HLA-DPB1基因型与疾病相关性的研究进展

HLA基因型别与移植和疾病密切相关 ,其中HLA DPB1曾被认为与疾病最不具有相关性 ,而最近几年的报道却认为DPB1与许多疾病密切相关。就此本文阐述了HLA DPB1基因型别与几种疾病的相关性     

支气管哮喘HLA—DRB1等位基因研究

目的：研究山西汉族支气管哮喘患者的ＨＬＡ－ＤＲＢ１等位因基的频率。方法：采用顺序特异引物聚合酶链反应（ＰＣＲ／ＳＳＰ）技术检测山西汉族６４例支气管哮喘患者ＨＬＡ－ＤＲＢ１等位基因频率,并与山西正常人群进行比较分析。结果：支气管哮喘组ＨＬＡ－ＤＲＢ１＊１５０１／１５０２基在频率明显增高（Ｐ〈０．０５）,Ｏ ２３．４４％;其它等位基因频率在两组间无显著差异。结论：在山西汉族人群中ＨＬＡ－ＤＲＢ１＊１５     

南方汉族慢性髓细胞性白血病与HLA-DPB1 等位基因的相关性研究

为了探讨慢性髓细胞性白血病(CML)与人类白细胞抗原(HLA)DPB1基因的相关性和分析其遗传易感性，采用测序分型技术(SBT)对86例主要为广东籍的南方汉族CML患和82例健康对照进行HLA-DPB1基因分型。结果表明HLA-DPB1*1301和DPB1*20011的基因频率在病例组高于对照组。结论：这些等位基因与CML间可能存在正相关关系。     

四川骨髓库四川籍汉族人群MICA等位基因分布

目的研究四川骨髓库四川籍汉族志愿者MICA等位基因分布特点。方法采用PCR-SBT和PCR-SSP方法,对四川骨髓库119名无关汉族志愿者标本作MICA等位基因分型和MICA基因缺失型分析。结果共检测到13种已知MICA等位基因和2种新MICA等位基因,频率依次为MICA*010(25.2%)、MICA*008:01/04(23.1%)、MICA*002:01(16.0%)、MICA*019(10.5%)、MICA*012:01(8.8%)、MICA*049(4.2%)和MICA*009:01(3.8%),这7种等位基因占所有MICA等位基因的91.6%。与浙江汉族相比,仅MICA*027分布的差异有统计学意义(P<0.05);与内蒙古汉族、韩国人、美国白人及非洲裔美国人相比,MICA*004和MICA*019分布的差异有统计学意义(P<0.05)。所发现的3例2种MICA新等位基因,已被世界卫生组织HLA因子命名委员会分别命名为MICA*064N和MICA*010:02。连锁不平衡分析发现,四川骨髓库汉族人群中B*1301-MICA*045,B*4801-MICA*Del紧密连锁;最常见的4位点单体型是A*0207-B*4601-MICA*010-DRB1*0901。结论四川籍汉族人群MICA等位基因表现出较丰富的多态性,具有其自身的特点。     

HLA-DPB1基因型与疾病相关性的研究进展

HLA基因型别与移植和疾病密切相关，其中HLA-DPB1曾被认为与疾病最不具有相关性，而最近几年的报道却认为DPB1与许多疾病密切相关。就此本文阐述了HLA-DPB1基因型别与几种疾病的相关性。     

HLA-DRB1~*等位基因与肺结核的相关性研究

目的探讨人类白细胞抗原HLA-DRB1*等位基因与肺结核发病相关性,寻找与肺结核发病可能相关的HLA-DR易感基因。方法采用病例-对照的研究方法,用PCR-SSO分型技术对80名肺结核患者和105名健康对照者的HLA-DRB1基因分型,统计分析比较基因频率和相对危险率。结果肺结核病组中的HLA-DRB1*14频率明显高于对照组(10.63%vs3.81%),差异有显著性统计学意义(χ2=6.6955,P<0.05),相对危险率2.91。结论HLA-DRB1*14基因可能与肺结核的易感性相关。     

人类白细胞抗原-B等位基因与儿童支气管哮喘的研究

目的通过人类白细胞抗原(HLA)-B基因检测分析探讨广西地区范围哮喘儿童HLA-B等位基因遗传分布情况。方法将居住广西南宁地区无血缘关系的84例哮喘儿童和168例无哮喘和特应性疾病的健康个体为对照组纳入研究。采用Pharmacia UniCAP系统检测哮喘儿童的血清总IgE水平,同时完成10种吸入性过敏原皮肤实验和肺功能检查。应用基因芯片法检测HLA-B的27个等位基因位点。计算疾病组和对照组的基因频率=基因出现频次数/(每组个体总数×2)×100%,进行χ2检验和危险性分析。结果支气管哮喘组HLA-B56等位基因和HLA-B58等位基因频率(分别为5.36%和14.28%)明显高于健康对照组(分别为0.89%和8.04%),(χ2值为7.973,P<0.01和5.421,P<0.05),比值比(OR)分别为6.6(95%可信限1.737~25.076)和2.09(95%可信限1.115~3.912);而HLA-B46等位基因和HLA-B61等位基因频率在哮喘组(分别为6.55%和1.19%)低于对照组(分别为12.80%和4.76%),(χ2值为5.197和4.308,P<0.05),OR分别为0.438(95%可信限0.213~0.902)和0.232(95%可信限0.055~1.100)。结论HLA-B56等位基因和HLA-B58等位基因与广西南宁地区哮喘儿童易感性相关;HLA-B46等位基因对机体则可能有保护性。     

自身免疫性肝病与HLA-DRB1等位基因相关性研究

目的通过检测人类白细胞抗原(HLA)Ⅱ类等位基因DRB1*0401～*0408,分析基因频率与临床表现的关系,初步探讨HLA-DRB1多态性与自身免疫性肝炎和原发性胆汁性肝硬化的相关性。方法按自身免疫性肝炎和原发性胆汁性肝硬化的诊断标准筛选病例。以31例江苏地区汉族人自身免疫性肝病患者(自身免疫性肝炎12例,原发性胆汁性肝硬化19例)为研究对象,以42例健康人为对照组。采集静脉血,用酚-氯仿法提取全血DNA。用序列特异性引物聚合酶链反应(PCR- SSP)技术检测HLA-DRB1*0401～*0408等位基因频率。结果自身免疫性肝病患者HLA-DRB1*0404等位基因的频率(35.5%)明显高于健康人(7.1%),RR为7.15,(P<0.005),其他各等位基因频率在2组间虽有不同,但无统计学意义的显著性差异。自身免疫性肝炎组和原发性胆汁性肝硬化组之间HLA-DRB1*0404及其他各等位基因频率无统计学意义的显著性差异。结论HLA-DRB1*0404等位基因可能与自身免疫性肝病的发生有关联。     

直接测序法用于四川骨髓库汉族人群HLA-C等位基因分布的研究

目的建立HLA-C等位基因通用引物直接测序法,研究中华骨髓库四川分库(简称四川骨髓库)中川籍汉族人群HLA-C等位基因分布。方法在四川骨髓库已获HLA-A/B/DRB1高分辨分型结果的600余份川籍汉族街头无关自愿捐献者标本中,随机选择244份标本,采用PCR-SBT对HLA-C位点测序分型,通用引物测序后产生的模棱两可分型结果,分别采用加测相应外显子和组特异性测序方法确认;获得所有标本确切的高分结果后,计算HLA-C各等位基因分布频率,并与其他人群比较。结果 244份标本中直接出HLA-C位点高分辨结果的比例为27.87%(68/244),须加测外显子1、5、6和7的为61.07%(149/244),须组特异性测序的为47.54%(116/244);共检出HLA-C等位基因25个,其中等位基因频率>10%的3个:C*01∶02、C*07∶02和C*03∶04,等位基因频率>1%的12个,累计频率95.69%;四川汉族人群HLA-C等位基因的分布与中国南方人群最为接近,与美国高加索人群和黑人的差异最大。另外,发现了1例新等位基因C*06∶45,它与同源性最高的C*06∶02在第187位碱基存在1个点突变:G>T,使密码子39由GAC>TAC,导致编码的氨基酸由天门冬氨酸(Asp)>酪氨酸(Tyr);此位点在此之前尚未发现过碱基突变。结论建立了针对HLA-C基因第2—4外显子的通用引物直接测序法,并提出了模棱两可结果的解决策略,所测标本均获得确切高分结果;四川汉族人群中HLA-C等位基因呈现多样性并存在自身特点。     

STAT6基因3’非翻译区G2964A位点多态性与湖北汉族哮喘人群及IgE的相关性研究

目的　研究信号转导和转录激活因子 (STAT) 6基因 3′非翻译区G2 96 4A位点多态性与湖北汉族人群哮喘的易感性及血浆IgE水平的关系。方法　用聚合酶链反应和限制性片段长度多态性 (PCR RFLP)的方法对湖北汉族 12 0例哮喘患者及 112例无血缘关系的汉族健康人进行了STAT 6基因G2 96 4A位点多态性分析 ,用化学发光法测定血浆总IgE水平。结果　 (1)湖北汉族哮喘人群血浆总IgE(IU/ml)的对数值为 2 .2 6± 0 .74 ,非哮喘对照组为 1.19± 0 .85 ,有极显著性差异 (P <0 .0 1)。 (2 )湖北地区汉族人群基因型以GA型最为常见 ,其次为AA型和GG型 ,其等位基因以A型最为常见 ,其次为G型。与英国、荷兰等国人群该位点多态性相比 ,存在极显著性差异 (P <0 .0 1) ,而与日本人群接近 (P >0 .0 5 )。 (3)哮喘组与对照组STAT 6基因 3′非翻译区G2 96 4A位点的等位基因频率和基因型频率GG、GA、AA之间无显著性差异 (P >0 .0 5 ) ,并且哮喘组各基因型之间均与血浆IgE升高无关 (P >0 .0 5 )。结论　STAT 6基因 3′非翻译区G2 96 4A位点多态性与湖北汉族人哮喘易感性和血浆总IgE水平无明显相关性     

血清淀粉样蛋白A1基因多态性与冠心病的相关性

目的研究血清淀粉样蛋白A1(SAA1)基因多态性及与冠心病的关系。方法采用聚合酶链反应-限制性片段长度多态性分析(PCR-RFLP)等,分析183例冠心病患者和152例健康人对照组的SAA1基因多态性。结果2组均检出了SAA1的3种等位基因和6种基因型,分别为1.1、1.3、1.5和1.1/1.1、1.1/1.5、1.1/1.3、1.3/1.3、1.3/1.5、1.5/1.5。对照组等位基因1.5频率显著高于冠心病组(P<0.005);冠心病组1.1/1.1基因型频率显著高于对照组(P<0.05),而1.5/1.5型显著低于对照组(P<0.05)。冠心病组内不同基因型间TG和LDL-C的水平有显著性差异。1.1/1.1型的TG和LDL-C水平较高,HDL-C值最低;而1.5/1.5型的TG最低,HDL-C值却最高。结论SAA1的等位基因1.1可能与TG和LDL-C水平的升高有一定的关系,可促使冠心病的发生;而等位基因1.5则可能对心血管有一定的保护作用。     

Associations between single-nucleotide polymorphisms of the adiponectin gene,serum adiponectin levels and increased risk of type 2 diabetes mellitus in Iranian obese individuals

Abstract

Introduction: Adiponectin is an adipose tissue-secreted hormone with important metabolic effects. There have been inconsistent reports about SNPs of the adiponectin gene and risk of type 2 diabetes (T2DM). The aim of this study was to investigate any association between SNPs (+45 T/G and +276 G/T) of the adiponectin gene with serum adiponectin levels, metabolic factors and risk of T2DM in obese individuals. Design and methods: Genotyping for two common SNPs of adiponectin gene was performed in 50 unrelated obese type 2 diabetic patients and 52 obese non-diabetic control subjects by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Lipid profile was measured by enzymatic methods. Serum adiponectin, insulin, leptin and glucose levels were measured by immunoassay, and glucose oxidase methods, respectively. Results and conclusion: It was observed that obesity and T2DM are associated with low serum adiponectin levels. The G allele and TG/GG genotype of SNP 45 occurred more frequently than the T allele and TT genotype in T2DM patients compare to the controls (p<0.05). Subjects with the G/G + TG genotype of SNP 45 were at increased risk for T2DM [Odds Ratio (OR) 2.574; 95% Confidence Interval (CI) 1.051–6.302; p=0.036] compared with those T/T genotype. There was no statistically significant difference in allele and genotype frequencies of SNP 276 comparing control group with T2DM group. Thus, our results demonstrated that, adiponectin SNP 45T/G, rather than SNP 276G/T, is more associated with risk of T2DM in obese individuals.     

哮喘控制测试量表与一秒率的相关性研究

目的:探讨哮喘控制测试(ACT)量表与FEV1%的相关关系.方法:84例确诊为支气管哮喘患者填写ACT量表和进行肺功能测试,其中59例经规范治疗(75±15)d后依嘱复诊并再次填写ACT量表和行肺功能测试,对前后2次所得数据以FEV1%结果排序,以FEV1%基础值按≤79%(组1)和≥80%(组2)分为2组进行t检验和相关分析.结果:规范治疗前后,组1 FEV1、FEV1%、PEF、PEF%和ACT均显著低于组2(P<0.01),且ACT得分与FEV1%和PEF%结果高度一致;FEV1%均与FEV1、PEF、PEF%和ACT呈明显的正相关关系(P<0.01).结论:ACT与评价支气管哮喘症状控制好坏的客观指标FEV1%和PEF%具有明显的相关性和一致性,尤其是ACT简单明了,问题高度浓缩且准确精炼,特别对缺乏肺功能检测设备的基层乡镇卫生院不失为一个简单易行且可信度高的评价工具.     

载脂蛋白B基因XbaⅠ、EcoRⅠ位点多态性与胆石病关系的研究

目的:研究载脂蛋白B基因XbaⅠ、EcoRⅠ位点多态性和胆石病之间的关系.方法:通过病例对照研究设计,采用PCR-RFLP技术对106例胆石病患者和105例对照者进行基因分析.结果:胆石病组和对照组ApoB基因XbaⅠ位点X+X-、X-X-基因型构成显著不等;胆石病组X+等位基因频率显著高于对照组(0.104 vs 0.052);胆石病组和对照组ApoB基因EcoR Ⅰ位点E+E-和E+E+基因型频率构成差异显著,病例组E-等位基因频率显著高于对照组.结论:胆石病发生与ApoB基因XbaⅠ、EcoRⅠ位点多态性存在关联,XbaⅠX+等位基因和EcoRⅠ E-等位基因可能为胆石病的易感基因.     

视神经脊髓炎患者HLA-DPB1等位基因多态性的研究

目的探讨视神经脊髓炎（neuromyelitis optica，NM0）患者人类白细胞抗原（HLA）-DPBl等位基因的多态性。方法采用基于测序的分型方法（sequence-based typing，SBT）分析13例NMO患者的HLA-DPBl等位基因的多态性。结果13例NMO患者中共检测到6种HLA-DPBl等位基因片段。HLA-DPBl^＊0501的频率显著高于HLA-DPBl^＊0201、HLA-DPBl^＊0202、HLA-DPBl^＊0301、HLA-DPBl^＊1301、HLA-DPBl^＊2101（P〈0．05）。结论在NMO患者的HLA-DPBl等位基因多态性的研究中，HLA-DPBl^＊0501的频率显著高于其他，推测HLA-DPBl^＊0501可能与NMO的易患性有关。     

Remote FEV1 Monitoring in Asthma Patients: A Pilot Study

Forced expiratory volume in one second (FEV₁) is a critical parameter for the assessment of lung function for both clinical care and research in patients with asthma. While asthma is defined by variable airflow obstruction, FEV₁ is typically assessed during clinic visits. Mobile spirometry (mSpirometry) allows more frequent measurements of FEV₁, resulting in a more continuous assessment of lung function over time and its variability. Twelve patients with moderate asthma were recruited in a single‐center study and were instructed to perform pulmonary function tests at home twice daily for 28 days and weekly in the clinic. Daily and mean subject compliances were summarized. The agreement between clinic and mobile FEV₁ was assessed using correlation and Bland‐Altman analyses. The test‐retest reliability for clinic and mSpirometry was assessed by interclass correlation coefficient (ICC). Simulation was conducted to explore if mSpirometry could improve statistical power over clinic counterparts. The mean subject compliance with mSpirometry was 70% for twice‐daily and 85% for at least once‐daily. The mSpirometry FEV₁ were highly correlated and agreed with clinic ones from the same morning (r = 0.993) and the same afternoon (r = 0.988) with smaller mean difference for the afternoon (0.0019 L) than morning (0.0126 L) measurements. The test‐retest reliability of mobile (ICC = 0.932) and clinic (ICC = 0.942) spirometry were comparable. Our simulation analysis indicated greater power using dense mSpirometry than sparse clinic measurements. Overall, we have demonstrated good compliance for repeated at‐home mSpirometry, high agreement and comparable test‐retest reliability with clinic counterparts, greater statistical power, suggesting a potential for use in asthma clinical research.

Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

☑ Forced expiratory volume in one second (FEV1) is the gold standard in clinical care and research practice for assessing patients with asthma. Mobile spirometry (mSpirometry) provides an opportunity to collect frequent repeated measures remotely with minimum disruption to everyday life.

• WHAT QUESTION DID THIS STUDY ADDRESS?

☑ We sought to estimate concordance of mobile and clinic measures, establish patient compliance, assess diurnal variation of FEV₁, and explore whether at‐home repeated FEV1 measures would improve statistical power over traditional clinic measures.

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

☑ The mSpirometry FEV1 measurements were strongly correlated with clinic FEV1 from both the same morning (r = 0.993) and same afternoon/evening (r = 0.988). The mean subject compliance with mSpirometry was 85.3%. Our simulation analysis indicated a higher power using dense mSpirometry measurements.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

☑ Deploying mSpirometry in clinical trials is likely to improve statistical power.

Asthma is characterized by airway inflammation, airway hyper‐responsiveness, and variable airflow obstruction. ¹ Despite advances in our understanding of its pathophysiology, biomarker identification, and phenotyping, many patients remain poorly controlled. Asthma displays a strong circadian rhythm, which can cause symptom variability throughout a 24‐hour period. ² , ³ Clinical trials of novel drugs in asthma are faced with the challenge of measuring changes in lung function in this condition, which displays variable airflow obstruction, including diurnal fluctuations.Forced expiratory volume in 1 second (FEV₁) is the gold standard for monitoring lung function in clinical care and research. ⁴ Traditionally, measurements of lung function are performed during clinic visits. However, the frequency of measurements is often limited in clinical trials due to feasibility considerations for patients and cost. Asthma is characterized by airflow obstruction, which displays a diurnal pattern. Diurnal variation is observed in lung function in healthy individuals ⁵ and is greater in patients with asthma. ⁶ The lowest FEV₁ measurements are observed in early morning hours coinciding with increased symptoms and airway inflammation. ⁷ The requirement for clinic visits limits the ability to capture this variability. These limitations impose requirements of a relatively large sample size for drug development clinical trials to control for measurement variability. Furthermore, frequent clinic visits can limit patient participation.It is well known that multiple measures improve the accuracy of a measurement and therefore provide greater statistical power to detect a treatment difference in a measure with fewer patients. ⁸ The ability to monitor FEV₁ frequently may therefore be of benefit in clinical trials that evaluate treatment interventions in asthma. Frequent FEV₁ assessments can also help to account for diurnal variation. FEV₁ monitoring using mobile spirometers (mSpirometers) provides an opportunity to do at‐home monitoring, collect dense data, and minimize the effect of random anomalous tests results that may occur during sparse clinic visits. Although mSpirometers provide convenient means for collecting lung function data at home, a concern about this modality is related to patient compliance and willingness to put the best effort to perform expiratory maneuvers while unsupervised.The recent advances in remote FEV₁ monitoring demonstrated high correlation and small mean differences between at‐home mobile handheld and clinic‐based FEV₁ measurements in the context of randomized clinical trials in asthma ⁹ and chronic obstructive pulmonary disease (COPD). ¹⁰ However, the studies describing a comparison of clinic and mSpirometry data are limited, and study findings may be device‐specific. Moreover, patient compliance with mSpirometry was reported only in patients with COPD, ¹⁰ indicating a need to establish compliance data in different populations, including asthma. Additionally, to our knowledge, no study has investigated if FEV₁ repeated measurements at home can improve statistical power to detect a treatment effect. The aim of our study was to build on previous findings, by verifying agreement between clinic and mobile FEV₁ measurements using a different spirometer device, establishing patient compliance in patients with moderate asthma. Furthermore, we used the data to perform power simulation to estimate the effect sizes that can be detected from either weekly clinic measurements or daily measurements at home in clinical trials.     

综合心理干预治疗儿童哮喘的临床疗效分析

目的　探讨放松训练、家庭治疗、认知和行为治疗综合心理干预对哮喘患儿的临床治疗效果。方法　采用双盲 ,随机对照方法 ,对诊断为儿童哮喘符合纳入标准的 116例患儿分为治疗组 6 0例 ,对照组 5 6例 ,给予同样药物治疗 ,治疗组同时进行综合心理干预治疗前后观察两组临床疗效 ,日夜间记分及呼吸峰流速 (PEF)等。结果　治疗组在临床疗效、日间记分、PEF等方面均优于对照组 (P<0 .0 5 ,0 .0 1)。结论　综合心理干预治疗儿童哮喘疗效确切     

529例中国汉族健康人群HLA-DQB1基因型遗传特征研究

目的 探讨中国汉族健康人群HLA-DQB1基因型遗传特征.方法 应用聚合酶链反应-测序分型(polymerase chain reaction sequence-based typing,PCR-SBT)法对529例中国汉族健康人群HLA-DQB1位点进行基因测序分型.结果 在529例中国汉族健康人群中,共检出18种等...     

小儿支气管哮喘与肺炎支原体感染关系的临床研究

目的探讨小儿支气管哮喘与肺炎支原体(MP)感染的关系。方法儿童哮喘专科门诊及住院哮喘发作期患儿193例(哮喘组)及同期就诊的呼吸道感染患儿213例(对照组),采用MP被动冷凝集法检测血清肺炎支原体抗体(MP-Ab)。结果哮喘组MP-Ab阳性93例,阳性率48.2%;对照组阳性53例,阳性率25.8%,两组比较差异显著(P<0.01)。结论MP感染与儿童哮喘关系密切,MP导致呼吸道慢性炎症,进而改变呼吸道高反应性是最根本的机制。对哮喘发作期的患儿要考虑MP感染可能,应常规行MP-Ab检查。