血管生长素基因与中国汉族人群糖尿病周围神经病遗传易感性的关系

目的探讨血管生长素（ANG）基因与中国汉族人群糖尿病周围神经病（DPN）遗传易感性的关系。方法采用病例一对照研究方法,对129例DPN患者和268例健康对照者,应用基因测序技术,检测ANG基因外显子区序列,分析比较DPN患者和健康对照者之间基因型和等位基因分布频率的差异。结果①PCR扩增产物片段长度为736bp,包含ANG基因整个外显子区和5’侧翼区,DPN组未检测出ANG基因突变;②DPN组和健康对照组的ANG基因外显子区单核苷酸多态性rs11701的基因型（T442T和T442G）和等位基因频率（442T和442G）比较后,差异无统计学意义,P〉0．05;③按性别分层后,DPN组和健康对照组的ANG基因外显子区单核苷酸多态性（SNP）rs11701的基因型和等位基因频率比较后,差异均无统计学意义,两组P〉0．05。结论ANG基因与中国汉族人群DPN遗传易感性无关。     

浙江温州地区人群染色体9p21上rs1333049位点的单核苷酸多态性分布与冠心病的相关性

目的研究浙江温州地区汉族人群中染色体9p21上的rs1333049位点上的单核苷酸多态性（single nucleotide polymorphism,SNP）与冠心病的相关性。方法对冠心病组（至少1支主要冠状动脉内径狭窄≥50.00%）181例和对照组173例,采用聚合酶链反应和基因测序方法,检测染色体9p21上rs1333049位点基因多态性。结果 3种基因型均可在rs1333049位点上检测到,并且其基因型的分布亦符合Hardy-Weinberg平衡定律。冠心病组rs13330^149位点的CC、CG基因型分布及C等位基因频率均高于对照组,差异有统计学意义（均P〈0.01）。结论 rs1333049位点G/C基因的多态性与冠心病发病相关,其中的C等位基因亦可能是浙江温州地区汉族人群冠心病患者的易感性标志之一。     

IL-6R基因单核苷酸多态性与肺结核易感性的相关性研究

目的探讨白细胞介素-6受体（Interleukin-6R,IL-6R）基因多态性与汉族人群肺结核发病的关系。方法分析深圳汉族人群中96例结核病患者和96名健康对照的IL-6R基因rs1552481、rs4379670、rs3887104、rs2229238位点的多态性,分析基因多态性与结核病易感性的关系。结果 IL-6R基因rs4379670位点,病例组TA基因型频率（25.3）明显低于对照组（39.8）（P〈0.05）,病例组T等位基因频率（14.7）明显低于对照组（24.2）（P〈0.05）;rs2229238位点,对照组TC基因型频率（25.3）明显低于病例组（37.9）（P〈0.05）,病例组T等位基因频率（14.7）也明显低于对照组（24.2）（P〈0.05）;其他两个位点病例组和对照组之间无明显差异。结论 IL-6R基因rs4379670位点AA型和rs2229238位点CC型可能与肺结核发病相关,两位点中等位基因T可能为保护性基因。     

色素上皮衍生因子启动子区基因多态性与糖尿病微血管病变的关系

目的观察色素上皮衍生因子（PEDF）启动子区单核苷酸多态性（SNP）与糖尿病微血管病变的关系。方法将271例T2DM患者分为无糖尿病微血管病变组105例,合并糖尿病微血管并发症组166例,分析PEDF基因启动子区rs12150053T／C及rs12948385G／A的基因型和等位基因频率。结果两个SNPs位点等位基因频率均有统计学差异（P〈0．05）,rs12948385位点基因型频率也有统计学差异（P〈0．05）。结论PEDF启动子区多态性位点可能是我国北方汉族人群糖尿病微血管病变发病的危险因素之一。     

乙酰辅酶A羧化酶B基因多态性与2型糖尿病的相关性研究

目的探讨乙酰辅酶A羧化酶B(ACACB)基因(rs2268388及rs2268393)多态性与中国昆明地区汉族人群T2DM的相关性。方法分别运用聚合酶链反应-限制性片段长度多态性(PCRRFLP)技术及Taqman探针技术,在昆明地区汉族人群中对184例T2DM患者和70名健康对照者(NC)的ACACB基因(rs2268388及rs2268393)多态性进行检测,并比较分析各组间基因型、等位基因频率、相关临床和生化指标。结果 T2DM组和NC组ACACB基因rs2268393各基因型和等位基因频率比较,差异无统计学意义(χ2=4.810,P=0.09;χ2=1.29,P=0.24);T2DM组ACACB基因rs2268388AA基因型和A等位基因频率高于NC组(χ2=10.469,P=0.005;χ2=4.71,P=0.007);T2DM组ACACB基因rs2268388及rs2268393位点AABB基因型分布频率高于NC组(χ2=10.526,P=0.001);AABB基因型是T2DM发生的危险因素(OR:1.44,95%CI:1.32~1.57);二分类Logistic回归分析表明,ACACB基因rs2268388AA基因型、高BMI及高WHR是T2DM发生的危险因素,HDL-C是T2DM发生的保护因素。结论在昆明地区汉族人群中,ACACB基因rs2268388AA基因型可能与T2DM发生相关。     

中国汉族人群高血压脑出血患者NFATC1基因rs754093多态性观察

目的观察中国汉族人群高血压脑出血患者活化T细胞核因子1（NFATC1）基因rs754093的多态性。方法选择中国汉族人脑出血患者230例（观察组）和健康体检者233例（对照组）,采用多聚酶链反应一限制性内切酶片段长度多态性技术（PCR—RFLP）检测其血清中NFATC1基因rs754093的多态性。结果观察组基因型T／T、T／G、G／G及等位基因T、G的频率分别为34．1％、48．3％、17．4％、58．5％、41．5％,对照组分别为44．2％、44．6％、11．2％、66．5％、33．5％,两组比较,P均〈0．05。分析显示,相对于携带TT基因型者,携带GG＋TG基因型者脑出血发病风险增加51．4％;相对于携带T等位基因,携带G等位基因脑出血发病风险增加41．1％。结论中国汉族人群高血压脑出血患者NFATC1基因rs754093存在多态性,其中携带G／G基因型者易发生脑出血。     

HLA-G基因14bp插入/缺失多态性与系统性红斑狼疮的相关性

目的检测系统性红斑狼疮（systemic lupus erythematosus,SLE）患者人白细胞抗原G（human leukocyte antigen G,HLA-G）14bp插入/缺失多态性的基因型分布,明确其多态性与SLE易感性的关系。方法采用聚合酶链反应（polymerase chain reaction,PCR）检测231例SLE患者及367名健康体检者的HLA-G14bp插入/缺失多态性的基因型分布,并分析不同基因型SLE患者的临床特征。结果SLE患者及健康体检者的HLA-G14bp插入/缺失多态性基因型和等位基因分布处于Hardy-Weinberg平衡（SLE组：χ2=1.383,P=0.501;健康体检组：χ2=0.095,P=0.953）。该多态性等位基因及基因型频率在SLE组和健康体检组间分布无统计学差异（P均〉0.05）。进一步分析HLA-G14bp多态性与SLE患者的临床特征发现,不同HLA-G14-bp基因型SLE患者之间临床症状、疾病活动性积分（systemic lupus erythematosus disease activity index,SLEDAI）亦均无统计学差异（P均〉0.05）;但抗Histone抗体阳性SLE患者-14bp/-14bp基因型频率、抗U1-snRNP抗体阳性SLE患者＋14bp/-14bp基因型频率均明显增高（P值分别为0.002及0.036）。结论HLA-G14bp插入/缺失多态性与SLE易感性无关,但可能参与SLE自身抗体（抗Histone抗体及抗U1-snRNP抗体）的生成。     

TCF7L2基因单核苷酸多态性与汉族2型糖尿病遗传易感性关系的研究

目的探讨TCF7L2基因单核苷酸多态性与汉族人2型糖尿病遗传易感性的关系。方法无血缘关系江苏地区汉族人1535例,分为2型糖尿病组（T2DM）、糖耐量减低组（IGT）和正常糖耐量组（NGT）,LDR法检测TCF7L2基因rs7903146（C／T）及rs12255372（G／T）单核苷酸多态性。结果（1）T2DM、IGT组rs7903146位点T等位基因频率均高于NGT组,但差异无统计学意义;（2）糖代谢异常组rs7903146位点CT基因型频率及T等位基因频率则显著高于NGT组（P均〈0．05）,T等位基因参与糖代谢异常发生的相对风险为1．589,人群归因危险度为2．1％。结论TCF7L2基因单核苷酸多态分布存在明显的种族异质性,rs7903146位点T突变可能是中国汉族人群糖代谢异常发生的遗传因素之一。     

Pitx3基因多态性与帕金森病易感性的相关性研究

目的探讨Pitx3基因多态性与帕金森病(PD)易感性的关系。方法选择江苏地区汉族的215例PD患者作为PD组,同期选择健康体检者250例作为对照组,利用多重连接酶链反应方法,检测2组Pitx3 2个单核苷酸多态性(SNP)位点rs2281983和rs3758549基因分布,分析各基因型、等位基因频率、单倍型与PD易感性的关系。结果 PD组与对照组Pitx3基因SNP位点rs2281983的CC、CT和TT基因型(6.5%vs 7.2%,42.3%vs 41.2%,51.2%vs 51.6%,χ2=0.274,P=0.717)和等位基因频率(χ2=0.159,P=0.423)分布比较,差异无统计学意义。PD组与对照组rs3758549的CC、CT和TT基因型(57.8%vs 66.4%,34.4%vs 29.2%,7.9%vs 4.4%,χ2=9.144,P=0.023)和等位基因频率(χ2=10.138,P=0.011)分布比较,差异有统计学意义。2组Pitx3基因C-C、C-T单倍型分布比较,差异无统计学意义(P>0.05);与对照组比较,PD组T-T单倍型增加PD易感性(OR=1.299,95%CI:1.003¹.863,P=0.048)。结论江苏地区汉族人群中,Pitx3基因的rs3758549位点基因型分布和等位基因频率与PD易感性之间有显著关联性,Pitx3基因的单倍型TT可能与PD易感性相关。     

金属硫蛋白基因多态性与昆明地区汉族2型糖尿病的相关性研究

目的 探讨金属硫蛋白(MT)1A基因rs8052394多态性与昆明地区汉族T2DM的相关性。方法 采用Taqman实时荧光定量PCR技术对257例T2DM患者(T2DM组)和108名健康对照(NC)组MT1A基因型进行检测。结果 T2DM组MT1A基因rs8052394A/A基因型频率及A等位基因频率高于NC组(χ~2=20.519、29.213,P0.01)。Logistic回归分析显示,MT1A rs8052394A/A基因型携带者相对于A/G和G/G基因型携带者患T2DM的危险性增加。结论 昆明地区汉族人群MT1A基因rs8052394多态性可能与T2DM的发生有关,A等位基因可能增加T2DM的发病风险。     

Association between the rs2004640 functional polymorphism of interferon regulatory factor 5 and systemic lupus erythematosus: a meta-analysis

The aim of this study is to determine whether the functional interferon regulatory factor 5 (IRF5) polymorphism, rs2004640, confers susceptibility to systemic lupus erythematosus (SLE) in multiple ethic populations. A meta-analysis was conducted on the T allele of the IRF5 rs2004640 polymorphism and 12 studies were included in the meta-analysis. Meta-analysis revealed an association between SLE and the IRF5 rs2004640 T allele in all subjects without inter-study heterogeneity (OR 1.429, 95% CI 1.359–1.503, P < 0.001). The IRF5 rs2004640 T allele was significantly associated with SLE in European and Asians. The Asian population had a much lower prevalence of the T allele (34.4%) than any other population studied. and Europeans had the highest frequency of the IRF5 rs2004640 T allele (51.8%). In conclusion, this meta-analysis confirms that the IRF5 rs2004640 polymorphism is associated with SLE susceptibility in different ethnic groups, and that its prevalence is ethnicity dependent.     

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.     

Association of interferon regulatory factor 5 (<Emphasis Type="Italic">IRF5</Emphasis>) gene polymorphisms with juvenile idiopathic arthritis

Interferon regulatory factor 5 (IRF5) is a member of IRF family which induce signaling pathways and are involved in modulation of cell growth, differentiation, apoptosis, and immune system activity. Juvenile idiopathic arthritis (JIA) is an auto-inflammatory syndrome where the inflammatory markers are believed to play a fundamental role in its pathogenesis. In this study, we aimed to assess the association of IRF5 gene polymorphisms with susceptibility of JIA in Iranian population. Three IRF5 single-nucleotide polymorphisms (rs10954213 A/G, rs2004640 G/T, and rs3807306 G/T) were genotyped using TaqMan assays in 55 patients with JIA and 63 matched healthy individuals. The frequency of the IRF5 rs2004640 T allele was significantly higher (69 vs 45%, P value?=?0.0013) in JIA group as compared to control. The frequency of the IRF5 rs 2004640 G allele was significantly higher in the control group in comparison to JIA group (54 vs 32%, P value?=?0.001). Allele and genotype frequencies of the rs10954213 and rs3807306 did not show any significant difference between JIA and control group. IRF5 rs 2004640 T allele can be considered as a risk factor for the development of JIA and presence of rs 2004640 G may be act as protective factor.     

IRF5 rs2004640-T allele, the new genetic factor for systemic lupus erythematosus, is not associated with rheumatoid arthritis

BACKGROUND: Recently, a new genetic factor within the interferon regulatory factor 5 (IRF5) gene was demonstrated for systemic lupus erythematosus (SLE) through linkage and association: the rs2004640-T allele. IRF5 is involved in the production of rheumatoid arthritis (RA) cytokines, and SLE already shares with RA one genetic factor within the tyrosine phosphatase PTPN22 gene. AIM: To test the hypothesis that the SLE IRF5 genetic factor could also be shared with RA. PATIENTS AND METHODS: 100 French Caucasian trio families with RA were genotyped and analysed with the transmission disequilibrium test, the frequency comparison of the transmitted and untransmitted alleles, and the genotype relative risk. 97% power was available to detect at least a trend in favour of a factor similar to that reported for SLE. RESULTS: The analysis showed the absence of linkage and association globally and in "autoimmune" RA subsets, with a weak non-significant trend against the IRF5 rs20046470-T allele. Given the robustness of familial-based analysis, this slight negative trend provided strong evidence against even a weaker factor than that reported for SLE. CONCLUSION: Our results exclude the IRF5 rs2004640-T allele as a major genetic factor for RA in this French Caucasian population.     

SLC30A8基因rs13266634C/T多态性与甘肃省东乡族及回族2型糖尿病的相关性研究

目的 探讨SLC30A8基因rs13266634C/T遗传多态性与甘肃东乡族及回族T2DM的关系。 方法 应用PCR–RFLP检测甘肃东乡族、回族T2DM（T2DM组）患者和健康对照者 （NC组）者SLC30A8的基因型。 结果 东乡族、回族T2DM组CC基因型（39.07% vs 40.80%）、C等位基因（61.80% vs 62.40%）频率均高于NC组（23.30% vs 26.00%;50.00% vs 51.60%）（P〈0.05）。 结论 SLC30A8基因多态性与甘肃东乡族和回族人群T2DM发病有关,C是其风险等位基因。     

Association of the IRF5 rs2004640 polymorphism with rheumatoid arthritis: a meta-analysis

Several molecular epidemiological studies have been conducted in recent years to evaluate a possible association between the interferon regulatory factor 5 (IRF5) rs2004640 polymorphism and rheumatoid arthritis risk in diverse populations. However, the results remain conflicting rather than conclusive. Our aim was to assess associations of IRF5 gene polymorphisms with rheumatoid arthritis risk. Meta-analysis was performed on six published case–control studies (from eight countries) that included 4,818 cases of rheumatoid arthritis and 4,316 controls. The rs2004640-T allele was associated with a significantly increased risk of rheumatoid arthritis when the dominant genetic model was applied (T/T + T/G versus G/G: P = 0.003, OR = 1.14, 95 % CI 1.05–1.25). Upon stratified analysis by ethnicity, the rs2004640 polymorphism was associated with an increased rheumatoid arthritis risk in Caucasians when the homozygotic contrast model was employed(T/T versus G/G: P = 0.03, OR = 1.25, 95 % CI 1.02–1.53) and this was also the case when the dominant genetic model was used (T/T + T/G versus G/G: P = 0.04, OR = 1.20, 95 % CI 1.01–1.42), whereas, in Asian populations, only the dominant genetic model was associated with an increased rheumatoid arthritis risk (T/T + T/G versus G/G: P = 0.02, OR = 1.14, 95 % CI 1.02–1.26). The results suggest that the IRF5 rs2004640 polymorphism is associated with rheumatoid arthritis especially when the dominant genetic model is applied.