HLA-DRB1基因与慢性荨麻疹的相关性

目的探讨慢性荨麻疹与HLA-DRB1等位基因的相关性。方法采用聚合酶链反应-序列特异性引物方法,检测慢性荨麻疹(CU)患者组144例(汉族64例,壮族80例)和正常对照组199例(汉族95例,壮族104例)的HLA-DRB1等位基因频率,使用SPSS13.0统计软件分析。结果在检测的16个位点中,DRB1*12和*1401等位基因频率在汉族患者组与汉族对照组间差异有统计学意义(Pc<0.001,RR=6.715;Pc<0.001,RR=28.776);DRB1*1401等位基因频率在壮族患者组与壮族对照组间差异有统计学意义(Pc=0.002,RR=4.526)。DRB1*12等位基因频率在汉族患者组与壮族患者组间比较,差异有统计学意义(Pc<0.001)。结论 DRB1*12和*1401等位基因可能与汉族CU有相关性;DRB1*1401等位基因可能与壮族CU有相关性;DRB1基因多态性在汉、壮族间分布有差异。     

Human Leukocyte Antigen-A,-B,-C and -DR Alleles and Soluble Human Leukocyte Antigen Class I Serum Level in Ménière's Disease

Previous studies have suggested that many human leukocyte antigen (HLA)-A,-B,-C and -DR alleles are associated with Ménière's disease (MD), an inner ear disorder with a proposed autoimmune etiopathogenesis. Despite some discrepancies many reports are in agreement with a hypothesis suggesting an influence of serologically detected HLA-C products in the susceptibility to the disease. To confirm these data we investigated the distribution of HLA-A,-B,-C and-DR antigens that well define the HLA polymorphism using DNA typing. Furthermore, as autoimmune factors have been claimed to play a role in MD, we investigated the serum level of soluble HLA class I (sHLA-I). Molecular typing of HLA class I and II was performed using polymerase chain reaction sequence-specific primers in 41 patients affected by MD, 34 patients affected by other inner ear diseases (OIDs) and 101 healthy subjects. An ELISA technique was employed to investigate the serum level of sHLA-I in 17 MD patients, 10 OID patients and 83 healthy subjects. The results showed a significantly increased frequency of the Cw*07 specificities in MD patients when compared to OID patients (63.4% vs 32.3%; p =6.9 &#50 10 -3 ; relative risk [RR]=3.6) and healthy subjects (63.4% vs 35.6%; p =2.28 &#50 10 -3 ; RR =3.1). The sHLA-I concentrations detected in sera did not differ significantly between MD patients (616 &#45 271 ng/ml), OID patients (570 &#45 307 ng/ml) and healthy subjects (518 &#45 340 ng/ml).     

X-连锁迟发性脊椎骨骺发育不良的基因诊断研究

目的 探讨应用连锁分析和基因测序方法对X-连锁迟发性脊椎骨骺发育不良(Xinked spondylepiphyseal dysplasia tarda,SEDL)进行基因诊断的可行性。方法 利用与SEDL基因毗邻的微卫星遗传标记DXSl6多态性对一个SEDL大家系的21名成员进行连锁分析,确定与该家系SEDL致病基因连锁的DXSl6等位基因型,对家系中的年轻女性和年幼男性进行基因诊断。为探讨连锁分析诊断的准确性,随后对SEDL基因编码外显子3—6进行PCR扩增产物双向直接测序以确定导致该家系发病的SEDL基因突变型,通过检测致病基因对待诊对象进行直接诊断。结果 21名家系成员的连锁分析结果显示与致病基因连锁的DXSl6是D2等位基因,6位待诊对象中IVt4、IVl9、IV21、V7各有一个DXSl6D2等位基因,表明她们是携带者;而IV23和V4不具有与致病基因连锁的DXSl6等位基因,表明她(他)们是正常人。对21名成员的DNA测序证实该家系的致病突变是首次发现的SEDL基因第2内含子剪接受体处IVS2-2A→C突变。待诊对象IVl4、IVl9、IV21、V7携带该突变,IV23和V4基因型正常。基因测序和连锁分析的诊断结果完全一致。结论 连锁分析用于SEDL基因诊断简便、快速、花费少、与基因测序方法一样准确,解决了长期以来SEDL症状前患者和潜在女性携带者无法诊断的难题,有重要的临床价值。     

白细胞介素8单核苷酸多态性与呼吸道合胞病毒易感性关联的研究

目的探讨白细胞介素8（IL-8）-251T／A和781C／T单核苷酸多态性（SNP）与呼吸道合胞病毒（RsV）易感性的关系。方法采用等位基因特异性聚合酶链反应（AS—PCR）技术,对101例RSV肺炎、108例非RSV肺炎住院患儿及35个核心家系的两个SNP位点的基因型进行检测,通过基因测序进行验证。用病例-对照和传递不平衡检验（TDT）分析SNP位点等位基因的分布,并对两个SNP位点的连锁和单体型进行分析。结果（1）病例组IL-8—251T的频率显著增加（OR=2．08,P=0．0002,病例-对照分析;LRT=14．31,P=0．0008,VDT）。（2）IL-8—251T与781C是连锁的（D’=0．607±0．03,r^2=0．2861,P=0．0000）。（3）病例组TC单体型的频率显著增加（P=0．01）。结论IL-8—251T与781C形成的TC单体型与RSV易感性存在关联,即部分RSV易感基因可能存在于含有TC单体型的基因片段中或者与该段基因紧密连锁。     

武汉汉族新生儿中肺表面活性物质蛋白D基因多态性及其与支气管肺发育不良相关性分析

目的: 研究武汉汉族新生儿中肺表面活性物质蛋白D(SP-D)基因多态性及其与支气管肺发育不良(BPD)易感性的相关关系。方法: 采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)对218例武汉汉族新生儿SP-D相关位点进行基因型检测,同时进行基因测序验证结果。结果: SP-D Met11Thr三种基因型TT、TC、CC频率分别为10.5%、49.1%、40.4%,等位基因T和C频率分别为35.1%和64.9%。SP-D Ala160Thr三种基因型GG、GA、AA频率分别为54.6%、39.4%、6.0%,等位基因G和A频率分别为74.3%和25.7%。与对照组比,SP-D Met11Thr和SP-D Ala160Thr基因多态性与BPD发生率无明显关联(P>0.05)。结论: SP-D Met11Thr和SP-D Ala160Thr基因型和等位基因频率存在种族差异性;SP-D Met11Thr和SP-D Ala160Thr基因多态性与BPD发生率无明显关联。     

Estimation of optimal donor number in Bone Marrow Donor Registry: Hong Kong’s experience

Better outcome for hematopoietic stem cell transplantation (HSCT) requires optimal matching between donor and recipient at the HLA-A, -B, -C, and -DRB1 loci. This study estimates the likelihood of identifying HLA matched donors in Hong Kong.7595 volunteer unrelated Chinese donors at the Hong Kong Bone Marrow Donor Registry were typed with HLA-A, -B, -C and -DRB1 genotypes. The matching probabilities for 8/8 and 7/8 HLA match via the matching models were determined.Based on current 100,000 donors in the HKBMDR, the matching probabilities are 45% at 8/8 HLA match and 65% at 7/8 match. By increasing the registry to 200,000, the likelihoods of match become 54% and 73% at 8/8 and 7/8 match stringencies respectively.Our findings may be helpful in planning future donor recruitment and HLA typing. A cost-effective Bone Marrow Donor Registry with a larger pool of donors could increase chance of matching and the success of HSCT.     

白细胞介素-1家族基因多态性与子宫内膜异位症的相关性研究

目的：探讨白细胞介素1（interleukin-1，IL-1）家族基因多态性与子宫内膜异位症（endometriosis，EMs）的相关性。方法：用聚合酶链式反应技术（PCR）及限制性片断长度多态性（RFLP），对138例EMs患者及100例对照者的IL-1β基因-511和＋3953位点及IL-1RA基因进行分析。结果：EMs组IL-1β-511位点的基因型（C／C、C／T、T／T）频率和等位基因（C、T）频率，IL-1β＋3953位点基因型（C／C、C／T）及等位基因（C、T）频率与对照组比较，差异均无显著性（P〉0．05）。IL-1RA基因型A1／A1、A1／A2、A1／A4、A2／A2频率在EMs组和对照组分别为84．1％、12．3％、2．9％、0．7％和95％、4％、1％、0％，两组比较P=0．042；A1、A2、A4等位基因频率在两组间分别为91．7％、6．9％、1．4％和97．5％、2％、0．5％，两者比较均具有显著性差异（P=0．019）。A1／A2基因型个体患EMs的危险性是野生型A1／A1纯合子的3．48倍（95％CI：1．13～10．69），携带A2等位基因者患EMs的危险性是携带A1等位基因的3．66倍（95％CI：1．23～10．94）。结论：IL-1β-511及＋3953位点的基因多态性与中国浙江籍汉族EMs患者的遗传易感性无关联，而IL-1RA基因的A2型等位基因可能是EMs的易感因素之一。     

Further sequence and length variation at the STR loci HumFES/FPS, HumVWA, HumFGA and D12S391

This paper reports population data and statistics for the HumFES/FPS, HumVWA, HumFGA and D12S391 loci in Austria. The sequences of some rare and new variant alleles which have been identified in the course of the present population study and other investigations are described. Sequence variation occurred in a HumFES/FPS allele revealing an (ATTT)₉ structure and an A to C transversion in the 5′ flanking region. At the HumVWA locus the structural type of the common allele 14 has been found in one allele 13 and in three examples of allele 15. Additionally the TCTA (TCTG)₃(TCTA)_n structure has been observed in three examples of allele 13 and one allele 14, which is very uncommon. Another allele 14 showed a C to T transition in the third of nine TCTA repeats. The sequences of three length variations at the HumFGA locus, namely the alleles 16, 19.2 and 21.2 are reported. At the D12S391 locus a novel 19.1 allele was found in this study. An extended nomenclature is proposed for the HumVWA locus to denominate sequence variants in a precise but simple way. Received: 14 October 1998 / Received in revised form: 18 February 1999     

组织相容性复合体-非经典基因与1型糖尿病临床状态相关性的研究

目的 研究组织相容性复合体-DMA、DMB基因与中国人1型糖尿病临床状态的相关性。方法 根据性别、发病年龄、起病急缓、起病时酮症发生情况、胰岛β细胞残存功能(就诊时空腹C-肽水平)等临床状态的不同,将1型糖尿病患儿进行分组,研究DM易感性基因和二聚体在不同临床状态分组中的频率分布情况。结果 (1)DMA*0103、DMB*0103基因在1型糖尿病患儿中的频率显著高于正常对照,分别为50．0％、4．0％,为1型糖尿病的易感性基因。DMA*0103／DMB*0103、DMA*0103／DMB*0104、DMA*0103／DMB*0101二聚体在1型糖尿病患儿中的频率也显著增高,分别为15％、24％、13％,为1型糖尿病的易感性二聚体。(2)携带DMB*0103基因或DM易感性二聚体的个体,在C—肽低水平患儿组中的频率均显著高于C-肽高水平组。DM易感性二聚体与患儿的发病年龄及发病时酮症发生情况也有显著的相关性,携带DM易感性二聚体的个体,10岁前发生糖尿病的概率显著增加,新发生1型糖尿病时也更易出现酮症或酮症酸中毒。结论 DM基因和二聚体均与1型糖尿病临床状态存在显著的相关性,1型糖尿病的临床状态异质性有一定的遗传机理起作用。