwan

To investigate the role of programmed cell death-1 (PD-1) gene polymorphisms in the development of systemic lupus erythematosus (SLE) in Taiwan, 109 patients with SLE and 100 healthy controls were enrolled in this study. The PD-1 gene polymorphisms were determined by the method of polymerase chain reaction/restriction fragment length polymorphism. This study showed that the genotype distributions of PD-1 7209 C/T polymorphisms were significantly different between the patients with SLE and controls (P=0.002, Pc=0.018). The frequencies of the PD-1 7209 C/C genotype and PD-1 7209 C allele were significantly higher in the patients with SLE than those of the controls (P=0.001, OR=2.6, 95% CI=1.5–4.6, and P=0.002, OR=2.1, 95% CI=1.3–3.4, Pc=0.018, respectively). Moreover, the association of PD-1 7209 C with susceptibility to SLE was independent of the PD-1 ligand. This study also showed that the PD-1-536 A 7146 G 7209 C 7499 G haplotype was associated with the development of SLE in Taiwan.Both Authors Contributed equally to this work     

CD11b单核苷酸多态性与中国汉族系统性红斑狼疮的研究

目的 分析CD11b基因rs1143679的单核苷酸多态性(SNP)在中国汉族系统性红斑狼疮(SLE)患者中的表达,并阐明该SNP与SLE临床表型的相关性.方法 采用病例对照的研究方法,应用PCR-PFLP以及直接测序技术对中国汉族人群中584例系统性红斑狼疮患者和624例健康对照者进行多态性检测,分析基因型和等位基因频率的分布差异,并与临床表型进行相关性分析.结果 (1)SLE患者中CD11b rs1143679 GA基因型频率为1.89％,大大低于欧美国家的基因型频率,与香港及泰国地区接近.(2) CD11b rs1143679 GA基因型与狼疮肾炎有相关性(P=0.01),而与发病时间、关节炎、血液系统、神经系统损害没有统计学差异(P＞0.05).结论 CD11b rs1143679 SNP与中国汉族人群系统性红斑狼疮易感性有关,并可能参与了狼疮肾炎的发生发展.     

Genetic Polymorphism (rs329498) in the Pellino-1 Gene as Possible Predisposal Factor for Systemic Lupus Erythematosus in a Chinese Population

Objective: The purpose of this study was to analyze the association of two single nucleotide polymorphisms (SNPs) in Peli-1 gene with systemic lupus erythematosus (SLE) in a Chinese population.

Methods: We conducted a case–control study and a total of 738 SLE patients and 827 healthy controls were finally recruited. Peli-1 rs329498 and rs10496105 polymorphisms were specified from genomic DNA using TaqMan genotyping assay on Fluidigm 192.24 system.

Results: Allele contrast showed the minor allele C was associated with decreased risk for SLE when compared with the A allele (OR = 0.851, 95% CI = 0.737–0.983, p = 0.028). Significant difference was observed in genotype distribution of rs329498 polymorphism between lupus nephritis (LN) patients and non-LN patients (χ² = 8.18, p = 0.017). Furthermore, we also found a decreased frequency of the minor allele C in LN patients (29.2%) than in non-LN patients (37.7%) (χ² = 8.67, p = 0.003). Moreover, a significant difference was also detected under a dominant model with regard to the distribution of genotype frequencies between LN patients and non-LN patients (CC + AC vs. AA: OR = 0.632, 95% CI = 0.451–0.884, p = 0.007). Clinical features analysis showed a significant difference in the distribution of genotypic frequencies between patients with malar rash and patients without this feature (χ² = 6.63, p = 0.036). Unfortunately, we failed to find any significant results between Peli-1 gene rs10496105 and SLE susceptibility.

Conclusions: Our observations suggested that Peli-1 gene polymorphism rs329498 might contribute to SLE susceptibility in Chinese Han Population. Likewise, the rs329498 SNP was also associated with the clinical features LN and malar rash in SLE patients.     

Common Polymorphisms in the CACNA1H Gene Associated with Childhood Absence Epilepsy in Chinese Han Population

Variants with a relatively high frequency in the CACNA1H gene have previously been identified in cases of childhood absence epilepsy (CAE) in the Chinese Han population most of which are located in exons 6 to 12. In present study we attempted to further investigate whether the CACNA1H gene is associated with CAE. Exons 6 to 12 of CACNA1H gene were sequenced in samples of 100 CAE trios recruited consecutively, and 191 normal human controls. Single nucleotide polymorphisms (SNPs) were studied in both single locus and haplotype analyses in 218 CAE trios, of which 118 trios were selected from our previous research. Case-control comparisons and the transmission disequilibrium test (TDT) both supported a coding SNP (cSNP) rs9934839 (R603R) in exon 9 as being close related to CAE. The carriers of the G allele of rs9934839 had a 3-fold higher risk of CAE than non-carriers. Moreover, another cSNP rs8044363 was predicted to be connected directly with CAE in a Bayesian network. In addition, two haplotypes consisting of five cSNPs in the region of CACNA1H were statistically associated with CAE. Our research provides new evidence to further support the hypothesis that CACNA1H may be an important susceptibility gene for CAE in the Chinese Han population.     

中国大陆汉族人群强直性脊柱炎患者骨保护素基因多态性研究

目的：通过骨保护素（OPG）基因单核苷酸多态性（SNPs）位点的筛查,分析中国大陆汉族人群中OPG基因多态性与强直性脊柱炎（AS）易感性的相关性。方法：采集2008年1月至2012年1月在我院就诊的AS患者195例（AS组）及203例性别、年龄与之匹配的健康体检者（对照组）的外周血样本,并提取基因组DNA。所有样本采用TaqMan探针法对OPG基因SNP rs2073618、rs4355801位点进行基因型鉴定。比较AS组与对照组之间不同等位基因及基因型的分布差异,并分析其与AS易感性的相关性。结果：OPG基因SNP rs2073618、rs4355801位点的等位基因及基因型分布均符合Hardy—Weinberg平衡。AS组与对照组等位基因频率分别如下。rs2073618（G）：71．0％、71．9％,（C）：29．0％、28．1％;rs4355801（G）：27．7％、26．4％,（A）：72．3％、73．6％。两组在基因型频率的分布上显示,m2073618（CC）：9．2％、8．9％,（GC）：39．5％、38．4％,（GG）：51．3％、52．7％;rs4355801（AA）：52．3％、52．7％,（AG）：40．0％、41．9％,（GG）：7．7％、5．4％。以上数据组间比较差异均无统计学意义（P〉0．05）。经关联性分析,未发现AS发病的风险等位基因或基因型。结论：中国大陆汉族人群中OPG基因SNP rs2073618、rs4355801单核苷酸多态性与AS的易感性之间没有相关性。     

ABCB1和ABCC2基因多态性与中国汉族儿童抗结核药物致肝毒性易感性的相关性研究

目的 探讨ABCB1和ABCC2基因多态性与中国汉族儿童抗结核药物致肝毒性(anti-tuberculosis drug-induced hepatotoxicity,ATDH)易感性的相关性.方法 在中国汉族结核病患儿中,采用病例对照研究,利用高通量的MassARRAY平台,对于ABCB1和ABCC2基因的16个标签单核苷酸多态性(single nucleotide polymorphisms,SNPs)位点展开基因分型,并采用logistic回归分析以上SNP位点等位基因和基因型频率在ATDH病例组和ATDH对照组中的分布差异.结果 本研究共纳入41例ATDH病例以及189例对照.ABCB1和ABCC2基因SNP位点的等位基因以及基因型在两组间频率分布差异均无统计学意义(P＞0.05).SNP位点分别按照显性遗传模型和隐性遗传模型分析,各位点基因型在两组间频率分布差异均无统计学意义(P＞0.05).结论 ABCB1和ABCC2基因多态性可能与中国汉族儿童ATDH的发生并无相关性.