MBL基因多态性及血清MBL浓度与狼疮性肾炎的关系

目的探讨狼疮性肾炎(LN)与甘露聚糖结合凝集素(MBL)基因第一外显子54位密码子和启动子序列多态性及血清MBL浓度的关系。方法用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析技术和序列特异性引物PCR(SSP-PCR)技术分析对照组(n=40)和LN组(n=49)MBL第一外显子54位密码子及启动子区-550的H/L和-221的X/Y多态性。用ELISA法测定血清MBL浓度。结果LN组MBL第54位密码子GAC等位基因频率高于对照组(0.173vs0.112),但无显著性差异;启动子单倍型LX显著高于对照组(P(0.05);对照组GGC/GGC基因型和启动子HY/HY型的血清MBL浓度显著高于LN组(P<0.05～0.01)。LN组和对照组中血清MBL浓度低于1000μg/L者分别为40.8%和17.5%,两组相比有显著性差异(P(0.05)。结论LN患者血清MBL浓度显著降低与MBL基因启动子LX型增加有关。     

系统性红斑狼疮病人甘露糖结合蛋白基因多态性

目的　探讨 SL E病人 MBP基因多态性。方法　用多聚酶链反应 -限制性片段长度多态性 ( PCR-RFLP)法检测 5 6名正常健康者和 62名 SL E病人外显子 1的第 5 4号密码子多态性 ( GGC/GAC)。结果　正常人 MBP基因型分布频率 GGC/GGC为 76.8% ( 4 3/5 6) ,GGC/GAC为 2 3.2 % ( 1 3/5 6) ;SLE病人GGC/GGC为 69.4% ( 4 3/62 ) ,GGC/GAC为 2 9.0 % ( 1 8/62 ) ,GAC/GAC为 1 .61 % ( 1 /62 ) ;与正常人相比 ,无显著性差异。红斑狼疮病人各组之间等位基因分布频率亦无统计学差异 ( P>0 .0 5 )。结论　患 SL E疾病危险性与 MBP第 5 4号密码子基因变异无相关性     

反复呼吸道感染儿童血浆MBL水平及基因突变特征

目的探讨血浆甘露聚糖结合凝集素（MBL）水平及基因多态性与儿童反复呼吸道感染（RRTI）的关系。方法选择110例RRTI儿童及111例健康儿童（均为汉族）为研究对象。应用酶联免疫吸附试验（ELISA）方法检测其血浆MBL水平,聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法检测MBL基因第一外显子54密码子、57密码子基因型和多态性。结果 RRTI儿童血浆MBL水平显著低于健康儿童组（t=7.19,P〈0.01）;各年龄段RRTI儿童血浆MBL水平均明显低于同年龄段健康儿童组（t=2.15～3.55,P〈0.05、0.01）,但RRTI儿童各年龄段间比较差异无显著性（P〉0.05）。RRTI组MBL水平低下者检出率（23%）显著高于健康儿童组（6%）（χ2=9.12,P〈0.01）,MBL基因第一外显子54密码子基因型GGC/GGC、GGC/GAC、GAC/GAC分别对应高、中及低血清MBL水平。RRTI组MBL基因第一外显子54密码子等位基因GAC及GGC/GAC型突变杂合子频率显著高于健康儿童组（χ2=4.47～5.64,P〈0.05）。两组均未检出57密码子突变个体。结论 MBL缺陷是RRTI的重要原因,与低MBL水平相关的MBL基因第一外显子54密码子等位基因GAC是儿童RRTI的危险因素。     

慢性HBV感染者甘露糖结合蛋白基因多态性与HBV基因型的关系

目的探讨甘露糖结合蛋白(MBP)基因多态性及HBV基因型与慢性乙型肝炎(HBV)进展的关系。方法采用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)方法和实时荧光定量PCR(FQ-PCR)技术对360例慢性HBV感染者[其中66例无症状HBV携带者组(ASC组)、182例慢性乙型肝炎患者组(CH组)、112例肝硬化患者组(LC组)和65例对照组]的MBP基因第54号密码子多态性和HBV基因分型进行检测。结果 ASC组和轻、中型CH组均以B基因型占优势,MBP基因GGC/GAC基因型频率和GAC等位基因频率与对照组比较差异无统计学意义(P>0.05);重型CH组、代偿期LC组、失代偿期LC组均以C基因型占优势,MBP基因GGC/GAC基因型频率和GAC等位基因频率显著高于对照组(P<0.05),其中失代偿期LC组突变率最高(37.7%)。结论该地区乙型肝炎人群以B和C基因型为主;MBP基因第54号密码子突变与HBV感染的慢性化无明显关系,而与HBV C基因型及慢性HBV感染者的肝病进展有关。     

新疆哈萨克及维吾尔族SLE和RA患者MBL基因多态性调查

目的 对新疆哈萨克及维吾尔族人群中系统性红斑狼疮(SLE)及类风湿关节炎(RA)患者甘露糖结合凝集素基因54位密码子点突变进行测定并分析.方法 PCR-RFLP.结果 42例哈萨克族SLE患者基因频率:0.536(GGC),0.464(GAC);24例维吾尔族SLE患者基因频率:0.667(GGC),0.333(GAC);22例哈萨克族RA患者基因频率:0.614(GGC),0.386(GAC);15例维吾尔族RA患者基因频率:0.733(GGC),0.267(GAC).结论 MBL不同的基因型和这些疾病发生可能存在相关.     

甘露糖结合凝集素基因多态性与妊娠糖尿病的关系

摘要:目的：探讨甘露糖结合凝集素(MBL)基因外显子上的52、54、57密码子以及其启动子区域 550位点多态性与妊娠糖尿病(GDM)发病的关系。 方法：选取GDM患者、正常妊娠对照各75例,检测血糖、血压、血清MBL水平,并用基因测序法检测并分析MBL基因外显子上的52、54、57密码子以及启动子区域 550位点的序列特征。 结果：GDM组和正常妊娠对照组MBL基因外显子上的54位密码子和启动子区550位点存在多态性,并且其对应的等位基因频率存在统计学差异（χ²分别为5.811和6.475,P<0.05）,Logistic回归分析显示其突变型为GDM的危险因素。正常妊娠对照组血清MBL水平高于GDM组（t=3.10,P<0.05）。54位密码子位点的野生型、杂合型、纯合突变型血清MBL水平差异有统计学意义（F=81.939,P<0.05）。 结论: MBL基因外显子上的54密码子及启动子区 550位点多态性位点与南京地区汉族GDM有关。     

MBL ExonI54位点和NFκB1-94ins/del ATTG基因多态性与急性白血病患者化疗后粒细胞缺乏性发热的相关性研究

目的:探讨汉族人群的甘露聚糖结合凝集素(mannan-binding lectin,MBL)结构基因第1外显子第54位点和NFκB1基因启动序列-94ins/del ATTG基因多态性与初诊急性白血病患者首次化疗后发生粒细胞缺乏性发热的相关性。方法:检测汉族人群初诊急性白血病(M3型除外)接受首次化疗患者的MBL ExonI 54位点和NFκB1-94ins/del ATTG基因多态性分布,分析两种基因多态性与急性白血病患者首次化疗后发生粒细胞缺乏性发热的相关性。结果:共检测76例患者,并未发现MBL ExonI 54位点和NFκB1-94ins/del ATTG基因多态性与急性白血病患者化疗后粒细胞缺乏性发热相关,差异无明显统计学意义(P0.05);而且急性白血病患者化疗后粒细胞缺乏性发热组的MBL ExonI 54位点和NFκB1-94ins/del ATTG的不同基因型与患者的性别、年龄、不同疾病类型、首次化疗后疾病状态和化疗后的粒细胞缺乏性程度均无明显相关性(P0.05),但MBL ExonI 54位点突变(GGC54GAC)患者发生粒细胞缺乏性发热持续时间比无突变患者发生粒细胞缺乏性发热持续时间长(5 d vs 3 d P0.05)。结论:MBL ExonI 54位点和NFκB1-94ins/del ATTG基因多态性与汉族人群急性白血病患者首次化疗后发生的粒细胞缺乏性发热无关,但MBL ExonI 54位点突变(GGC54GAC)患者粒细胞缺乏性发热的持续时间更长。     

云南汉族人群Tim-1基因多态性与系统性红斑狼疮关联性研究

目的探讨Tim-1启动子区-416G〉C和-1454G〉A位点基因多态性与云南高原地区汉族人群系统性红斑狼疮（SLE）的遗传易感性有无关联。方法采用PCR-RFLP方法对132名云南汉族SLE病人和120名健康体检者Tim-1启动子区多态性位点-416G〉C和-1454G〉A的基因多态性进行检测,同时采用间接免疫荧光法检测其抗双链DNA抗体、抗Sm抗体、抗RNP抗体三种自身抗体。结果 SLE组和对照组Tim-1启动子区多态性位点-416G〉C的基因型及等位基因频率差异均无统计学意义（P〉0.05）,而-1454G〉A位点的基因型及等位基因频率在SLE组与对照组中的差异均有统计学意义（P〈0.05）;SLE组和对照组三种SLE相关自身抗体检测阳性率差异有统计学意义（P〈0.05）;SLE组两个位点不同基因型中三种自身抗体检测阳性率的差异均无统计学意义（P〉0.05）。结论云南汉族人群Tim-1启动子区-416G〉C和-1454G〉A位点存在单核苷酸多态性变异,且-1454G〉A位点多态性变异与SLE遗传易感性相关,但两位点不同基因型不会影响SLE相关自身抗体的表达。     

内皮型一氧化氮合酶基因多态性与高血压病发病相关性的研究

目的 研究内皮型一氧化氮合酶（eNOS）基因启动子-786位点及第七外显子第894位点多态性与高血压病发病的相关性.方法 采用病例对照研究的方法,以215名高血压病患者与108名健康中老年人的血白细胞为样本,应用聚合酶链反应一限制性片段长度多态性技术检测两组的内皮型一氧化氮合酶基因启动子-786位点T/C多态性及第七外显子第894位点G/T多态性,比较两组的基因型和等位基因的分布频率.通过两基因位点多态性的分布频率研究两基因变异在高血压病的发病中是否存在协同作用.结果 eNOS基因启动子-786位点T/T、T/C和C/C基因型在高血压病组中分别为22.79%、50.70%、26.51%,在正常中老年人组中分别为36.11%、52.78%、11.11%,此位点高血压病组与正常中老年人组的基因分布频率差异有显著性.eNOS基因第七外显子第894位点G/G、G/T和T/T基因型在高血压病组中分别为69.30%、22.33%、8.37%,在正常中老年人组中分别为82.41%、15.74%、1.85%,此位点高血压病组与正常中老年人组的基因分布频率差异有显著性.当如上两基因型为CC＋TT或TC＋TT时,经计算患高血压病的OR值明显大于基因型为TT＋GG者.结论 ①eNOS基因启动子-786位点及第七外显子第894位点基因多态性与高血压病的发病有一定程度的相关性;②eNOS基因启动子-786位点T/T及第七外显子894位点G/G是高血压病的保护性基因;③两基因变异在高血压病的发病中可能有一定程度的协同作用.     

甘露糖结合凝集素的基因多态性与复发性肾病综合征的关系

目的：探讨甘露糖结合凝集素（MBL ）的基因多态性与复发性肾病综合征的关系。方法对66例复发的肾病综合征患者和40例健康成人用序列特异性引物聚合酶链反应（SSP-PCR）和实时定量荧光聚合酶链反应分别检测MBL启动子和外显子1第54号密码子的基因多态性位点,同时采用酶联免疫吸附试验检测血清中MBL浓度。结果复发性肾病综合征患者和健康对照者中高表达MBL的基因型血清MBL浓度均高于低表达MBL的基因型,差异有统计学意义（P＜0．05）;复发的肾病综合征患者血清MBL浓度低于对照组,差异有统计学意义（P＜0．05）。复发性肾病综合征患者有前驱感染病史者,MBL的基因型低表达者多于高表达者,差异有统计学意义（P＜0．05）。结论推测MBL的基因变异导致血清MBL浓度降低,诱发感染发生,引起肾病综合征患者经常复发。     

Distinct alleles of mannose-binding lectin (MBL) and surfactant proteins A (SP-A) in patients with chronic cavitary pulmonary aspergillosis and allergic bronchopulmonary aspergillosis.

BACKGROUND: Distinct host immune status predisposes to different forms of pulmonary aspergillosis. METHODS: Patients with chronic cavitary pulmonary aspergillosis (CCPA; n=15) or allergic bronchopulmonary aspergillosis (ABPA; n=7) of Caucasian origin were screened for single nucleotide polymorphisms (SNPs) in the collagen region of surfactant proteins A1 (SP-A1) and A2 (SP-A2) and mannose binding lectin (MBL). RESULTS: The T allele at T1492C and G allele at G1649C of SP-A2 were observed at slightly higher frequencies in ABPA patients (86% and 93%) than in controls (63% and 83%), and the C alleles at position 1492 and 1649 were found in higher frequencies in CCPA patients (33% and 25%) than in ABPA patients (14% and 7%) (all p>0.05). However, the CC genotype at position 1649 of SP-A2 was significantly associated with CCPA (chi(2)=7.94; p(corr)< or =0.05). Similarly, ABPA patients showed a higher frequency of the TT genotype (71%) at 1492 of SP-A2 than controls (43%) and CCPA patients (41%) (p>0.05). In the case of MBL, the T allele (OR=3.1, range 1.2-8.9; p< or =0.02) and CT genotype (chi(2)=6.54; p(corr)< or =0.05) at position 868 (codon 52) were significantly associated with CCPA, but not with ABPA. Further analysis of genotype combinations at position 1649 of SP-A2 and at 868 of MBL between patient groups showed that both CC/CC and CC/CT SP-A2/MBL were found only in CCPA patients, while GG/CT SP-A2/MBL was significantly higher in CCPA patients in comparison to ABPA patients (p< or =0.05). SNPs analysed in SP-A1 did not differ between cases and controls. CONCLUSIONS: Distinct alleles, genotypes and genotype combinations of SP-A2 and MBL may contribute to differential susceptibility of the host to CCPA or ABPA.     

慢性丙型肝炎病毒感染者甘露糖结合凝集素基因多态性研究

目的研究丙型肝炎病毒（HCV）感染者甘露糖结合凝集素（MBL）基因多态性。方法应用序列特异性引物PCR法（PCR-SSP）方法检测甘肃地区汉族150例慢性丙型肝炎及75例健康对照者MBL第一外显子（EXONⅠ）52、54、57位基因型。结果甘肃地区汉族人群MBL基因EXONⅠ的52,57位没有检测出突变体,而54位基因在HCV感染者和在正常对照者中的基因型频率和基因频率比较差异均无统计学意义（P〉0.05）;丙氨酸转氨酶（ALT）〉80U/L、ALT〈40U/L两组基因型频率和等位基因频率比较差异均有统计学意义（P〈0.05）;HCV-RNA定量中、高载量组与低载量组MBL-54位基因型频率和基因频率比较差异也均有统计学意义（P〈0.05）。结论 HCV感染者MBL的EXONⅠ54位基因多态性与慢性HCV感染无显著相关性,而54位等位基因与ALT的升高和HCV-RNA载量有一定的相关性。     

The Role of Mannan-Binding Lectin (MBL) Gene Polymorphism in Ulcerative Colitis

Series studies suggest that enteropathogenic microorganisms play a substantial role in the clinical initiation and relapses of ulcerative colitis (UC). Mannan-binding lectin (MBL) is an important constituent of the innate immune system, and deficiency of MBL has been reported to increase the overall susceptibility of an individual to infectious disease. This study was aimed to investigate the associations between polymorphisms of the MBL gene and UC. Recruited in this study were 108 Japanese patients with UC and 144 healthy control subjects. Polymorphism at codon 54 of exon 1 of the MBL gene was investigated by polymerase chain reaction based restriction fragment length polymorphism. In general, no significant difference in MBL polymorphism was found between UC patients and health controls. However, the frequency of A carriers was significantly higher in the relapsing cases than controls (Odds ration = 2.19, 95%CI, 1.10–4.34; p = 0.023), and similar tendency was also found in A/A genotype. In conclusion, the polymorphism at codon 54 of exon 1 of the MBL gene associated with the susceptibility to the relapsing phenotype of ulcerative colitis. It suggests that codon 54 A variants of MBL gene may have an increased risk for the flare-ups of UC.     

甘露糖结合凝集素水平的调节与肺结核易感性关系的研究

目的研究甘露糖结合凝集素(MBL)水平的调节与肺结核易感性的关系。方法对142例肺结核患者和120例健康对照者血清中MBL水平进行测定。同时采用限制性片段长度多态性分析方法对MBL2基因多态性进行测定。结果采用单因素方差分析不同基因型组的MBL水平,YA/YA组,XA/YA组和XA/XA、YA/YB、XA/YB、YB/YB组,发现3组之间和任何两组之间的MBL水平差异均有统计学意义(P0.01)。肺结核患者MBL水平显著高于健康对照(P0.01)。健康对照者中携带YA/YA基因的个体中有93.2%(55/59)的MBL水平大于1 000ng/mL。而携带XA/XA或B等位基因的个体100%(26/26)的MBL水平小于或等于1 000ng/mL。结论 MBL水平可能与肺结核易感性有关,而决定高水平MBL的YA/YA基因可能是一种保护性基因。     

Mannose-binding lectin polymorphisms in severe sepsis: relationship to levels, incidence, and outcome

Mannose-binding lectin (MBL) genetic polymorphisms result in deficiency of the encoded protein and increased susceptibility to infection, especially in children and the immunocompromised. The objective of this study was to investigate the relationship between MBL-2 exon 1 and promoter -221 polymorphisms, plasma levels of the encoded protein, and the incidence and outcome of severe sepsis and septic shock. One hundred seventy-four white adult patients with severe sepsis or septic shock were recruited in a prospective multicenter study across eight intensive care units in the South of England, UK. Genotype and haplotype frequencies were compared between normal population controls and patients, and between survivors and nonsurvivors. Plasma levels of encoded protein were related to genotype and outcome. The exon 1 polymorphisms (A/O or O/O) were significantly more common in the patients with severe sepsis and septic shock than in normal healthy adults (54.6% vs. 39.7%, P = 0.001), and there was a significant difference in haplotype frequency between controls and septic patients (P < 0.0001). There was no significant difference in MBL-2 genotype or haplotype frequency between survivors and nonsurvivors. There was a strong relationship between MBL-2 haplotype and plasma MBL concentration (P < 0.001). Individual plasma levels were variable and increased between days 1 and 7. The mortality rate was higher in those with MBL levels <1000 microg/L than in those patients with levels >1000 microg/L (47.2 vs. 22.2%, P = 0.05). We conclude that genetic polymorphisms resulting in mannose-binding lectin deficiency are associated with increased susceptibility to sepsis. The close relationship between polymorphic variants and plasma MBL concentration persists during sepsis but individual levels vary widely. Lower circulating MBL levels are associated with a poor outcome.     

Apolipoprotein(a) gene polymorphisms (TTTTA)n and G/A-914 affect Lp(a) levels in ischemic heart disease patients from Serbia

OBJECTIVES: Lipoprotein(a) (Lp(a)) concentration is determined primarily by the apolipoprotein(a) (apo(a)) gene. The pentanucleotide (TTTTA)n repeat and G/A-914 polymorphisms are in the 5' promoter region of the apo(a) gene. To elucidate whether these polymorphisms affect Lp(a) levels, a total of 211 Serbian adults were investigated. DESIGN: One hundred and eleven patients with ischemic heart disease and 100 healthy controls were genotyped and Lp(a) levels determined. RESULTS: Lp(a) concentrations differed according to the (TTTTA)n genotypes: among those having at least one allele 8, patients had significantly higher Lp(a) values than controls. A decreasing trend of Lp(a) values was associated with the -914A allele in controls but the opposite was true in patients. Patients with genotype TTTTA allele 8/AA-914 had significantly higher Lp(a) values than those without allele 8/AA (p < 0.05). The >8>8/GG genotype was not detected. Significant linkage disequilibrium between (TTTTA)n and G/A-914 polymorphism (p < 0.001) was found. In multivariate regression analysis, the G/A-914 polymorphism significantly (p < 0.05) affected Lp(a) levels in patients, after taking into account the (TTTTA)n polymorphism. CONCLUSION: These results indicate that (TTTTA)n and G/A-914 polymorphisms affect Lp(a) levels in ischemic heart disease as a consequence of the linkage disequlibrium.     

SORL1基因多态性与阿尔茨海默病关联分析

目的探讨SORL1基因多态性与阿尔茨海默病（Alzheimer disease,AD）是否存在关联。方法采用聚合酶链反应-限制性片段长度多态性（PCR—RFLP）技术,检测114例AD患者及111例健康对照者的SORL1基因多态性分布特征。结果AD组SORL1的rs12285364SNP,CT基因型频率显著高于对照组（27．2％vs16．2％,P〈0．05）;AD组TT基因型频率显著低于对照组（0vs4．5％,P〈0．05）。CT基因型与女性AD存在正关联（OR=3．100,95％CI=1．260～7．629）,而与男性AD的关联无统计学意义。结论CT基因型可能与AD有关,此种关联主要影响女性。