用染色体候选区域限定策略对诏安地区人群哮喘易感性的初

目的 对福建诏安地区哮喘感基因进行研究,以获得相关位点的资料,确定哮喘易感性与该区域的连锁关系。方法 用ＰＣＲ／ＲｓａＩ酶解检测位于染色体１１ｑ１３区的β链ＩｇＥ高亲和力受体基因（ＦｃεＲＩ－β）非编码区的两个多态性位点;用同位素掺入的ＰＣＲ法扩增位于染色体５ｑ３１－３３区的Ｄ５Ｓ４３６和Ｄ５Ｓ３９３多态性标记,对３２个哮喘家系,共１９２份样品进行分析。结果 ＦｃεＲＩ－β基因第２内含子区ＲｓａＩ     

支气管哮喘易感区域5q31-33内Tim-3基因单体型分析

目的： 探讨染色体上支气管哮喘易感区域5q31-33内Tim-3基因多态性与支气管哮喘的关系。方法：应用限制性片段长度多态性技术方法,分析了118个儿童变应性哮喘核心家系Tim-3基因4个SNPs(rs10053538、rs10515746、rs13170556和rs9313441)的基因型;采用基于家系传递不平衡检验（TDT）,分析基因分型数据;应用TRANSMIT软件构建单体型并进行单体型关联分析。结果：①基于家系的TDT分析显示,Tim-3基因的4个SNPs由杂合子父母传递给患病子代的等位基因频率不比预期值高,与哮喘无关（P>0.05）。②Transmit多个位点单体型分析结果显示由Tim-3基因rs10053538、 rs13170556、 rs9313441构建的单体型与支气管哮喘有关联（Global 2=10.83,P<0.05）。父母传递给患病子女GGG单体型的观察值小于期望值,差异显著（2=8.24,P<0.01）。结论：中国汉族人群中,位于染色体5q31-33区域的Tim-3基因本身或其附近的基因可能与儿童变应性哮喘的易感性相关。     

TAP1基因和FcεRIβ基因多态性与哮喘及其表型的相关性研究

目的：为研究TAP1基因和FcεRIβ基因多态性与哮喘及其表型的关系。方法：选择TAP1基因中微卫星DNA标志-TAP1及FcεRIβ基因中RFLP位点-RsaI,采用Amp-FLP和RFLP方法在散哮喘病人中进行分析。并检测其血清IgE水平,过敏原发皮试及气道高反应性,应用相关分析观察TAP1及RsaI等位基因与哮喘及其表型的关系。结果：RsaI位点等位基因片段与哮喘及气道高反应性相关,未见TAP1与哮喘或其表型相关。结论：FcεRIβ基因可能是哮喘发病的一个候选基因,TAP1基因可能与哮喘的发病无关。     

江浙沪地区HLA-DQB1基因对重症肌无力的遗传易感性研究

探讨中国汉人ＭＧ易感性与ＨＬＡ－ＤＱＢ１基因多态性的相关。方法：运用ＰＣＲ－ＲＦＬＰ法进行ＨＬＡ－ＤＱＢ１基因分型。结果：ＭＧ病例组与对照组比较都有ＤＱＢ＊０３０３频率的明显增高,ＤＱＢ＊０６０１和ＤＱＢ１＊０．６０２频率的明显降低,差异都有显著性。结论：ＤＱＢ１＊０３０３参与中国汉人ＭＧ的易感性,而ＤＱＢ１＊０６０１和ＤＱＢ１＊０６０２是保护基因。     

IgE高亲和力受体β链基因多态性与湖北汉族人变应性哮喘易感性的研究

目的探讨IgE高亲和力受体β链( high-affinity IgE receptor β gene, Fc ε RI β)基因启动子-109位C/T和编码区Glu237Gly基因多态性与湖北汉族人变应性哮喘易感性及血浆总IgE的关系. 方法采用聚合酶链反应-限制性片段长度多态性技术检测 Fc ε RI β基因启动子区-109位和编码区Glu237Gly两位点多态性,采用病例-对照法研究了216例变应性哮喘患者和198名对照. 结果 (1)湖北汉族人变应性哮喘患者 Fc ε RI β基因启动子区-109位T/T、T/C和C/C基因型频率是0.403、0.491和0.106;与对照相比差异无显著性(χ2=0.384,P＞0.05),但变应性哮喘组T/T基因型患者血浆总IgE对数值(2.539±0.8325)与T/C基因型的对数值(2.278±1.089)和C/C基因型的对数值(2.323±0.7852)相比差异具有显著性.(2)变应性哮喘患者 Fc ε RI β基因Glu237Gly位点Glu/Glu、Glu/Gly和Gly/Gly基因型频率为0.579、0.370和0.051,与正常对照相比差异具有显著性(χ2=13.62,P＜0.01),变应性哮喘患者Gly/Gly基因型血浆总IgE对数值为(2.622±0.9374),与Glu/Glu和Glu/Gly相比差异具有显著性. 结论 Fc ε RI β基因启动子区-109位T/T基因型与血浆总IgE高度相关,编码区237位Gly/Gly基因型与中国湖北汉族人变应性哮喘及血浆高IgE相关.     

5-羟色胺转运体基因多态性与支气管哮喘及抑郁症易感性的研究

目的 检测5-羟色胺转运体(5-hydroxytryptamine transporter,5-HTT)基因的两种多态性(5-HTTLPR及Stin2),以探讨哮喘合并抑郁症的分子遗传学机制.方法 收集成人哮喘患者156例,采用汉密尔顿抑郁量表(Hamilton depression scale,HAMD)进行抑郁评分,将哮喘组分为哮喘合并抑郁组(HAMD≥8分)和单纯哮喘组(HAMD<8分).另设立两组对照,即抑郁症组(n=508)和健康对照组(n=433).采集所有受试者外周血,应用聚合酶链反应方法,扩增包括5-HTTLPR或Stin2多态区域的5-HTT基因片段,在琼脂糖凝胶电泳后使用全自动凝胶数码成像及分析系统分析扩增目的 基因片段.结果 Stin2多态性的基因型频率分布和等位基因频率分布显示,具有Stin2.12/Stin2.10基因型或Stin2.10等位基因型的男性发生哮喘的风险明显增加(Stin2.12/Stin2.10:OR=2.291,95%CI:1.195,4.390;Stin2.10:OR=1.942,95%CI:1.069-3.527),而5-HTTLPR的基因型和等位基因频率分布在哮喘(包括哮喘合并抑郁组和单纯哮喘组)或按性别分层的哮喘与健康对照之间的差异均无统计学意义(P均>0.05).结论 5-HTT基因Stin2多态位点可能在男性哮喘发病中发挥一定作用,该结果支持哮喘与抑郁之间可能存在一定遗传学发病机制相关性的假设.     

CDH1基因-160(C→A) 多态与福建地区中国人群胃癌遗传易感性的关联研究

目的 上皮钙黏着蛋白（E—cadherin）的编码基因CDHI是重要的肿瘤抑制基因，本研究探讨CDH1基因-160（C→A）多态性在福建地区胃癌人群中的分布及其与福建地区胃癌发病风险的相关性。方法 采用聚合酶链反应-变性高效液相色谱分析方法对102例胃癌患者和101名正常对照者进行CDH1基因-160（C→A）多态的基因型分析，比较基因型分布和发病风险的关系；危险度OR及95％CI应用非条件Logistic回归分析计算。结果 CDH1基因-160（C→A）多态的CC、CA、AA基因型在病例组中的分印频率分别为58（56．9％）．38（37．3％），6（5．9％）；在对照组的分布频率分别为55（54．5％），41（40．6％），5（5％）；两组间分布的差异无统计学意义（P〉0．05）。AA基因型没有显著性地提高或降低胃癌的发病危险（OR=1．12；95％CI：0．32～3．95）；携带A等化基因与胃癌的临床病理特征也无关联性。结论 CDH1基因-160（C→A）多态性可能与福建地区中国人群胃癌发生的遗传易感性无关。     

IL-4R、IL-13、ADAM33基因多态性与中国皖南地区汉族人群支气管哮喘的相关性研究

目的:探讨IL-4受体基因Arg551Gln(rs1801275)、IL-13基因Arg130Gln(rs20541)、ADAM33基因T1(rs2280091)位点基因多态性与中国皖南地区汉族人群支气管哮喘的相关性。方法:采用病例-对照的方法,用聚合酶链反应及直接基因测序法比较116例支气管哮喘组与70例正常人对照组之间基因型、等位基因频率的差异。结果:哮喘组和对照组IL-4受体基因Arg551Gln位点和IL-13基因Arg130Gln位点的基因型和等位基因型频率的差异有统计学意义,ADAM33基因T1位点基因型哮喘组和对照组差异有统计学意义,等位基因型频率在哮喘组和对照组差异无统计学意义。结论:提示IL-4R Arg551Gln(rs1801275)位和IL-13基因Arg130Gln(rs20541)位的多态性可能与中国皖南地区汉族哮喘有相关性;ADAM33基因(rs2280091)T1位点位的多态性可能与中国皖南地区汉族哮喘无相关性。     

IL-10基因启动子多态性与皖南地区汉族人群支气管哮喘的相关性研究

目的:探讨IL-10基因启动子-1082G/A(rs1800896)、-819C/T(rs1800871)、-592C/A(rs1800872)位点多态性与安徽皖南地区汉族人群支气管哮喘的相关性。方法:采用病例-对照方法,用聚合酶链反应及直接基因测序法比较183例支气管哮喘组与151例正常人对照组之间基因型、等位基因频率的差异。结果:哮喘组IL-10基因启动子-1082G/A、-592C/A位点基因型与对照组相比有差异(P<0.05),其等位基因型频率在哮喘组和对照组间亦有差异(P<0.05)。而-819C/T位点基因型及等位基因型频率在哮喘组和对照组间均无差异(P>0.05)。结论:IL-10基因启动子rs1800896(-1082G/A)位点和rs1800872(-592C/A)位点的多态性可能与安徽皖南地区汉族哮喘相关;而rs1800871(-819C/T)位点的多态性可能与安徽皖南地区汉族哮喘无相关。     

TIM-4基因多态性与湖北地区汉族人群支气管哮喘易感性的研究

目的 探讨T细胞免疫球蛋白域及黏蛋白域蛋白-4(T cells immunoglobulindomain andmucindomain protein-4,TIM-4)基因外显子2区Lys65Lys(G/A)、外显子9区Val1365Met(G/A)的单核昔酸多态性(SNP)与湖北地区汉族人群支气管哮喘易感性的关系.方法 采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)的方法对湖北地区185例哮喘患者和162例健康者TIM-4基因外显子2区Lys65Lys(G/A)、外显子9区Vai365Met(G/A)的多态性进行分析,计算基因型和等位基因频率.结果 (1)湖北地区汉族人群健康者TIM-4基因外显子2区Lys65Lys(G/A)位G/G、G/A、A/A基因型频率分别为0.840、0.160、0,而哮喘人群其频率分别为0.859、0.141、0,其基因型和等位基因型频率与对照组相比差异均无统计学意义(P=0.603,P=0.618);(2)本试验未检测到TIM-4外显子9区Va1365Met(G/A)的多态性.结论 湖北地区汉族人群TIM-4基因外显子2区Lys65Lys(G/A)存在单核苷酸多态性变异,但该位点的变异与湖北地区汉族人群支气管哮喘易感性无关;TIM-4基因外显子9区Va1365Met(G/A)在湖北地区汉族人群中未发现单核苷酸多态性.     

β2-肾上腺素能受体基因的多态性与哮喘及其临床表型的关系

目的 探讨β2－肾上腺素能受体（β2-adrenergic receptor,β2AR）基因的多态性与中国人哮喘易感性的连锁关系，以及对疾病调节作用的重要性。方法 用聚合酶链反应－限制性片段长度多态性技术，检测β2AR基因编码区第16、27、164位氨基酸变异位点及核苷酸523（C－A）位点，对166例哮喘患儿及32个哮喘家系共192份样品进行了分析。结果 所获得的中国人β2AR基因多态性位点的等位基因频率，除编码区Thr164Ile位点的频率与白种人基本相同外，其余3个位点的等位基因频率与白种人明显不同，差异有显著性（P＜0.01）。未能获得β2AR基因多态性位点与哮喘、血清总IgE、变应原皮肤点刺实验阳性数，以及肺功能（1秒用力呼气流量和最大峰流速）具有相关性的肯定结果，未能证实Arg16Gly和Gln27Glu两位点的不同基因型与哮喘患儿吸入β2AR激动剂后气道反应性的调节有关。结论 本研究的两组样本中，未能证实β2AR基因多态性是哮喘易感性、并参与调节哮喘临床表型的主要遗传决定基因。     

The effect of galectin-3 genetic variants on the susceptibility and prognosis of gliomas in a Chinese population

The aim of this study is to explore the association between the polymorphisms of galectin-3 gene and clinico-pathological characteristics and prognosis of gliomas. We enrolled 190 histologically diagnosed gliomas and 210 healthy controls in this study. Two genetic variants at galectin-3 single nucleotide polymorphism (SNP) sites (galectin-3 +191 A>C and +292 A>C) were determined. We found that the A/A genotype at galectin-3 gene +292 A>C was significantly more prevalent in gliomas patient than in controls (42.1% vs. 29.0%, P = 0.021); the A allele frequency was markedly higher in gliomas subjects than in controls (61.8% vs. 45.0%, P = 0.008). There was a markedly higher prevalence of AA carriers in high-grade subgroup than in low-grade subgroup (50.5% vs. 31.8%, P = 0.012). The Kaplan–Meier analyses showed that the gliomas patients carrying AA genotype of galectin-3 gene +292 A>C had marked shorter overall survival period than those did not (AA vs. AC+CC, 22.2 ± 3.8 months vs. 38.3 months ± 7.9; P = 0.04). The SNPs at +191 A>C of galectin-3 gene did not show positive association with clinico-pathological characteristics and prognosis of gliomas. The results of this study suggest the SNPs at +292 A>C, not SNPs at +191 A>C, of galectin-3 gene were associated with the tumor grade and prognosis of gliomas.     

Association of genetic polymorphisms on BTNL2 with susceptibility to and prognosis of dilated cardiomyopathy in a Chinese population

Background: Dilated cardiomyopathy (DCM) is one type of primary myocardial disease, partly caused by immunity dysfunctions. BTNL2 (butyrophilin-like 2) has already been confirmed to be involved in the etiology of autoimmune disorders and GWAS (genome wide association study) has also identified mutants of a SNP (single nucleotide polymorphism) near BTNL2 could modulate risk of coronary heart disease (also cardiomyopathy). The current study, therefore, was aimed to investigate whether polymorphisms within or around BTNL2 would be correlated with susceptibility to and prognosis of DCM. Material and methods: Peripheral blood samples were gathered from 82 DCM patients and 75 healthy controls. Nine tag-SNPs within or near BTNL2 were obtained from HapMap Database and previously published studies. Eligible haplotypes were gained on the basis of SHesis software. Genotyping of SNPs was implemented with aid of Sequenom MassArray iPLEX platform and subsequently analyzed via MALDI-TOF mass spectrometry. The odd ratios and their 95% confidence interval (95% CI) were utilized to evaluate the correlations between SNPs/haplotypes and DCM risks. Finally, Cox proportional hazard models and Kaplan-Meier curves were performed to assess association of SNPs/haplotypes with prognosis of DCM patients. The statistical analyses were conducted with SPSS 19.0 software. Results: Under the allelic model, rs3763313 (A > C), rs9268494 (C > A), rs9268492 (C > G) and rs9268402 (A > G) were remarkably associated with susceptibility to grade IV of DCM classified by NYHA (New York heart association) (OR = 0.43, 95% CI: 0.22-0.84; P = 0.018; OR = 0.49, 95% CI: 0.27-0.91; P = 0.024; OR = 0.50, 95% CI: 0.27-0.94; P = 0.035; OR = 0.53, 95% CI: 0.28-0.97; P = 0.048). Haplotype C-C-A-T (rs9268492, rs9268494, rs3763313 and rs3763317 synthesized) was also regarded as a protective factor for DCM patients compared with carriers of other haplotypes (OR = 0.50, 95% CI: 0.26-0.97, P = 0.038). Moreover, the univariate survival analysis and multivariate Cox regression analysis both indicated noticeable correlations between rs9268402 and haplotype C-C-A-T and prognosis of DCM patients (NYHA IV), respectively (Long-Rank P = 0.029, HR: 0.241, 95% CI: 0.089-0.650, P = 0.005; Long-Rank P = 0.036; HR = 0.126, 95% CI: 0.035-0.457, P = 0.002). Nonetheless, rs3763313 was found only associated with prognosis of DCM patients (NYHA IV) expressed in the Kaplan-Meier curve (P = 0.009). Conclusion: The genetic mutations within or around BTNL2 (rs3763313, rs9268494, rs9268492 and rs9268402) could alter susceptibility to grade IV of DCM in a Chinese population, and the 2 SNPs (rs3763313 and rs9268402) therein added with haplotype C-C-A-T might separately predict the prognosis of DCM patients. However, additional studies regarding diverse ethnicities need to be furthered to validate our results.     

Ethnic differences in genetic susceptibility to atopy and asthma

The genetics of asthma and atopy is complex, but can be approached by studies of both candidate genes and mapping of susceptibility loci. Genetic factors conferring susceptibility to disease may vary among ethnic groups. We present our experience with some candidate gene studies for asthma and atopy and susceptibility locus mapping for linkage to chromosome 5q.     

ADAM33 polymorphisms are associated with asthma susceptibility in a Japanese population

BACKGROUND: Asthma is the most common chronic disorder in childhood, and asthma exacerbation is an important cause of childhood morbidity and hospitalization. Asthma is believed to be a complex disorder involving genetic and environmental factors, and several asthma susceptibility loci have been identified through genome-wide screening. A disintegrin and metalloprotease 33 (ADAM33) was the first asthma susceptibility gene to be discovered by positional cloning in 2002. OBJECTIVE: The aim of the present study was to investigate whether single-nucleotide polymorphisms (SNPs) in ADAM33 are associated with childhood asthma in the Japanese population. METHODS: Twenty-three ADAM33 SNPs were genotyped by fluorescence correlation spectroscopy with the use of DNA from 155 families (538 members) identified through children with atopic asthma. The transmission disequilibrium test (TDT) was performed for family-based association study. RESULTS: TDT revealed that minor alleles of S+1, ST+4, and T2 SNPs were over-transmitted to asthma-affected offspring (P<0.05). According to the haplotype TDT, no haplotype of ADAM33 was transmitted preferentially to asthmatic offspring. CONCLUSION: Our results confirm the involvement of ADAM33 in the development of childhood asthma among the Japanese.     

Interleukin-17A and -17F single nucleotide polymorphisms associate with susceptibility of asthma in Chinese Han population

Interleukin 17 (IL-17) plays important roles in the progression of asthma. Genetic variants in the Il-17 may influence the immunopathogenesis of many diseases. Many studies have investigated the relevance of IL-17 polymorphism with cancers or immune diseases, including asthma. In this study, single nucleotide polymorphisms (SNPs) of IL-17 were explored by PCR-RFLP and verified by sequencing method. The frequencies of genotypes and alleles were analyzed. Haplotypes were analyzed with the SHEsis online program. The relationship between the genotypes of SNPs and IgE level was also investigated. The False Discovery Rate (FDR) correction was performed (P-adjusted?<?0.05). The frequencies of A allele, GA and (GA?+?AA) genotype of rs3748067 were significantly higher in asthma patients. As for rs763780, the C allele in patients was more frequent than healthy controls. In addition, we found C carriers (CT?+?CC) were significantly higher in asthma patients. We further found that the haplotype CT for IL-17F (rs763780/rs2397084) was associated with an increased susceptibility of asthma, but this association did not survive after FDR correction. The level of serum total IgE in mutant group (GA?+?AA) of rs3748067 was significantly higher than the wild genotype (GG) group and control group. These results suggested that IL-17 SNPs, but not haplotypes may be associated with the susceptibility of asthma in Chinese Han population from central China.