新生儿支气管肺发育不良TLR-10、SP-A1基因多态性及其与病情程度的关系

目的 探讨新生儿支气管肺发育不良（BPD）患儿Toll样受体10(TLR-10)、肺泡表面活性物质蛋白A1(SP-A1)基因多态性及其与病情程度的关系。方法 选取承德市中心医院83例BPD患儿作为观察组,另选取83例同期健康新生儿作为对照组。比较两组血清TLR-10、SP-A1水平、TLR-10rs11096955位点、SP-A1AA50位点基因多态性,分析两者基因多态性对BPD易感性的影响及与病情程度的关系。结果 观察组血清TLR-10、SP-A1水平高于对照组（P<0.05）;TLR-10 rs11096955位点、SP-A1 AA50位点基因型分布具有人群代表性。观察组与对照组TLR-10 rs11096955位点、SP-A1 AA50位点基因型、等位基因频率差异有统计学意义（P<0.05）;TLR-10 rs11096955位点AA基因型BPD易感性是AC/CC的1.401倍;SP-A1 AA50位点GG基因型BPD易感性是GC/CC的1.692倍;TLR-10 rs11096955位点AA基因型、等位基因A频率、SP-A1 AA50位点GG基因型、等位基因G频率与...     

肺表面活性物质蛋白B基因多态性与新生儿呼吸窘迫综合征易感性的研究

目的探讨肺泡表面活性物质蛋白B（SPB）基因多态性与新生儿呼吸窘迫综合征易感性的关系。方法收集华中科技大学同济医学院附属同济医院的新生儿呼吸窘迫综合征（NRDS）诊断病例为病例组,并按1∶2比例收集胎龄和出生体重相匹配的无明显感染症状早产儿为对照组。应用聚合酶链反应-限制性片段长度多态（PCR-RFLP）分析技术及基因测序技术检测SPB-18A/C及SPB1580C/T多态性,观察两组间基因型频率和等位基因频率的差异。并复习文献比较本研究汉族与其他种族人群等位基因频率的差异。结果 2008至2010年NRDS组91例,对照组182名进入分析。①SPB-18A/C基因在NRDS组AA,AC,CC基因型频率分别为11.0%、40.7%和48.4%,对照组分别为6.6%、31.3%和62.1%;两组基因型频率差异无统计学意义（P〉0.05）;NRDS组A等位基因频率显著高于对照组（31.3%vs22.3%）。②SPB1580C/T基因在NRDS组TT、TC和CC基因型频率分别为5.5%、63.7%和45.1%,对照组分别为30.8%、6.6%和48.4%;两组基因型频率差异无统计学意义（P〉0.05）;NRDS组C等位基因频率显著高于对照组（79.1%vs70.9%）。③本研究汉族人、美国人、巴西人和丹麦人SPB1580等位基因C频率分别为79%、35%、41%和46%,差异有统计学意义（P〈0.05）,与日本人群等位基因C频率（72%）差异无统计学意义（P〉0.05）;本研究汉族人、巴西人、美国人和丹麦人SPB-18等位基因A频率分别为31%、58%、57%和61%,差异有统计学意义（P〈0.05）。结论本研究汉族人群SPB-18A/C及SPB1580C/T基因多态性是NRDS的危险因素。不同种族人群SPB1580C/T和SPB-18A/C基因多态性分布存在明显差异。     

维生素D早期干预对新生大鼠支气管肺发育不良的影响

目的 探究维生素D (VitD)的早期干预对新生大鼠支气管肺发育不良(BPD)的保护效果.方法 95％高氧暴露建立新生大鼠BPD模型,分为正常组、高氧组、高氧+低剂量VitD组和高氧+高剂量VitD组.大鼠生后7d连续腹腔注射VitD[1 ng/(g·d)和3 ng/(g·d)],观察第3、5、9日大鼠生存率和体重,苏...     

肺表面活性物质相关蛋白A基因多态性与新疆蒙古族慢性阻塞性 肺疾病患者的发病

背景：目前慢性阻塞性肺疾病的遗传易感性机制未完全阐明。肺表面活性物质相关蛋白A可能在其易感性机制中发挥重要作用,且可能有种族差异。 目的：探讨肺表面活性物质相关蛋白A基因位点aa62、aa219多态性与新疆蒙古族慢性阻塞性肺疾病易感性的关系。 方法：采用病例-对照研究设计,纳入新疆蒙古族吸烟慢性阻塞性肺疾病患者119例(病例组)和吸烟健康体检者116例(对照组)为研究对象。采用Taqman探针标记荧光定量PCR法检测肺表面活性物质相关蛋白A基因的aa62(CCA/CCG,rs1136451)和aa219(CGG/TGG,rs4253527)位点的单核苷酸多态性,获得各基因型和等位基因的分布情况。 结果与结论：在aa62位点,两组的基因型频率(AA,AG、GG)及等位基因频率(A、G)比较差异均有显著性意义 (χ²=7.164,P=0.028;χ²=2.239,P=0.019);且基因型频率在肺功能Ⅱ级与Ⅲ级慢性阻塞性肺疾病患者间差异有显著性意义(χ²=8.721,P=0.013)。在aa219位点,两组基因型频率(CC,CT)及等位基因频率(C、T)比较差异均无显著性意义(χ²=0.367,P=0.545;χ²=0.332,P=0.565)。提示肺表面活性物质相关蛋白A基因aa62位点多态性可能与新疆蒙古族吸烟慢性阻塞性肺疾病的易感性相关。     

肺泡表面活性物质相关蛋白A基因多态性与慢性阻塞性肺疾病易感性的关系

目的探讨中国汉族人肺泡表面活性物质相关蛋白A(surfactantproteinA,SPA)基因多态性与慢性阻塞性肺疾病(chronicobstructivepulmonarydisease,COPD)易感性的关系。方法应用聚合酶链反应及限制性片段长度多态性,检测SPA基因型在88例吸烟COPD患者和87名健康吸烟者中频率的分布。结果88例COPD患者+186位点AA、AG、GG3种基因型的分布频率分别为86.4%、12.5%和1.1%,而对照组为66.7%、27.6%和5.7%,两组比较差异有统计学意义(P<0.05)。+655位点CC、CT、TT3种基因型的分布频率分别为65.9%、27.3%和6.8%,而对照组为52.9%、36.8%和10.3%,两组比较差异无统计学意义(P>0.05)。+667位点AA、AC、CC3种基因型的分布频率分别为47.2%、43.2%和9.1%;而对照组这三个基因基因型的分布频率分别为35.6%、51.7%和12.6%,两组比较差异无统计学意义(P>0.05)。结论SPA+186位点基因多态性可能与中国汉族人吸烟COPD患者的发病有关,但该位点的突变怎样影响SPA的表达和活性,还有待进一步的研究。     

肺表面活性蛋白A基因多态性与呼吸道合胞病毒下呼吸道感染的相关性研究

目的探讨肺表面活性蛋白（SP）-A1-1101C/T和SP-A2-1649G/C位点基因多态性与呼吸道合胞病毒下呼吸道感染（RSV-LRTI）的相关性。方法应用聚合酶链反应-限制性酶切片段长度多态性（PCR-RFLP）分析法检测200例病例组和150例健康对照组2个位点的基因多态性,并进行基因型、等位基因型频率分析;采用DNA测序法进行测序分析。结果 1.病例组SP-A1-1101C/T位点TT、CT基因型频率分别为76.0%、24.0%,T、C等位基因频率分别为88.0%、12.0%;对照组TT、CT基因型频率分别为80.7%、19.3%,T、C等位基因频率分别为90.3%、9.7%,两组基因型及等位基因频率差异无统计学意义（χ2=1.088、0.953,P〉0.05）。2.病例组SP-A2-1649G/C位点CC、CG、GG基因型频率分别为41.5%、50.5%、8.0%,C、G等位基因频率分别为66.8%、33.2%;对照组CC、CG、GG基因型频率分别为43.3%、49.3%、7.4%,C、G等位基因频率分别为68.0%、32.0%,两组基因型及等位基因频率无统计学意义（χ2=0.141、0.122,P〉0.05）;但该位点基因型和等位基因在轻度和重度患儿间的差异有统计学意义（χ2=6.664、5.207,P〈0.05）,携带G等位基因的个体患重度RSV-LRTI的风险是患轻度风险的1.656倍,（OR=1.656,95%CI：1.072～2.559,P=0.023〈0.05）。结论温州地区汉族儿童存在SP-A1-1101C/T、SP-A2-1649G/C基因多态性,未发现其与RSV-LRTI疾病易感性存在关联,但携带SP-A2-1649G等位基因的个体患重度RSV-LRTI的风险是患轻度风险的1.656倍,表明G等位基因可能是影响RSV-LRTI疾病严重程度的一个候选基因。     

肺泡外肺表面活性物质结合蛋白A研究进展

肺表面活性物质结合蛋白A(SP A)是肺表面活性物质中最主要的蛋白成分 ,主要由Ⅱ型肺泡上皮细胞及clara细胞分泌。研究发现 ,在肺泡外也存在相对低水平的SP A ,在传导气道、中耳、咽鼓管、鼻旁窦、胃肠道、生殖道、胸腺、脾脏、间皮及滑膜细胞内均可检测到SP AmRNA及蛋白 ,SP A可与病原及巨噬细胞结合 ,增强巨噬细胞吞噬杀灭病原 ,这些部位的SP A可能与宿主防御有关 ,在某些部位也有降低表面张力的作用     

肺表面活性物质相关蛋白A的免疫调节功能

肺表面活性物质相关蛋白A(SP A)是肺表面活性物质相关蛋白中最重要的成分之一。作者概述了SP A的分子结构与免疫的关系 ,以及对微生物、炎症细胞、炎症介质和抗体等的作用 ,提示SP A具有广泛的免疫调节功能。最后提出一些值得研究的问题     

肺表面活性物质结合蛋白A研究进展

SP A是肺表面活性物质的重要蛋白成分 ,在维持PS内环境稳定和机体免疫方面发挥重要作用。最近研究表明 ,肺表面活性物质磷脂和SP A也存在于肺泡外肺组织及身体其它器官。就SP A受体、SP A基因表达调控、不同疾病时SP A水平变化及其在肺泡外组织中的分布与功能方面的相关研究进展作一简要综述。     

Surfactant protein B gene polymorphisms is associated with risk of bronchopulmonary dysplasia in Chinese Han population

Objective: To investigate the relationship between Surfactant protein B (SP-B) gene polymorphisms and bronchopulmonary dysplasia (BPD) development in preterm infants of China Han ethnic population. Methods: SP-B gene polymorphisms were studied in 134 neonates who were born at < 32 weeks of gestation, with the diagnosis of BPD and in a control group of 168 preterm infants without BPD. Genotyping for SP-B was performed by polymerase chain reaction (PCR) and gene sequencing. Results: In this study, three of the SNP genotypes, -18C/A, 1580C/T and 4564T/C were common identified in SP-B gene. The -18C/A genotype was found to be significantly associated with BPD (χ² = 10.741, P < 0.01), with P < 0.01 for the dominant model (OR = 1.712, 95% CI = 1.228-2.3894) and the allelic model (OR = 1.787, 95% CI = 1.276-2.502). The 1580C/T genotype was found to be associated with BPD (χ² = 7.014, P < 0.05), with P < 0.05 for the dominant model (OR = 0.752, 95% CI = 0.593-0.954) and P < 0.01 for the allelic model (OR = 0.706, 95% CI = 0.548-0.909). The 4564T/C genotypes and alleles were found not to be associated with BPD (χ² = 3.399 and 3.227, P > 0.05). Conclusion: SP-B -18C/A and 1580C/T polymorphisms are associated with BPD. The 1580C/T polymorphism was protective while the -18C/A polymorphism increased the risk for BPD. SP-B 4564T/C polymorphism is not associated with BPD.     

Involvement of surfactant protein D in emphysema revealed by genetic association study

Surfactant protein D (SFTPD) induces emphysema in knockout mice, but the association of SFTPD with chronic obstructive pulmonary disease (COPD) and emphysema in humans is unclear. Therefore, we aimed to determine the association between genetic variations in SFTPD and susceptibility to COPD and emphysema.Two populations were studied: population A comprised 270 smokers, including 188 COPD and 82 at-risk subjects, and population B comprised 1131 autopsy cases including 160 cases with emphysema. Six single-nucleotide polymorphisms (SNPs) that tagged the linkage disequilibrium blocks on the entire SFTPD gene were genotyped; the associations of the genotypes with COPD, pulmonary function, percentage of the low-attenuation area (LAA%), and percentage of the airway wall area (WA%) were determined in population A. In population B, the associations of the genotypes with emphysema were assessed.A C allele at SNP rs721917 that results in the replacement of Met with Thr at position 11 in SFTPD was positively correlated with the LAA% in the upper lung (P = 1.1 × 10(-5)) and overall LAA% (P = 1.0 × 10(-4)), and negatively correlated with the serum concentration of SFTPD (P = 7 × 10(-11)) in the population A. The C/C (rs721917/rs10887199) haplotype was associated with emphysema in both the populations.Subjects with a C allele at rs721917 have a lower serum SFTPD concentration and are more susceptible to emphysema. This suggests a protective effect of SFTPD against COPD and emphysema.     

维生素D代谢相关基因多态性研究进展

维生素D缺乏是佝偻病的主要病因,遗传因素在其发生发展中的作用正逐渐受到重视.与维生素D代谢相关的基因包括:维生素D受体基因(vitamin D receptor,VDR)、维生素D结合蛋白基因(vitamin D-binding protein,DBP)、细胞色素P450基因(cytchrome P450,CYP)、NADSYN1/DHCR7基因.该文就这些基因多态性与维生素D代谢关系的进展作一阐述.

Abstract：

The major cause of tickets is Vitamin D deficiency.Genetic factors contributing to the pathogenesis of rickets have been investigated with more and more attention.Genes related to vitamin D metabolism include:VDR gene,DBP gene,CYP gene and NADSYN1/DHCR7 gene.In this article,we review the current status and progress in gene polymorphisms and their association with vitamin D metabolism.     

Association between single nucleotide polymorphisms of surfactant protein D and allergic rhinitis in Chinese patients

The development of allergic rhinitis is considered to be determined by the interaction between genetic and environmental factors. Surfactant protein D (SP-D) has been proposed to offer protection against allergenic challenge at various levels in allergic responses. The present study aimed to investigate whether polymorphisms within the SFTPD gene (Met11Thr, Ala160Thr, and Ser270Thr) are associated with allergic rhinitis. Genotyping of SFTPD polymorphisms was performed using the pyrosequencing method. The study population comprised 216 patients with allergic rhinitis and 84 normal controls. The frequency of 11Thr/Thr genotype and Thr allele in the patient group was significantly higher than that in the control group after applying Bonferroni corrections ( P  = 0.007 and P  = 0.006, respectively). Our subjects with the 11Thr/Thr genotype are more susceptible to allergic rhinitis. There were no significant differences between the patient group and the control group for frequencies of genotypes and alleles in either Ala160Thr or Ser270Thr single nucleotide polymorphisms ( P  > 0.05). No significant associations could be detected between any of these three SFTPD gene polymorphisms and the skin prick test response ( P  > 0.05). Meanwhile, there was a lack of association between the three loci and the levels of serum total immunoglobulin E ( P  > 0.05). In summary, our results suggest that the Met11Thr polymorphism in SP-D plays a major role in the genetic predisposition to allergic rhinitis in Chinese adult population, whereas the other two SP-D polymorphisms displayed no significant association with allergic rhinitis.     

我国福建汉族人HSP70基因多态性分析

目的了解福建省汉族人HSP70基因多态性分布，进而为探讨HSP70基因多态性与疾病的相关性提供遗传背景资料。方法应用聚合酶链反应技术、限制性内切酶分析检测了127名福建汉族正常人的HSP70基因3个多态性位点，并比较了部分不同地区和人群之间的基因型与等位基因频率。结果福建汉族人HSP70-1基因型（GG，GC和CC）分布频率分别是55．1％、40．2％和4．7％；HSP70-2基因型（从，AG和GG）分布频率分别是44．1％、铝．8％和6．9％；HSP70-hom基因型（Tr，TC和CC）分布频率分别是59.8％、37．0％和3．2％；HSP70-1等位基因频率G和C分别是75．2％和24．8％；HSP70-2等位基因频率A和G分别是68．5％和31．5％；HSP70-hom等位基因频率T和C分别是78．3％和21．7％。福建汉族人HSP70-1的基因型分布和等位基因频率同日本、墨西哥人群比较差异无统计学意义，与美国和西班牙人比较，差异有统计学意义（P〈0．01）。福建汉族人HSP70-1的GG纯合型（55．1％）显著高于美国（42．6％）和西班牙（33．0％）人群；福建汉族人HSP70-2的基因型分布和等位基因频率与日本人比较差异无统计学意义，与墨西哥、美国和西班牙人群比较，差异有统计学意义（P〈0．05），福建汉族人HSP70-2的AA纯合型（44．1％）高于墨西哥（23．O％）、美国（38．8％）和西班牙（20．O％）人群；福建汉族人群的HSP70-hom基因型和等位基因频率分布同日本、墨西哥、美国和西班牙人群的基本一致，差异无统计学意义，福建汉族人群的HSP70基因型和等位基因频率分布同中国台湾汉族人基本一致，差异无统计学意义，与武汉地区汉族人某些位点存在差异。结论福建汉族人HSP70基因多态性分布不同于某些地区的人群，具有种族和地区差异。     

Cord blood levels of IL-6, IL-8 and IL-10 may be early predictors of bronchopulmonary dysplasia in preterm newborns small for gestational age

Introduction: Various cytokines have been associated to the occurrence of bronchopulmonary dysplasia (BPD) in preterm neonates. AIM: To establish an association between cord blood cytokines and BPD, so that they could be used, in clinical practice, as early markers of BPD. Material and methods: Preterms less than 30 weeks gestational age, were analysed by ELISA microassay for venous cord blood IL-1β, IL-6, IL-8, TNF-α and IL-10, and compared between the BPD and non-BPD groups. Results: One hundred and fifty neonates completed the study; 31 (21%) small for gestational age (SGA); 16 were deceased before 28 days of life; 36 developed mild BPD and 20 developed moderate/severe BPD. Elevated cord blood IL-8 was associated with death or moderate/severe BPD. SGA patients with moderate/severe BPD presented higher cord blood values of IL-8, lower IL-6 and IL-10 when compared with SGA without moderate/severe BPD; and higher IL-8 levels when compared with patients without moderate/severe BPD. Conclusion: These results support an association between cord blood IL-8 and moderate/severe BPD, independently of the intra-uterine growth; and the association of cord blood IL-6 and IL-10 and moderate/severe BPD in SGA preterm newborns.     

The contribution of postnatal steroid administration to early brain damage in preterm babies with bronchopulmonary dysplasia

Background/aimPostnatal corticosteroids are commonly used to treat bronchopulmonary dysplasia (BPD). We aimed to show whether S100 calcium-binding B (S100B), neuron-specific enolase (NSE), Tau protein or microtubule-associated protein tau (MAPT), and glial fibrillary acid protein (GFAP) levels would provide any evidence of early neurological damage in premature infants receiving postnatal low dose dexamethasone therapy for BPD treatment.Materials and methods In this cohort study, 136 preterm infants diagnosed with BPD at ≤32 weeks of gestation formed the study group, and 64 preterm infants formed the control group. NSE, S100B, GFAP, and MAPT levels were first measured before the postnatal corticosteroid treatment in both the patient and the control group on the 28th day and, for a second time, after treatment termination in the patient group.Results There were significant differences between the measured GFAP, MAPT, and NSE values of the BPD and control groups on the 28th day, whereas there was no significant difference between the measured S100B values of the two groups. There were a statistically significant difference between the NSE values measured on the 28th day and after the treatment within the BPD group, whereas no significant difference existed between the GFAP, MAPT, and S100B values.Conclusion NSE levels, which indicate brain damage in the early period, increased in preterm babies with BPD who had been administered postnatal dexamethasone.     

我国汉族儿童维生素D受体基因多态性分布

目的　了解我国汉族儿童维生素D受体 (VDR)基因多态性分布。方法　利用限制性内切酶BsmⅠ ,采用聚合酶链反应限制性片段长度多态性技术 (PCR -RFLP) ,对 1 69名健康汉族儿童进行了VDR基因分型 ,并计算其基因型频率分布。结果　中国汉族儿童VDR基因bb、Bb、BB基因型分别为 91 1 2 %、7 1 %、1 77%,明显不同于高加索人种 ,与韩国人较为相似。结论　VDR基因多态性具有种族差异性     

Surfactant protein A and surfactant protein D variation in pulmonary disease

Surfactant proteins A (SP-A) and D (SP-D) have been implicated in pulmonary innate immunity. The proteins are host defense lectins, belonging to the collectin family which also includes mannan-binding lectin (MBL). SP-A and SP-D are pattern-recognition molecules with the lectin domains binding preferentially to sugars on a broad spectrum of pathogen surfaces and thereby facilitating immune functions including viral neutralization, clearance of bacteria, fungi and apoptotic and necrotic cells, modulation of allergic reactions, and resolution of inflammation. SP-A and SP-D can interact with receptor molecules present on immune cells leading to enhanced microbial clearance and modulation of inflammation. SP-A and SP-D also modulate the functions of cells of the adaptive immune system including dendritic cells and T cells. Studies on SP-A and SP-D polymorphisms and protein levels in bronchoalveolar lavage and blood have indicated associations with a multitude of pulmonary inflammatory diseases. In addition, accumulating evidence in mouse models of infection and inflammation indicates that recombinant forms of the surfactant proteins are biologically active in vivo and may have therapeutic potential in controlling pulmonary inflammatory disease. The presence of the surfactant collectins, especially SP-D, in non-pulmonary tissues, such as the gastrointestinal tract and genital organs, suggest additional actions located to other mucosal surfaces. The aim of this review is to summarize studies on genetic polymorphisms, structural variants, and serum levels of human SP-A and SP-D and their associations with human pulmonary disease.