FOXP3基因多态性与斑秃的关联研究

目的探讨FOXP3基因多态性与斑秃(alopecia areata,AA)发生发展的关系。方法选择240例斑秃患者及248例正常对照。结合HapMap网站中汉族人群资料,选取rs3761547和rs3761548共2个单核苷酸多态性(single nucleotide polymorphism,SNP)位点,采用聚合酶链反应-限制性片段长度多态性(polymerase chain reaction-restriction fragment length polymorphism,PCR-RFLP)的方法进行基因分型,统计学分析单核苷酸多态性。结果与正常对照比较,斑秃患者组FOXP3基因rs3761548位点的基因型分布有差异,具有统计学意义(P=0.015);而rs3761547位点的基因型分布在正常对照组与斑秃患者组之间没有差异(P=0.12)。非条件Logistic回归分析显示,rs3761548位点的CC基因型相对于AA和AC基因型来说,对斑秃的发病具有保护效应(adjusted OR:0.69;95%CI:0.48-0.98)。单倍型分析结果显示,与对照组相比较,斑秃患者单倍型GA和单倍型GC的分布存...     

214例斑秃患者心理疏导疗效的初步观察

214例斑秃患者作为实验组,施以协同药物处方加上心理疏导治疗,与40例来自同一门诊斑秃组成对照组;性别、年龄、病程等与实验组有可比性,但仅施以协同药物处方治疗。一个疗程(三个月)后,两组相比,前者痊愈率及总有效率均显著高于后者,甲皱微循环改善情况亦呈同样趋势、表明心理治疗与药物治疗合用对斑秃近期疗效优于单纯药物治疗。     

Susceptible and protective endothelial nitric oxide synthase gene polymorphism in alopecia areata in the Kuwaiti population

Alopecia areata (AA) is a chronic inflammatory disease with evidence of T-cell involvement that causes hair follicle “immune privilege collapse”. Nitric monoxide was shown to contribute in the pathogenesis of AA. We are investigating evidence for the association of eNOS gene polymorphism with AA. Genomic DNA was extracted from 176 subjects, 87 Kuwaiti AA patients and 89 matched (for ethnicity, gender and age) healthy controls. A variable number tandem repeat (VNTR) located in intron-4 of the eNOS gene consisting of either four or five (27-base pair) repeats was analyzed by polymerase chain reaction and electrophoresis fragment analysis using ABI 3100 genetic analyzer. Haploview and GenePOP software were used for data analysis. A significant association was found between the intron-4 27 bp-VNTR and AA, where 4b was identified as the risk allele had (χ² = 4.42, p = 0.035, OR = 2.03). Genotype (4b/4b) showed a significant association with susceptibility to AA and have a frequency of 22% higher in AA patients than in healthy controls (71 vs 49%) and a χ² = 6.39, (p = 0.011, OR = 2.63). We report a significant association of a polymorphism within the eNOS gene and susceptibility to AA.     

KCNQl基因多态性与2型糖尿病易感性相关研究

目的探讨KCNQ1基因单核苷酸多态性（SNPs）与2型糖尿病易感性的关系。方法应用基质辅助激光解吸附电离飞行时间质谱（MALDFFOF—Ms）平台以及MassARRARY—iPLEX技术,分别对238例2型糖尿病患者和240例正常对照组KCNQl基因的三个单核苷酸多态性位点（rs231361、rs231359和rs2237892）进行基因分型,并分析KCNQI基因位点在两组间的差异。结果rs2237892存在CC、TC、TT三种基因型多态性,在对照组中的基因型频率分别为45．5％、40．7％、13．8％,在病例组中的基因型频率分别为44．4％、49．6％、6．0％,该位点在对照组和病例组中分布差异有统计学意义（x2=9．334,P=0．009）。相较于cc基因型,TT基因型其OR（95％CI）分别为0．416（0．206-0．840）（P=0．014）。位点rs231361和rs231359均存在三种多态性,但在病例组和对照组间差异无统计学意义。结论KCNQ1基因位点rs2237892与2型糖尿病易感性相关,位点rs231361和rs231359与2型糖尿病易感性不相关。     

Genomic variants of TLR1--it takes (TLR-)two to tango

Toll-like receptors (TLR) are innate immune sensors of microbial cell wall products that initiate early host responses. The TLR2 receptor complex has been shown to contain heterodimers of TLR2 with either TLR1 or TLR6 enabling the host to detect different microbial molecules, such as lipopeptides of different chemical composition. In this issue of the European Journal of Immunology, an important role in the sensing of microbial products for I602S, a single nucleotide polymorphism (SNP) in human TLR1 has been identified. This result, in combination with another recently published report on this polymorphism elucidating a functional role in cell trafficking (surface expression of the receptor complex in individuals carrying the SNP was altered), provide genetic evidence affirming the important function of TLR1 as an essential co-receptor for TLR2.     

精神分裂症与NOS1多态性的关联研究

目的 探讨一氧化氮合酶1(nitric oxide synthase 1,NOS1)基因多态性与精神分裂症易感性的相关性.方法 选取NOS1区域的28个标签单核苷酸多态性(single nucleotide polymorphisms,SNPs)位点,应用Illumina GoldenGate定制芯片对382例汉族精神分裂症患者和448名正常人的DNA进行分型,并分析其与精神分裂症的相关性.结果 单位点分析提示SNP位点rs1520811与精神分裂症存在关联,但是经过Bonferroni多重校正后差异无统计学意义(P＞0.05).单体型分析未发现单体型与精神分裂症的相关性.结论 未证实NOS1为精神分裂症的易感基因.     

Association analysis of toll-like receptor 4 polymorphisms in Japanese primary biliary cirrhosis

Primary biliary cirrhosis (PBC) is characterized by portal inflammation and immune-mediated destruction of intrahepatic bile ducts that often result in liver failure. Toll-like receptor (TLR) 4 recognizes lipopolysaccharides of Gram-negative bacteria. Infectious agents have been suspected to play a crucial role in PBC pathogenesis since TLR4 expression was found in bile duct epithelial cells and periportal hepatocytes in liver tissues of PBC. To assess the potential contribution of TLR4 SNPs to the development of this disease, we genotyped five SNPs in TLR4 in 261 PBC patients and 359 controls using a TaqMan assay. No significant positive associations with either PBC susceptibility or progression were uncovered. These results indicate that TLR4 polymorphisms do not play a prominent role in the development of PBC in Japanese patients.     

PATZ1基因单核苷酸多态性与无精症的关系

目的 研究PATZ1基因的4个单核苷酸多态性(single nucleotide polymorphism,SNP)rs2240424、rs2057951、rs2240427和rs714909的多态性与无精症的关系.方法 用PCR-限制性片段长度多态性分析方法,在180例无精症患者和190名正常男性中对上述4个SNP位点的基因频率和基因型频率分布进行调查.结果 rs2057951位点的等位基因C(35.0%vs.27.6%,P=0.031)和带有等位基因C个体(CT+CC)(57.8%vs.46.3%,P=0.027)的频率在无精症患者显著高于正常男性.4种SNP的单倍型在两组人群中的分布差异有统计学意义(P=0.01),单倍型ACAC(11.1%vs.6.6%,P=0.029)和ACGC(11.2%vs.5.2%,P=0.003)在无精症患者中显著高于正常男性.结论 PTAZ1的rs2057951位点的等位基因C和单倍型ACAC和ACGC增加无精症的易感性,提示PTAZ1基因可能与无精症发病相关.     

Transfer of alopecia areata in the human scalp graft/Prkdc(scid) (SCID) mouse system is characterized by a TH1 response

Alopecia areata is an autoimmune condition directed at hair follicles, which results in loss of hair. We have previously demonstrated that it is possible to transfer hair loss, along with the immunohistologic findings of alopecia areata, to human scalp grafts on Prkdc(scid) (SCID) mice by injection of autologous activated lesional T-cells. This study examines the cytokine profile of T-cells and follicular epithelium following transfer of hair loss. Two consistent findings significantly (P < 0.01) associated with hair loss were production of interferon-gamma-inducible protein-10 kDa (IP-10) by follicular epithelium (13/13), and production of INF-gamma by infiltrating T-cells (10/12). Noninjected control grafts regrew hair, and were generally negative for IP-10 (positive 2/9), and INF-gamma (positive 2/9), but expressed of IL-10 on the follicular epithelium (7/9). These data support an INF-gamma TH1 pathogenesis for hair loss in alopecia areata.     

TNFA基因启动子区多态性与HBV感染结局的关联研究

目的 在中国汉族人群中探讨TNFA基因启动子区单核苷酸多态性是否与HBV感染结局相关联。方法 以148例HBV自限性感染者和207例慢性乙肝患者为研究对象，应用聚合酶链反应-限制性片段长度多态性和序列特异性引物-PCR方法对TNFA基因启动子区5个位点，-238G／A、-308G／A、-857C／T、-863C／A和-1031T／C进行基因型分型，用EPI和EH等统计学软件分析各位点等位基因、基因型、单倍型频率及其组问差异。结果 TNFA基因-238位GG基因型在慢性肝炎组的频率显著高于自限性感染组（P=0．02），-857TT基因型的频率在慢性肝炎组显著低于自限性感染组（P=0.02）。TNFA基因-238／-308／-857／-863／-1031组成的单倍型GGCCT的频率在慢性肝炎组显著低于自限性感染组（P=0．03），单倍型GGcAT与GGTAT在慢性肝炎组的频率显著高于自限性感染组（P=0．0001，P=0．004）。结论 TNFA基因启动子区多态性与HBV感染结局显著关联。     

Association study of mast cell chymase polymorphisms with atopy

BACKGROUND: Atopic disorders are the result of complex interactions between genetic and environmental factors. Associations analyses between the promoter polymorphism rs1800875 in the mast cell chymase gene (CMA1) and atopy-related phenotypes have yielded inconsistent results. METHODS: We sequenced the CMA1 locus in 24 unrelated healthy individuals with serum IgE levels <50% percentile and 24 individuals with atopic eczema and serum IgE levels >90% percentile. Seven CMA1 single nucleotide polymorphisms (SNPs) were evaluated for evidence of associations with atopic phenotypes within a large population of German adults (n = 1875). Subjects were phenotyped by standardized questionnaires and interviews, skin prick testing and serum IgE measurements. Genotyping was performed using MALDI-TOF MS (Matrix-Assisted Laser Desorption Ionization-Time of Flight mass spectrometry). RESULTS: Promoter polymorphism rs1800875 was significantly associated with atopic eczema. No associations between any other single SNP and atopic phenotypes could be detected. Haplotype reconstruction revealed four of 128 possible haplotypes reaching estimated frequencies of 3% or more. Two of these haplotypes showed a borderline-significant association with atopic eczema, which did not remain significant after correction for multiple testing. CONCLUSIONS: Results confirm previous observations of a significant association between the CMA1 promoter polymorphism rs1800875 and atopic eczema, but not with serum IgE levels, and support the hypothesis that CMA1 serves as candidate gene for atopic eczema.     

Genetic variant association of PTPN22, CTLA4, IL2RA,as well as HLA frequencies in susceptibility to alopecia areata

ABSTRACT

Alopecia areata (AA) is characterized by a genetically complex inheritance. HLA frequencies, as well as the single nucleotide polymorphism (SNP) in PTPN22, CTLA4, and IL2RA genes, have been described to be associated with AA susceptibility. So far, no independent replication of these studies has been reported, and no data exist on a possible association between AA disease and these SNPs or influence of HLA frequencies in Iranian population. A possible association between HLA-DRB1*11 alleles as well as a single variation in PTPN22, CTLA4, and IL2RA genes and patchy AA disease have been investigated in a cohort from Iran. Patient and control subjects were genotyped for PTPN22 (rs2476601), CTLA4 (rs3087243), and IL2RA (rs3118470) variations as well as HLA frequencies. Gene expression levels were analyzed by real-time RT-PCR. In contrast to PTPN22 and CTLA4 gene polymorphisms, a significant association was found between IL2RA SNP and susceptibility to AA in Iranian cohort. While gene expression levels of IL2RA and PTPN22 were higher in the patients than that of controls, CTLA4 expression levels found significantly lower in the patients. Despite a significant association between AA and HLA-DRB1*11 frequencies, the presence of DRB1*11 is not associated with PTPN22, CTLA4, or IL2RA gene SNPs. Although the minor allele in IL2RA SNP can be a significant determinant of AA disease development in Iranian population, reported an association between the PTPN22 and CTLA4 variations was not confirmed by our study. Furthermore, these genetic risk factors might act independently from HLA alleles.     

Association between GOLGB1 tag‐polymorphisms and nonsyndromic cleft palate only in the Brazilian population

Nonsyndromic oral clefts are common congenital birth defects that exhibit variable prevalence around the world, often influenced by population‐dependent genetic predisposition. Few studies have been performed with nonsyndromic cleft palate only (NSCPO), limiting the knowledge of the genetic risk factors related to this type of oral cleft. Genetic variants in golgin subfamily B member 1 (GOLGB1), a gene that is essential for normal murine palatogenesis, were analyzed in this study to establish its potential association with NSCPO risk in the Brazilian population. Five tag‐single nucleotide polymorphisms (SNPs) of GOLGB1 (rs1169, rs7153, rs9968051, rs9819530, and rs6794341), which capture the majority of alleles spanning within gene, were genotyped in a case–control study with 270 patients with NSCPO and 284 unrelated healthy controls. The samples were also genotyped for 40 biallelic polymorphic markers to characterize the genetic ancestry. After adjustment for co‐variants, the GOLGB1 tag‐SNPs and the haplotypes formed by those SNPs were not significantly associated with NSCPO in this Brazilian case–control cohort. Our results suggest that common polymorphisms of GOLGB1 are not associated NSCPO susceptibility in the Brazilian population.     

ESR1基因单核苷酸多态性及单倍型与精神分裂症的关联研究

目的 探索雌激素受体1 (estrogen receptor 1,ESR1)基因rs2234693、rs9340799和rs3798759位点单核苷酸多念性(single nucleotide polymorphisms,SNPs)及其单倍型与精神分裂症(schizophrenia,SZ)发病之间的相关性.方法 应用聚合酶链反应-限制性片段长度多态性技术对333例SZ患者和315名正常对照rs2234693、rs9340799和rs3798759位点进行基因分型,应用x2检验对SZ组和对照组等位基因、基因型和单倍型频率进行分析.结果 rs2234693、rs9340799位点两组间基因型频率及等位基因分布差异均无统计学意义(P＞0.05).SZ组rs3798759位点GG基因型频率及G等位基因频率均高于健康对照组(P＜0.01).性别分层分析提示,女性SZ患者rs3798759位点TG、GG基因型频率及G等位基因频率均高于健康女性(P＜0.05).单倍型C-A-G和C-G-G在SZ组的分布频率高于对照组(P＜0.05).结论 rs3798759位点突变可能为女性精神分裂症发生的风险因子,C-A-G和C-G-G单倍型可能为精神分裂症的遗传风险单倍型.     

Familial alopecia areata: No linkage with HLA

HLA antigens of two Jewish families with alopecia areata were studied. There was no linkage between the disease and the HLA complex.     

Allograft inflammatory factor-1 and tumor necrosis factor single nucleotide polymorphisms in systemic sclerosis

Tumor necrosis factor (TNF) alleles have been associated with systemic sclerosis (SSc); however, these alleles may be in linkage with other genes. Allograft inflammatory factor-1 (AIF-1) is a newly identified gene on the short arm of chromosome 6 in the class III region of the human leukocyte antigen. It appears to be involved in inflammation and was originally identified in rat cardiac allografts undergoing rejection. AIF-1 has several sequence variations (single nucleotide polymorphisms, SNPs), three of which result in nonsynonymous changes in amino acid coding. We analyzed the linkage of five TNFA and five AIF-1 SNPs by polymerase chain reaction in 239 Caucasian individuals. The TNFA-1031T/T genotype was found to be associated with SSc (P < 0.0001) and both the DcSSc (diffuse subset of SSc) and the LcSSc (limited subset of SSc) subsets (P= 0.0004 and P= 0.0009, respectively) and the TNFA-237G/G genotype was found to be associated with all SSc (P= 0.0003) and with the DcSSc and LcSSc subsets (P= 0.01 and P= 0.005, respectively). Furthermore, the TNFA-857C/T genotype was associated with LcSSc (P= 0.0003) and TNFA-307A/A genotype associated with DcSSc (P= 0.028). In AIF-1, RS2269475 exon 4A allele, which generates a nonsynonymous change (tryptophan to arginine), was significantly associated in patients with SSc (P= 0.0009) and was associated with those patients who had DcSSc (P= 0.002). A strong linkage disequilibrium was observed between the AIF-1 alleles, A allele of RS2269475 and the A allele of RS4711274 (P < 0.0001), and linkage was observed between AIF-1 and TNFA alleles. Here, we report a novel and significant association of a nonsynonymous change within the AIF-1 with SSc and identified the linkage with TNFA alleles within 50 kb of this gene. Our study lends support that TNFA may be an important inflammatory modulator in SSc and may play a significant role with AIF-1 in disease pathogenesis.     

HTRA1基因单核苷酸多态性与类风湿性关节炎的关联性研究

目的 探讨HTRA1基因单核苷酸多态性(single nucleotide polymorphisms,SNPs)和类风湿性关节炎(rheumatoid arthritis,RA)及其患者血清类风湿因子(rheumatoid factor,RF)、C反应蛋白((C-reactive protein, CRP)之间的相关性.方法 采用Snapshot法测定344例RA患者和288名正常健康人HTRA1基因5个SNPs(rs2014307、rs2248799、rs2300433、rs714816、rs2268356)位点基因型,终点散射比浊法测定RA患者血清RF和CRP水平.结果 RA组HTRA1基因SNPs(rs2014307、rs2248799、rs2300433、rs714816、rs2268356)基因型与正常对照组间差异均无统计学意义(P>0.05),单倍型分析也显示H豫A1基因RA组与正常对照组间差异无统计学意义(P>0.05),RA患者HTRA1基闪SNPs位点(rs2014307、rs2248799、rs714816、rs2268356)不同基因型之间血清RF水平比较差异无统计学意义(P>0.05),而rs2300433位点基因型(AA+AG)组的RF水平明显高于GG组((P<0.05).结论 已分析的与HTRA1基因相关的5个SNPs与中国汉族人种RA遗传易感性不相关,HTRA1基因rs2300433位点不同基因型RA患者体内RF水平有差别,HTRA1基因表达的丝氨酸蛋白酶可能参与了RA患者RF的表达.