狼疮易感基因PBX1 3''端非翻译区的结构变异及其功能分析

目的对中国人群系统性红斑狼疮（SLE）易感基因前B淋巴细胞白血病转录因子（PBXl）3’端非翻译区的结构变异进行分析及功能研究。方法利用焦磷酸测序技术（Ryrosequencing）对273名正常人，633例狼疮患者标本进行rs3185695基因分型，进行病例对照研究。通过实时定量聚合酶链反应（PCR）、Pyrosequencing以及报告基因活性测定等方法进行等位基因特异性基因表达研究，分析PBXl基因3’端非翻译区的rs3185695对基因表达的影响。结果中国人群中rs3185695次要等位基因A在SLE患者组和正常对照组的频率分别为11．4％和4．2％，差异具有统计学意义（P〈0．01），次要等位基因A与SLE发病相关。rs3185695为A／G杂合子的cDNA样本中PBXl基因的mRNA水平表达量明显低于G／G纯合子，带有A等位基因的转录本水平明显低于G等位基因。rs3185695A等位基因的重组质粒报告基因的活性明显低于G等位基因。结论中国人群中PBXl基因3’端非翻译区的rs3185695A与SLE发病关联，该单核苷酸多态性（SNP）位点G→A的变异能下调PBXl基因的表达，继而调节其调控通路下游基因的转录水平，参与疾病的发生。     

系统性红斑狼疮候选基因OAZ中单核苷酸多态性的系统筛选及相关分析

目的研究OLFl／EBF相关锌指蛋白基因（OAZ）上的单核苷酸多态性（SNP）与中国人群系统性红斑狼疮（SLE）发病的相关性。方法利用243个中国SLE患者核心家系DNA．依据http：／／www．hapmap．org/数据库中的信息，选取了OAZ基因上的35个SNP位点进行等位基因分型，以Haploview、Genehunter和Fbat生物信息学软件分析其与中国人SLE发病的相关性。结果对等位基因分型结果进行家系传递不平衡检验（TDT），提示rsl420683，rs6500240显示传递不平衡，rsl420683等位基因G优势传递给患者，传递：不传递=86：50，P=0．002；rs6500240等位基因C优势传递给患者，传递：不传递=88：56，P=0．008。结论OAZ基因上的SNP位点rs1420683和rs6500240与SLE发病相关．未发现这两个位点的突变影响转录因子的结合，并且相互之间并没有存在强的连锁关系，可能与邻近的某个影响蛋白结构或表达的功能性SNP存在连锁不平衡，需要进一步研究证实。     

在中国人群中鉴定发现PBX1基因为1q 23-24区域新的狼疮易感基因

目的用连锁不平衡(linkage disequilibrium)的方法对1号染色体狼疮易感区域进行进一步的精细定位,并由此定位新的系统性红斑狼疮(SLE)候选基因.方法用9对高密度的微卫星标记对1q23-24易感区域进行连锁不平衡分析;用延伸型传递不平衡试验(ETDT)、Gene Hunter和家系为基础的相关分析(FBAT)软件分析连锁不平衡的结果;用TaqMan荧光实时定量聚合酶链反应(PCR)检测候选基因mRNA的表达量;用等位基因分型PCR对候选基因内的4个SNP分型.结果①发现微卫星标记D1S2628 (P＝0.000 987,Pc＝0.001 2)和D1S2673 (P＝0.007 082,Pc＝0.010 4)的等位基因存在整体的显著传递不平衡);②发现D1S2628-119 bp (Pc＝0.001 2;传递∶不传递＝91∶45,P＝0.000 1)和D1S2673-103 bp (Pc＝0.010 4,传递∶不传递＝109∶67,P＝0.0016)等位基因从杂合子父母优势传递给受累后代;③在中国汉族红斑狼疮核心家系中单倍型D1S2628 (119 bp)-D1S2673 (103 bp) (传递∶不传递＝43∶18,P＝0.001 4)和单倍型D1S2628 (119 bp)-D1S2673 (107 bp) (传递∶不传递＝29∶12,P＝0.007 9)存在传递不平衡.在中国汉族SLE患者中PBX1的mRNA的表达量显著下降(P＜0.000 1).PBX1基因中的单倍型SNP1(G)-SNP2(C)优势传递给受累后代.结论在中国汉族人群的1q23区存在与微卫星标记D1S2628和D1S2673物理距离相近的SLE易感基因;PBX1基因表达较低,其SNP单倍型与SLE易感显著相关.这提示PBX1基因可能是一个新的候选基因.     

Ⅰ型干扰素受体基因的变异与中国人群狼疮肾炎发病的相关性研究

目的研究Ⅰ型干扰素受体基因内部的单核苷酸多态性(SNP)与中国人群狼疮肾炎发病的相关性。方法选择IFNAR1和IFNAR2内部的14个SNP标记在200个核心家系,537例系统性红斑狼疮(SLE)患者(203例狼疮肾炎患者和334例狼疮非肾炎患者)和252名正常人中进行等位基因分型,以Haploview软件分析SNP分布情况,并用FBAT软件做TDT分析。结果发现中国汉族人群中①IFNAR1-SNPrs2243594等位基因频率(G)在SLE患者(29.0%)和正常人(21.2%)中差异有统计学意义(P<0.01)。AA基因型的频率在SLE患者(50.3%)低于正常对照组(61.2%,P<0.05)。②IFNAR1-SNPrs2243594等位基因频率(G)在狼疮肾炎患者(35.5%)和正常人(21.2%)两组对象的差异有统计学意义(P<0.01)。AA基因型的频率在狼疮肾炎患者(39.1%)低于正常对照组(61.2%,P<0.01)。③IFNAR1含有rs2243594G等位基因的单倍型频率在SLE肾炎患者与正常人差异有统计学意义(P<0.05)。④rs2243594G等位基因在肾炎家系中有优势传递。结论IFNAR基因的变异可能在狼疮肾炎发病中发挥作用。     

PPAP2B基因单核苷酸多态性与冠心病的关联研究

目的研究PPAP2B基因单核苷酸多态性(SNP)位点与中国汉族人冠心病(CHD)发病的相关性。方法共收集525例CHD患者和650例正常对照(NC),采用病例-对照关联研究的方法 ,选取PPAP2B基因的4个标签SNP,包括已有报道的rs17114036位点,采用单碱基延伸法(SNaPshot)进行基因分型,并分析其与冠心病的相关性。结果 PPAP2B基因4个标签SNP:rs6588635、rs17114036、rs2404715和rs17407790的基因型分布均符合Hardy-Weinberg平衡(P>0.05)。其等位基因频率在CHD组与NC组间有显著差异(rs6588635P=0.00167、rs17114036P=0.00581、rs2404715P=0.0174、rs17407790P=0.00124)。通过单倍体型分析发现,这4个SNP位点处于同一个连锁不平衡区域,其中风险单倍体型TACC可以增加冠心病易感性0.73倍(P=0.0012),而保护型的单倍体型CGTT可降低冠心病的患病风险47%(P=0.0025)。结论 PPAP2B基因SNP位点与冠心病发病显著相关,其危险等位基因可增加冠心病的易感性。     

IRGM和ATG16L1基因多态性与中国汉族人群克罗恩病的相关性

目的分析IRGM和ATG16L1基因多态性与中国汉族人群克罗恩病(crohn’s disease,CD)发病的相关性。方法选取中国汉族CD患者和健康对照者各318例纳入研究,采用聚合酶链式反应和直接测序方法检测其IRGM和ATG16L1基因的基因型,比较两组间基因型和等位基因频率。结果 CD组和正常对照组IRGM基因rs13361189位点、ATG16L1基因rs2241880位点基因型和基因频率分布均符合Hardy-Weinberg遗传平衡定律,两组间2种基因相应的SNP位点的基因型和等位基因频率差异均无统计学意义(P>0.05)。结论虽然IRGM和ATG16L1基因的遗传变异与西方白种人CD的易感性相关,但是IRGM和ATG16L1基因多态性却与中国汉族人CD无明显相关性。     

尾加压素Ⅱ基因多态性与多囊卵巢综合征相关性的研究

目的 探讨尾加压素Ⅱ(UTS2)基因多态性与多囊卵巢综合征(PCOS)发病的关系.方法 用熔解温度不同的基因分型法.检测PCOS患者101例(PCOS组)及其父母202名和105名健康妇女(对照组)UTS2基因rs228648、rs2890565位点单核苷酸多态性(SNP),并检测基础状态下FSH、LH、睾酮、空腹血糖、空腹胰岛素水平.结果 PCOS组的UTS2基因rs228648 A/G多态性位点与对照组比较,基因型与等位基因频率均无明显差异,两组的SNP rs2890565基因型频率差异有统计学意义(P<0.05),PCOS组A等位基因频率明显高于对照组(P<0.05).传递不平衡检验(TDT)显示,SNP rs228648A/G在杂合子父母的2个不同等位基因无优势传递(P>0.05),而rs2890565 A/G在杂合子父母A等位基因优势传递(P<0.05).PCOS组UTS2基因SNP rs228648 GG基因型较携带A等位基因的PCOS患者稳态模型评估的胰岛素抵抗指数(HOMA-IR)明显增高(P<0.05).SNP rs2890565从和AG基因型空腹血糖、空腹胰岛素较GG基因型明显增高,从基因型HOMA-IR较GG基因型明显增高(P<0.05).结论 UTS2基因SNP rs228648 A/G多态性与PCOS无相关性,但与胰岛素抵抗存在关联.UTS2基因SNP rs2890565可能在PCOS的遗传易感性中起一定作用,A等位基因可能与PCOS的发生有关.     

磷酸二酯酶4D基因单核苷酸多态性与COPD相关性研究

目的 探讨磷酸二酯酶4D (PDE4D)基因单核苷酸多态性(SNP)与COPD相关性.方法 选取8个SNP位点SNP1=rs11740402,SNP2=rs17528473,SNP3=rs17780213,SNP4=rs1529843,SNP5=rs11743928,SNP6=rs26956,SNP7=rs35387,SNP8=rs35386,以北京某社区40～80岁人群为研究对象,共入选136例受试者,COPD组71例和对照组65例,均为汉族.设计目标SNP位点上下游引物,PCR扩增目标片段,Sanger测序法检测目标片段碱基,x2检验比较2组在等位基因和基因型分布频率上的差异,非条件Logistic回归评价SNP位点与COPD之间的相关性.结果 8个SNP位点其基因型分布在COPD组和对照组均符合Hardy-Weinberg平衡,在对照组受试者连锁不平衡(Linkage Disequilibrium,LD)分析时发现SNP1、SNP2处于连锁不平衡,形成LDBlock1,SNP6、SNP7和SNP8处于连锁不平衡,形成LD Block2,SNP5基因型均为A/A型,不能与其他SNP位点形成LD Block.单倍体型分析发现在COPD组和对照组中差异无统计学意义(P＞0.05).基于等位基因的关联分析中发现2组病例之间差异无统计学意义(P＞0.05),在基因型的关联分析中发现位点SNP8基因型频率在COPD组和对照组差异有统计学意义(P＜0.05),在进一步非条件Logistic回归分析中发现SNP8在Ressessive遗传模型时与COPD存在相关性,G/G基因型在COPD组和对照组分别为20.3％和6.3％(P＜0.05,OR =4.07,95％ CI为1.26～13.18),提示SNP8的G/G基因型与COPD易感性增加有关.结论 研究结果提示PDE4D基因SNP可能与COPD的发生发展相关,SNP8的G/G基因型可能是COPD易感性的一个预测因子.     

系统性红斑狼疮患者脱氧核糖核酸酶1基因多态性研究

目的：探讨脱氧核糖核酸酶1（DNASE1）基因单核苷酸多态性（SNP）与中国人系统性红斑狼疮（SLE）相关性。方法：验证文献报道的DNASE1基因3′端4个SNP，选取杂合度较高者对312个中国人群SLE家系以TaqManMGB等位基因识别技术在ABI7900HT序列测定仪上进行SNP基因分型，数据以SDS2．0软件收集，Genehunter进行统计处理并构建SNP单倍型。结果：中国人群中，DNASE1SNP3398，3737杂合度均接近0．5，4184亦有一定的杂合度。3398与3737的C－G单倍型优先传递给患病子代，3398、3737，4184的单位型C－G－G优先传递给患病子代（P＜0．05）。结论：在SLE患者中存在特定的SNP单倍型，部分SLE患者的发病与DNASE1基因相关联。     

SEPT14基因单核苷酸多态性与散发性帕金森病的相关性研究

目的探讨鲁西南地区汉族人群SEPT14的4个单核苷酸多态性(single nucleotide polymorphisms,SNP)与散发性帕金森病(Parkinsons disease,PD)是否具有相关性。方法收集鲁西南地区的180例PD患者(病例组)和200例健康对照者(对照组),均为汉族,通过PCR和测序法,比较2组SEPT14基因的4个SNP(rs77231105、rs10241628、rs11981883、rs73701167)的等位基因和基因型频率的分布差异。结果病例组与对照组中的rs77231105、rs10241628和rs11981883的等位基因和基因型频率分布比较,差异无统计学意义(P0.05)。病例组与对照组rs73701167的TT、CC基因型比例和C等位基因频率比较,差异有统计学意义(50.0%vs 66.5%,12.2%vs7.5%,P=0.005;31.1%vs 20.5%,P=0.001,OR=1.75,95%CI:1.261~2.428)。结论 SEPT14基因的SNP位点rs77231105、rs10241628和rs1198188与鲁西南地区汉族人群PD的发病无相关性。而SNP位点rs73701167与鲁西南地区汉族人群PD的发病具有相关性,等位基因C可能是其发病的危险因素。     

Association of IRF5 polymorphisms with systemic lupus erythematosus in a Japanese population: support for a crucial role of intron 1 polymorphisms

OBJECTIVE: To determine whether the IRF5 gene, which encodes interferon regulatory factor 5, is associated with systemic lupus erythematosus (SLE) in a Japanese population. METHODS: A case-control study was performed in 277 SLE patients and 201 healthy controls. Associations between the IRF5 genotype and levels of messenger RNA (mRNA) for interferon (IFN) pathway genes were examined using an mRNA expression database of HapMap samples. RESULTS: Carriers of the rs2004640T single-nucleotide polymorphism (SNP) were slightly increased among SLE patients (58.8%) as compared with controls (50.2%). When data from our Japanese population were combined with previously published data from a Korean population, the T allele frequency was found to be significantly increased in SLE patients (P = 8.3 x 10(-5)). While no association was observed for the rs10954213 SNP or the exon 6 insertion/deletion, significant associations with 3 intron 1 SNPs (-4001, rs6953165, and rs41298401) were found. The allele frequency of rs41298401G was significantly decreased in SLE patients (13.0% versus 18.7% in controls; P = 0.017), and the allele frequency of rs6953165G, which was in absolute linkage disequilibrium with -4001A, was increased in SLE patients (8.8% versus 5.2% in controls; P = 0.034). The Caucasian risk haplotype was not present; instead, a protective haplotype carrying rs2004640G, rs41298401G, the deletion in exon 6, and rs10954213A was identified. SNP rs10954213, but not intron 1 SNPs, was associated with IRF5 at the mRNA level; nevertheless, intron 1 SNPs were also associated with levels of mRNA for several IFN pathway genes, suggesting a functional role. CONCLUSION: IRF5 was found to be associated with SLE in Asian populations. Intron 1 SNPs, rather than exon 6 and 3'-untranslated region polymorphisms, appeared to play a crucial role.     

Variation in the ICAM1-ICAM4-ICAM5 locus is associated with systemic lupus erythematosus susceptibility in multiple ancestries

OBJECTIVE: Systemic lupus erythematosus (SLE; OMIM 152700) is a chronic autoimmune disease for which the aetiology includes genetic and environmental factors. ITGAM, integrin α(M) (complement component 3 receptor 3 subunit) encoding a ligand for intracellular adhesion molecule (ICAM) proteins, is an established SLE susceptibility locus. This study aimed to evaluate the independent and joint effects of genetic variations in the genes that encode ITGAM and ICAM. METHODS: The authors examined several markers in the ICAM1-ICAM4-ICAM5 locus on chromosome 19p13 and the single ITGAM polymorphism (rs1143679) using a large-scale case-control study of 17 481 unrelated participants from four ancestry populations. The single-marker association and gene-gene interaction were analysed for each ancestry, and a meta-analysis across the four ancestries was performed. RESULTS: The A-allele of ICAM1-ICAM4-ICAM5 rs3093030, associated with elevated plasma levels of soluble ICAM1, and the A-allele of ITGAM rs1143679 showed the strongest association with increased SLE susceptibility in each of the ancestry populations and the trans-ancestry meta-analysis (OR(meta)=1.16, 95% CI 1.11 to 1.22; p=4.88×10(-10) and OR(meta)=1.67, 95% CI 1.55 to 1.79; p=3.32×10(-46), respectively). The effect of the ICAM single-nucleotide polymorphisms (SNPs) was independent of the effect of the ITGAM SNP rs1143679, and carriers of both ICAM rs3093030-AA and ITGAM rs1143679-AA had an OR of 4.08 compared with those with no risk allele in either SNP (95% CI 2.09 to 7.98; p=3.91×10(-5)). CONCLUSION: These findings are the first to suggest that an ICAM-integrin-mediated pathway contributes to susceptibility to SLE.     

Association of a non-synonymous single-nucleotide polymorphism of DNASEI with SLE susceptibility

OBJECTIVES: To investigate the association of a non-synonymous single-nucleotide polymorphism (SNP) in DNASEI with susceptibility to systemic lupus erythematosus (SLE) and the production of autoantibodies to nuclear antigens. METHODS: The Gln244Arg (rs1053874) SNP was studied in 276 SLE patients and in 368 healthy controls of Spanish ancestry. Its relationship with SLE susceptibility, serum DNase I activity, anti-ribonucleoprotein (RNP), anti-double-stranded DNA (dsDNA), anti-nucleosome and anti-single-stranded DNA (ssDNA) antibodies was determined. RESULTS: An association of the Gln244Arg SNP with SLE susceptibility that followed a recessive genetic model (P=0.002) was found. The GG genotype was more common in SLE patients (59.8%) than in controls (47.3%). However, the Gln244Arg genotype did not correlate with DNase I activity in sera from SLE patients or from controls. In addition, the Gln244Arg SNP did not influence autoantibody titres significantly. CONCLUSION: The association of the Gln244Arg SNP with SLE susceptibility indicates that common polymorphisms in DNASEI play a role in the genetics of SLE. However, the lack of effect of the Gln244Arg SNP on serum DNase I activity calls into question the direct involvement of this specific SNP.     

Variants in Intron 4 of PD-1 Gene are Associated with the Susceptibility to SLE in an Iranian Population

Background: Programmed cell death protein 1 (PD-1) is a negative costimulatory molecule with immunomodulatory properties. Recently, PD-1 gene defects have attracted attention in the pathogenesis of SLE. Objective: Here, we assessed the association of PD-1 gene polymorphisms in intron 4 and haplotypes with the susceptibility to SLE. Method: Seventy-six SLE patients and 159 healthy controls were included. We screened the polymorphisms by amplifying the intron 4 of the PD-1 gene with the specific primers followed by sequencing. Results: Two distinct SNPs were identified (rs6705653 and rs41386439) within the intron 4 of the PD-1 gene. The AA genotype of +7499 (G/A) SNP was associated with the higher risk of SLE [OR=3.31, 95% CI (1.25-8.76), p-value=0.045], while A allele was identified as a risk allele [OR=1.75, 95% CI (1.10-2.76), p-value=0.015]. However, no significant association was observed between the allele and the genotype frequencies of +7209 (C/T) polymorphic region of the PD-1 gene and susceptibility to SLE. Haplotype analysis showed the significantly higher presence of H2 haplotype (AC; +7499/+7209) [OR=1.70, 95% CI (1.24-2.33), p-value=0.0012] in SLE patients. Conclusion: To the best of our knowledge, this is the first report of the significant association of PD-1 +7499 (G/A) SNP with the SLE susceptibility and the first detection of both polymorphic loci in a population from Iran. However, more investigations are necessary to confirm these findings.     

Two single-nucleotide polymorphisms in the 5' and 3' ends of the osteopontin gene contribute to susceptibility to systemic lupus erythematosus

OBJECTIVE: To test the association of osteopontin (OPN) polymorphisms with systemic lupus erythematosus (SLE). METHODS: The coding 5' and 3' flanking regions of the OPN gene were scanned for polymorphisms by denaturing high-performance liquid chromatography. A case-control association study was performed in 394 Italian SLE patients and 479 matched controls. OPN serum levels were determined by enzyme-linked immunosorbent assay in 40 patients and 124 controls, and the mean levels were compared between the different OPN genotypes. RESULTS: Among the 13 detected single-nucleotide polymorphisms (SNPs), alleles -156G (frequency 0.714 versus 0.651; P = 0.006, corrected P [P(corr)] = 0.036) and +1239C (0.377 versus 0.297; P = 0.00094, P(corr) = 0.0056) were significantly increased in the SLE patients compared with the controls. The presence of the associated allele in single or double dose conferred an odds ratio (OR) of 2.35 (95% confidence interval [95% CI] 1.38-4.02) for SNP -156 and an OR of 1.57 (95% CI 1.16-2.13) for SNP +1239. These effects were independent of each other, i.e., not a consequence of linkage disequilibrium between the 2 alleles. The risk associated with a double dose of susceptibility alleles at both SNPs was 3.8-fold higher (95% CI 2.0-7.4) relative to the complete absence of susceptibility alleles. With regard to individual clinical and immunologic features, a significant association was seen between lymphadenopathy and -156 genotypes (overall P = 0.0011, P(corr) = 0.046). A significantly increased OPN serum level was detected in healthy individuals carrying +1239C (P = 0.002), which is indicative of an association between the SLE susceptibility allele and OPN levels. CONCLUSION: These data suggest the independent effect of a promoter (-156) and a 3'-untranslated region (+1239) SNP in SLE susceptibility. We can speculate that these sequence variants (or others in perfect linkage disequilibrium) create a predisposition to high production of OPN, and that this in turn may confer susceptibility to SLE.     

Association study of Toll-like receptor 5 (TLR5) and Toll-like receptor 9 (TLR9) polymorphisms in systemic lupus erythematosus

OBJECTIVE: Toll-like receptors (TLR) play an important role in both adaptive and innate immunity. Variations in TLR genes have been shown to be associated with various infectious and inflammatory diseases. We investigated the association of TLR5 (Arg392Stop, rs5744168) and TLR9 (-1237T-->C, rs5743836) single nucleotide polymorphisms (SNP) with systemic lupus erythematosus (SLE) in Caucasian American subjects. METHODS: We performed a case-control association study and genotyped 409 Caucasian women with SLE and 509 Caucasian healthy female controls using TaqMan allelic discrimination (rs5744168) or polymerase chain reaction-restriction fragment length polymorphism analysis (rs5743836). RESULTS: None of the 2 TLR SNP showed a statistically significant association with SLE risk in our cohort. CONCLUSION: Our results do not indicate a major influence of these putative functional TLR SNP on the susceptibility to (or protection from) SLE.     

中国汉族人群系统性红斑狼疮患者信号传导和转录激活子4基因多态性研究

目的 探讨信号传导和转录激活子4(STAT4)基因多态性与中国汉族人群系统性红斑狼疮(SLE)的相关性.方法 运用焦磷酸测序的方法对SLE患者与健康对照组DNA中存在的3个单核苷酸多态性位点进行分型,并作统计学分析.结果 STAT4基因的3个单核苷酸多态性(SNP)及其构成的单倍型在患者与健康对照组间差异均有统计学意义[rs11889341:P=012 02,0R(95%CI)=1.22(1.044～1.424);m7574865:P=0.003 454,OR(95%CI)=1.25(1.076～1.451);rs8179673:P=0.004 275,OR(95%CI)=1.274(1.079～1.505)].结论 STAT4基因上ra11889341、rs7574865和rs8179673与中国汉族人群SLE的发病有关联,且STAT4是-个多种族均存在的SLE相关基因.     

bcl-2 bcl-x和bax基因多态性与系统性红斑狼疮易感相关性

目的 探讨bcl-2、bcl-X和bax基因中7个多态位点同系统性红斑狼疮(SLE)是否存在相关性。方法 采用引物引入限制性内切酶分析(PIRA-PER)、四引物扩增阻滞突变系统以及单链构象多态性(SSCP)技术，分析100名正常人和88例SLE患者bcl-2基因的3个单核苷酸多态性(SNP)位点(dbSNP：rs1800477，rsl801018．rs1564483)、bcl-x基因的3个SNP位点(dbSNP：rs6060900，rs6089046，rs5841091)及bax基因的1个微卫星位点。以Logistic回归分析统计实验数据。结果 SLE患者组bcl-2基因rs1800477位点的GG基因型频率高于正常人群(P=0．013)，rs1564483位点GG基因型频率则低于正常人群(P=0．024)；rs1801018位点则无统计学意义。bcl-x和bax的所选位点均没有表现出多态性。结论 bcl-2基因rs1800477和rs1564483两位点多态性可能与SLE相关。