MBL2基因P54位点多态性与结核易感性相关性的Meta分析

目的应用Meta的分析方法探讨甘露聚糖结合凝集素2(mannose-binding lectin 2,MBL2)基因P54位点多态性与结核易感性的关系。方法用计算机检索万方、CNKI、PubMed、CBM、EMbase等数据库,查找国内外从建库至2016年5月20日公开发表的所有关于研究MBL2基因多态性与肺结核易感性关系的相关文献。由两名评价者根据其纳入与排除标准筛选文献,提取并评价文献资料,最后采用RevMan5.2软件及STATA 10.0软件进行Meta分析。结果最终共纳入21个病例对照研究,其中包括结核组4 745例,对照组5 379例,经异质性检验,各研究之间存在统计学异质性(P0.1),故总体分析采用随机效应模型Meta分析结果显示:对于总体人群而言,MBL2基因P54位点与结核易感性关联差异无统计学意义(OR=1.08,95%CI=0.92~1.26,P=0.35);同时,在亚洲人群中MBL2基因P54位点与结核易感性关联差异无统计学意义(OR=1.18,95%CI=0.99~1.41,P=0.07);在高加索人群中MBL2基因P54位点与结核易感性关联差异无统计学意义(OR=0.83,95%CI=0.63~1.09,P=0.18);在非洲人群中MBL2基因P54位点与结核易感性关联差异无统计学意义(OR=0.80,95%CI=0.55~1.18,P=0.26)。结论 MBL2基因P54位点多态性与结核的发病风险可能不存在相关性。     

ApoA5-1131T/C基因多态性与维吾尔族2型糖尿病的关联研究

[目的]探讨载脂蛋白A5(Apolipoprotein A5,ApoA5)-1131T/C基因多态性与维吾尔族2型糖尿病及体内脂质谱的关系.[方法]依据病例一对照设计方法,采用全自动生化分析仪等技术测定维吾尔族体内脂质谱;应用PCR-RFLP法对维吾尔族的54例2型糖尿病患者、54例糖耐量异常患者和108名正常人ApoA5-1131T/C基因多态性进行分析. [结果]3组人群的ApoA5-1131T/C位点基因型和等位基因频率比较均无统计学意义.3种基因型的TG比较差异有统计学意义(P=0.046),C等位基因的TG高于T.Ligistic回归分析显示与2型糖尿病密切相关的独立危险因素依次是TG(P=0.001)和腰围(P=0.027).[结论]ApoA5-1131T/C基因多态性与新疆维吾尔族2型糖尿病不具有相关性,但与TG水平相关.     

MBL基因多态性与多发性骨髓瘤患者诱导化疗期间感染的关联

目的 分析甘露聚糖结合凝集素(MBL)基因多态性与多发性骨髓瘤(MM)诱导化疗期间感染的关联。方法 选择2017年12月—2019年12月于武汉市中西医结合医院行诱导化疗的MM患者137例,根据诱导化疗期间是否发生感染分为感染组79例和非感染组58例,采用聚合酶链式反应限制性片段长度多态性(PCR-RFLP)法检测MBL基因位点单核苷酸多态性,采用酶联免疫吸附测定法检测血清MBL含量水平。结果 感染组MBL基因rs11003125位点H/H、H/L基因型频率及H、L等位基因频率与非感染组比较,差异有统计学意义(P<0.05);感染组MBL基因rs1800450位点A/A、A/B基因型频率及A、B等位基因频率与非感染组比较,差异有统计学意义(P<0.05);Logistic回归分析法结果显示,MBL基因启动子区rs11003125(H-550L)位点H/H基因型、外显子区rs1800450(A+230B)位点A/A基因型是MM诱导化疗期间感染的保护因素(P<0.05);两组患者MBL基因rs11003125位点、rs1800450位点不同基因型血清MBL含量水平比较,差...     

新疆维、汉两民族非综合征性唇腭裂IRF6基因多态性分析

目的:探讨非综合征性唇腭裂(NSCL/P)干扰素调节因子6(IRF6)rs2013162位点单核苷酸多态性(SNP)在新疆维、汉两民族内和民族间基因型和等位基因型的频率差异。方法:抽取100例NSCL/P患者作为NSCL/P组(维吾尔族50例、汉族50例),对照组100例(维吾尔族50例、汉族50例),运用聚合酶链式反应-限制性片段长度多态性(PCR-RELF)技术来分析IRF6基因的多态性,病例-对照研究分析两组基因型和等位基因型频率及两民族内和民族间频率的差异。结果:rs2013162位点GG基因型和等位基因G和T频率在NSCL/P组和对照组中分布差异有统计学意义(P<0.05),维、汉两民族内rs2013162位点维吾尔族中GG和TT基因型及等位基因G和T分布差异有统计学意义(P<0.05),维、汉两民族间rs2013162位点NSCL/P组中维吾尔族GG和TT基因型和等位基因G的频率均高于汉族,两民族间基因型和等位基因型分布差异均无统计学意义(P>0.05)。结论:新疆维、汉族NSCL/P与rs2013162位点GG基因型及等位基因G存在相关性。     

MPO和NAT2基因多态性与成人急性白血病易感性

目的研究髓过氧化物酶（MPO）和N-乙酰基转移酶2（NAT2）基因多态性与成人急性白血病易感性的关系.方法用1∶1配对病例-对照研究方法,收集成人急性白血病患者和对照各139例,应用聚合酶链-内切酶片段（PCR-RFLP）方法分析病例组和对照组MPO和NAT2的基因多态性,比较不同基因型与成人急性白血病易感性.结果 MPO-463A等位基因分布频率病例组低于对照组,MPO（G-463A）各基因型在病例组与对照组中的分布差异有统计学意义（χ^2=7.026,P〈0.05,OR=0.505,95%CI=0.325～0.847）.NAT2乙酰化表型频率在病例组与对照组的分布差异无统计学意义（χ^2=2.260,P〉0.05）;但NAT2＊5 481T等位基因和NAT2＊6 590A等位基因分布频率病例组高于对照组（P〈0.05）.结论 MPO与成人急性白血病易感性相关,携带MPO（G-463A）突变基因型（GA/AA）个体可降低白血病的发病风险;NAT2乙酰化表型可能与白血病的易感性无关,但NAT2＊5（C481T）、NAT2＊6（G590A）单核苷酸突变频率病例组明显高于对照组.     

DAT13’端VNTR区多态性与异常体液型癌症的相关性研究

目的探讨多巴胺转运体基因1(DAT1)3’端40bp VNTR多态性与新疆省维吾尔族异常体液型癌症的相关性。方法按维吾尔医将癌症患者分为4种体液型,采用聚合酶链式反应(PCR)和VNTR多态性分析技术对新疆省维吾尔族47例异常黑胆质型癌症患者、26例其它异常体液型癌症患者和57例正常对照组DAT1多态性进行检测,比较各组间等位基因和基因型频率分布的差异。结果(1)所测人群中,DAT1 VNTR多态性表现出6～11倍重复的6种等位基因,其中最为常见的等位基因为10倍重复的480bp片段,其基因频率为90.4%。共检出6种基因型,其中最常见的基因型为480bp/480bp,占80.7%。(2)DAT1 VNTR10倍重复等位基因及10/10基因型个体患异常黑胆质型癌症的发病风险与非10倍重复等位基因和非10/10基因型个体差异无统计学意义(P=0.158,OR=1.994,95%CI为0.754～5.275;P=0.138,OR=2.143,95%CI为0.772～5.947);异常黑胆质型癌症患者和其它异常体液型癌症患者的DAT1 VNTR等位基因及基因型频率的差异均无显著性(P=0.729;P=0.782)。结论DAT13’端40bp可变串联重复多态性可能与维吾尔医异常体液型癌症易感性无关。     

脂蛋白脂酶基因Hind Ⅲ酶切多态性与维吾尔族2型糖尿病及体内脂质谱的关联研究

目的 探讨脂蛋白脂酶(LPL)基因HindⅢ酶切多态性与维吾尔族2型糖尿病及其体内脂质谱的关系.方法 依据病例-同胞对照设计方法,采用全自动生化分析仪等技术测定维吾尔族人群体内脂质谱;应用聚合酶链反应-限制性内切酶长度多态性(PCR-RFLP)方法,对维吾尔族62例2型糖尿病患者、62例糖耐量受损者和124名正常人LPL基凶HindⅢ酶切多态性进行分析.结果 三组人群的LPL基因的基因型分布和等位基因频率均无统计学意义.H+H+组、H-H-组、H+H-组的TG水平分别为(2.26±1.35)、(1.73±1.31)、(1.80±0.95)mmol/L,三种基因型与体内脂质等指标比较,突变型H+H+组的TG明显大于其他各组.多因素Logistic回归分析显示,TG(P=0.034)和腰围(P＝0.001)是2型糖尿病独立危险因素.结论 LPL基因HindⅢ酶切多态性与新疆维吾尔族人群2型糖尿病的危险性并无统计学上的相关性,LPL基因突变可能是引起血浆TG水平升高的因素之一.     

芳烃受体基因多态性与成人急性白血病易感性关系的病例-对照研究

[目的]探讨芳烃受体AHR基因多态性与成人急性白血病遗传易感性的关系.[方法]采用1：1配对病例-对照研究的方法,应用PCR-RFLP和AS-PCR技术,分析与比较了136对汉族成人急性白血病病例与对照的芳烃受体基因1549C→T,1661G→A,1708G→A 3个位点的基因多态性,及AHR基因多态性与成人急性白血病易感性的关系.[结果]AHR 1549C→T和1708G→A位点的突变基因型在对照组与病例组中都为0;AHR1661G→A位点A突变等位基因在对照组和病例组中的分布频率分别为33%和43%,差异有显著性（X2=5.261 9,P=0.021 8,OR=1.501 4,95%CI：1.060 2～2.126 2）;AHR 1661G→A位点A突变基因型（A/A＋G/A）频率在病例与对照组间的分布差异有显著性（X2=10.852 6,P=0.001 0,OR=2.260 1,95%CI：1.386 5～3.684 2）;按性别分层可见该差异主要存在于女性（X2=11.756 5,P=0.006 0,OR=3.607 8,95%CI：1.708 8～7.617 2）.[结论]AHR可能是成人急性白血病的易感基因,携带AHR 1661位点突变基因型（A/A＋G/A）者可能增加成人急性白血病、尤其是女性急性白血病的危险性.     

新疆哈萨克族食管癌与HLA-G基因多态性

目的 研究免疫相关基因HLA-G多态性与新疆哈萨克族食管癌易感性的关系.方法 采用病例-对照研究方法,调查新疆哈萨克族食管癌患者132例和非食管癌患者254例,应用聚合酶链反应(PCR)技术和聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术分别对HLA-G基因14bp缺失(rs16375)和HLA-G0105N(rs41557518)多态性进行检测,并比较2个位点不同基因型与食管癌发病风险的关系.结果 rs16375位点基因型为+14 bp/+14 bp、-14 bp/+14 bp、-14 bp/-14 bp;病例组与对照组的基因型及等位基因频率分布差异有统计学意义(χ2=7.54,P=0.02;χ2=6.80,P=0.01);携带-14bp/-14bp基因型的个体发生食管癌的危险性是+14 bp/+14 bp基因型的2.69倍(OR=2.69,95%CI=1.30～5.55);rs41557518位点基因型为C/-、C/C、-/-;病例组与对照组的基因型及等位基因频率分布差异无统计学意义(χ2=1.19,P=0.28;χ2=1.13,P=0.29);同时携带基因型-14bp/-14bp和C/C的个体发生食管癌的危险性是同时携带基因型+14bp/+14bp和C/C个体的2.82倍(OR=2.82,95%CI=1.32～6.04).结论 HLA-G基因14bp缺失(rs16375)多态性与哈萨克族食管癌发生有关.     

维吾尔族人群LPL基因PvuⅡ多态性与身体测量和血生化指标的相关性研究

目的探讨脂蛋白脂酶(lipoprotein lipase,LPL)基因PvuⅡ酶切位点多态性在塔克拉玛干沙漠腹地健康维吾尔族人群中的分布特征及其与身体测量和血生化指标的相关性,并与不同种族人群进行比较。方法采用PCR-RFLP方法检测99例健康维吾尔族人群(男性38例,女性61例)LPL基因PvuⅡ酶切位点的多态性。结果新疆99例健康维吾尔族人群中以P+等位基因多见,频率(52.02%)高于P-等位基因频率(47.98%),三种基因型中以P+P-基因型最为多见(61.62%),其次为P+P+基因型(21.21%),最低是P-P-基因型(17.17%),且各基因型和等位基因频率在男女中分布无显著性差异(P0.05);男性中P-P-基因型组空腹血糖水平显著高于P+P+和P+P-基因型组,各基因型与空腹血糖有显著性差异(χ~2=3.411,P0.05),在女性中P-P-基因型组总胆固醇水平显著高于P+P-和P+P+基因型组,各基因型与总胆固醇有显著性差异(χ~2=4.669,P0.05),其他各项身体测量和生化指标均未见显著性差异(P0.05);而LPL基因PvuⅡ酶切位点多态性在维吾尔族人群中的分布与海南汉族人群、大连汉族人群、郑州汉族人群、海南黎族人群等不同民族人群比较均存在显著差异(P0.01,P0.05);与日本、中国汉族、韩国、阿拉伯、土耳其等不同种族人群比较也均存在显著差异(P0.01,P0.05),而与芬兰和印度人群比较的差异无显著性(P0.05)。结论 LPL基因PvuⅡ酶切位点P-P-基因型和P+等位基因在健康维吾尔族人群中的分布可能与空腹血糖、总胆固醇等血脂水平相关联。     

中国汉族人群结核易感基因多态性与耐药结核病相关性研究

目的 了解结核易感基因SLC11A1基因、VDR基因、MBL基因以及IFNG基因多态性在中国汉族人群敏感和耐药结核病患者中的分布,探讨其与耐药结核病发生的相关性.方法 使用焦磷酸测序法、Real-time探针法、SNaPshot法测定229例敏感肺结核(敏感组)和230例耐药肺结核(耐药组)患者的VDR基因、SLC11A1基因、MBL基因、IFNG基因的单核苷酸多态性(SNP).结果 VDR基因多态性位点在敏感组和耐药组间差异均无统计学意义(P＞0.05).SLC11A1基因的INT4位点基因型和等位基因频率在敏感组和耐药组间差异有统计学意义(P值分别为0.031、0.046);INT4位点在隐性遗传模型假定下,敏感组和耐药组间差异具有统计学意义(OR=5.756,95%CI:1.261～26.269,P=0.011),结合该位点各种组合下的OR值间的数量关系,确定该位点的遗传模型符合隐性遗传模型.MBL基因Q/P位点基因型和等位基因频率在敏感组和耐药组间差异有统计学意义(P值分别为0.029、0.033);在隐性遗传模型假定下,MBL基因Q/P位点基因型和等位基因频率在不同组别间差异有统计学意义(OR=9.290,95%CI:1.167～73.949,P=0.011).IFNG基因的多态性位点在敏感组和耐药组之间的分布无统计学意义.结论 SLC11A1基因的INT4位点和MBL基因Q/P位点可能与中国汉族人群耐药结核病的发生具有一定的相关性.

Abstract：

Objective To investigate the distribution of polymorphisms of SLC11A1 gene,VDR gene,MBL gene and IFNG gene with susceptibility to tuberculosis (TB) in Chinese Han population suffering from drug-sensitive TB and drug-resistant TB so as to identify the correlation between gene polymorphisms and the development of drug-resistant TB.Methods Single nucleotide polymorphisms (SNP) of VDR gene,SLC11A1 gene,MBL gene,IFNG gene were typed and analyzed by pyrosequencing,Real-time Probe and SNaPshot among 229 patients with drug-sensitive TB and 230 patients with drug-resistant TB.Results The polymorphic foci of VDR gene from the drug-sensitive TB group and the drug-resistant TB group showed no significant difference (P＞0.05).The genotype of INT4 site and allelic frequency of SLC11A1 gene for drug-sensitive TB group were significantly different from those for drug-resistant TB group(P=0.031,0.046).If recessive inheritance was assumed,the genotypes of INT4 site from the two groups were significantly different (0R=5.756,95% CI:1.261-26.269,P=0.011).Considering the relationship between OR values under various combination,our findings confirmed that the genetic mode of INT4 site was in accordance with recessive inheritance.The genotypes of Q/P site and allelic frequencies of MBL gene from drug-sensitive and drug-resistant groups were significantly different (P=0.029,0.033).The difference still existed under the hypothesis of recessive inheritance (OR=9.290,95% CI:1.167-73.949,P=0.011).The polymorphic foci of IFNG gene from the two groups showed no significant difference.Conclusion INT4 sites on SLC11A1 gene and Q/P site on MBL gene were probably associated with the development of drug-resistant TB in Chinese Han population.Further study on this issue would be helpful in locating the population at high risk of drug-resistant TB and exploring the effective intervention to decrease the incidence of this disease.     

Association between -221 X/Y polymorphism of mannose-binding lectin (MBL) gene and susceptibility to HTLV-1 infection among people from an endemic region in the Northeast of Iran

BackgroundThe role of (MBL) gene single nucleotide polymorphisms (SNPs) has been well documented in susceptibility to several infectious diseases. This study aimed to investigate the association between two MBL promoter variants, -550 H/L and -221 X/Y, and susceptibility to HTLV-1 infection.MethodsA total of 153 subjects infected with HTLV-1 and 169 healthy controls were recruited. SSP-PCR method was applied to genotype -550 H/L and -221 X/Y polymorphisms. Associations between genotypes or alleles and susceptibility to HTLV-1 infection were analyzed by Pearson's Chi-Square. p ≤ .05 was considered statistically significant.ResultsStatistical analysis revealed significant differences between the two groups in the -221 position (χ2 = 19.709; p = .000). The MBL YX genotype was significantly associated with increased susceptibility to HTLV-1 (OR = 2.73, %95 CI = 1.74–4.30). Combined genotype of the two loci showed that the HYHX genotype (OR = 2.20, 95% CI = 1.95–2.48) and LYLX (OR = 1.97, 95% CI = 1.13–3.45) were associated with an increased risk of HTLV-1 infection.ConclusionOur results represent the importance of -221 X > Y variants in acquisition of HTLV-1 as this is the case for several other viral and bacterial infections.     

MBL2 gene polymorphisms and susceptibility to tuberculosis in a northeastern Brazilian population

The innate immune system represents the first line of host defense against pathogens. Genetics factors regulating the immune responses play a role in the susceptibility to infectious diseases, such as tuberculosis (TB). We analyzed MBL2 promoter and exon 1 functional single nucleotide polymorphisms (SNPs) in a group of 155 TB patients and 148 healthy controls in order to evaluate their influence on the onset of infection and TB development. There was no association between MBL2 −550 HL promoter polymorphisms and susceptibility to develop TB, but heterozygous −221 Y/X genotype was significantly more frequent in pulmonary TB patients than controls. Moreover, MBL2 exon 1 O allele, was significantly associated with susceptibility to TB development in general (p = 0.023, OR = 1.61, 95% CI 1.05–2.49) and pulmonary TB (p = 0.0008, OR = 2.16, 95% CI 1.35–3.46); C allele at codon 57, as well as A/C genotype, were significantly more frequent in TB patients than in controls. Our results indicate that MBL2 polymorphisms, especially at codon 57, could be considered as risk factors for TB development.     

输尿管软镜碎石术后感染并发尿源性脓毒症与HLA-DRB1及MBL2基因多态性的相关性

目的探究人白细胞抗原(HLA)DRB1及甘露糖结合凝集素(MBL)基因多态性与输尿管软镜碎石术后感染并发尿源性脓毒症的相关性。方法选择2017年3月-2020年2月绍兴市中心医院收治的30例输尿管软镜碎石术后感染并发尿源性脓毒症及50例进行输尿管软镜碎石手术无术后感染患者作为研究对象,检测HLA-DRB1及MBL2基因多态性,分析其与输尿管软镜碎石术后感染并发尿源性脓毒症易感性的关系。结果HLA-DRB1基因0101-1102、1501-1502、1601-1602、0701-0702、0801-0806、0301-0302、0301、1001位点及MBL2基因rs2120131、rs4935047、rs7095891位点基因频率均符合哈-温平衡;HLA-DRB1基因1601-1602位点、0301-0302位点及MBL2基因rs7095891位点与脓毒症发生相关(P<0.05)。脓毒症组患者1601-1602位点在显性模型、加性模型下与脓毒症相关(P<0.05);0301-0302位点在显性模型下与脓毒症相关(P<0.05);MBL2基因rs7095891位点在加性模型下与脓毒症发生相关(P<0.05)。Logistic多因素分析示,合并糖尿病、HLA-DRB1基因1601-1602位点及MBL2基因rs7095891位点多态性是脓毒症发生的影响因素(P<0.05)。结论 HLA-DRB1及MBL2基因多态性与输尿管软镜碎石术后感染并发尿源性脓毒症易感性相关,临床可通过检验患者基因多态性评估脓毒症发生风险。     

The role of Mannose-binding lectin in leprosy: A systematic review

Leprosy is an infectious disease that may present different clinical forms depending on host immune response to Mycobacterium leprae. Mannose-binding lectin (MBL) is an acute phase protein associated with the pathophysiology of leprosy. Some studies have shown that there is a correlation between serum levels of MBL and polymorphisms in its gene associated with susceptibility per se and to different clinical forms. The aim of this study was to conduct a systematic review of publications in the literature that studied the association of MBL with leprosy. Databases were searched until December 2020 (PROSPERO: CRD42020158458), and additional searches were conducted scanning the reference lists of the articles. Two independent reviewers assessed the study quality using the Newcastle-Ottawa Quality Assessment Scale. Finally, 10 eligible articles were included in the study. The overall results indicated that both low MBL serum levels and polymorphisms in the structural or promoter region of its gene seem to be associated as protective factors against the development of severe forms. The results suggest that MBL may play a role in the clinical progression of leprosy.     

自然抗性相关巨噬细胞蛋白1基因多态性与肺结核易感性的研究

目的　探讨自然抗性相关巨噬细胞蛋白 1基因 (NRAMP1)多态性与中国汉族人群肺结核发病的关系。方法　采用以医院为基础的病例对照研究设计 ,用聚合酶链反应 限制性片段长度多态性分析 (PCR RFLP)法检测NRAMP1基因中INT4、D5 4 3N及 3′UTR 3个多态性位点的基因型 ,并对结核病相关危险因素进行问卷调查 ,应用SPSS软件进行单因素和多因素非条件logistic回归分析。2 0 0 1年 4月至 2 0 0 2年 6月选择 110例肺结核病例 ,平均年龄为 (2 8± 13)岁 ;对照组为 180名健康体检者 ,平均年龄为 (2 7± 9)岁。对NRAMP1基因各多态性位点进行单因素分析。结果　病例组D5 4 3NG/A及 3′UTRTGTG +/del基因型频率显著高于对照组 ,OR值 (95 %CI)分别为 2 2 2 (1 0 3～ 4 78)和 1 93(1 14～ 3 2 6 )。病例组和对照INT4各基因型频率比较差异无显著性。多因素分析调整暴露史和疫苗接种史 2个因素后 ,D5 4 3NG/A及 3′UTRTGTG +/del基因型仍与结核病显著相关 ,调整OR值 (95 %CI)分别为 3 0 4 (1 12～ 8 2 7)和 2 36 (1 2 0～ 4 6 4 ) ,而病例和对照组INT4位点多态性比较差异未见显著性。结论　NRAMP1基因D5 4 3N及 3′UTR位点多态性可能是汉族人群肺结核的易感因素。     

NRAMP1基因INT4和3’UTR位点多态性与肺结核易感性的研究

目的 探讨人类自然抵抗相关巨噬细胞蛋白1（NRAMP1）基因INT4和3＇UTR位点多态性与中国北方汉族成人肺结核发病的关系.方法 采用1：1配对的病例对照研究设计,用聚合酶链反应-限制性片段长度多态性分析方法检测NRAMP1基因中INT4和3＇UTR两个多态性位点,对与肺结核相关的危险因素进行问卷调查,进行单因素和多因素条件logistic回归分析,同时对基因型与肺结核病变的性质和程度进行研究.结果 对124对研究对象进行了INT4和3＇UTR两个多态性位点的基因分型,3＇UTR TGTG＋/del基因型病例组频率显著高于对照组,粗OR值（95%CI）为2.923（1.557～5.487）.病例组和对照组INT4各基因型频率比较差异均无统计学意义.对17个环境危险因素进行了单因素分析,在多因素分析中调整卡痕、体重指数、人均居住面积、家族史4个因素后,3＇UTR TGTG＋/del基因型仍与肺结核显著相关,调整OR值（95%CI）为2.955（1.369～6.381）.在INT4不同基因型中,病例组和对照组肺结核病变性质差异具有统计学意义（x2=9.634,P＜0.05）.结论 NRAMP1基因3＇UTR位点多态性可能是中国北方汉族成人肺结核的易感因素,而INT4多态性可能与肺结核的病变性质有关系.     

Association between SLC11A1 polymorphisms and susceptibility to different clinical forms of tuberculosis in the Peruvian population.

Polymorphism in SLC11A1 has been implicated in host susceptibility to tuberculosis. We have studied associations between INT4, D543N, and 3'UTR polymorphisms of SLC11A1 and different clinical forms of TB. Analysis used 507 patients with pulmonary TB, 123 with extra pulmonary TB and 513 controls. INT4 and D543N showed allelic association with pulmonary TB (P=0.02 and 0.03 respectively). INT4-D543N-3'UTR haplotypes showed an association with pulmonary TB (P=0.03). No association of SLC11A1 with miliary TB was observed, and a possible association of D543N to the pleural form (P=0.08) was suggested. These results support association between SLC11A1 and TB, particularly to the common pulmonary form.     

The -137G/C single nucleotide polymorphism in IL-18 gene promoter contributes to tuberculosis susceptibility in Chinese Han population

BackgroundInterleukin (IL) -18 is crucial to host defense against mycobacterial infections. Recent studies have indicated IL-18 gene polymorphisms are associated with susceptibility to several clinical diseases.ObjectiveThe aim of this study is to investigate the association of IL-18 (-137G/C and -607C/A) gene promoter single nucleotide polymorphisms (SNPs) with susceptibility to tuberculosis (TB), and the effects of those SNPs to its protein producing capacity in Chinese Han population.Methods407 TB patients (including 113 children and 294 adults) and 469 healthy volunteers (including 167 children and 302 adults) from Chinese Han population were enrolled. The IL-18 gene promoter polymorphisms at positions of − 137 and − 607 were determined by sequence specific primer-polymerase chain reaction (SSP-PCR). The IL-18 levels in the supernatants of PBMCs from 46 healthy volunteers were measured by ELISA.ResultsThe gene distribution of IL-18 -137G/C and -607C/A showed none difference between adult and pediatric population. The frequency of IL-18 -137GG genotype was significantly higher in total TB group than that in total healthy control group (79.1% V 69.3%, P < 0.01), while the frequencies of GC genotype and C allele were conversely lower (19.2% V 27.9%, P < 0.01; 11.3% V 16.7%, P < 0.01 respectively). The difference of the -137CC genotype distribution between patients and controls was not observed. At the -607C/A polymorphic site, patient and control groups had a very similar gene distribution. Isolated PBMCs with IL-18 -137GC/CC genotype were able to produce a higher level of IL-18 than those with IL-18 -137GG genotype, either spontaneously or in response to PMA plus calcimycin A23187.ConclusionIL-18 -137G/C polymorphism contributed to TB susceptibility in Chinese Han population. Allele G might be a predisposing gene of TB, while allele C probably plays a role in preventing mycobacterium tuberculosis infection by promoting more vigorous protein expression.     

蒙古族与回族人群甘露糖结合凝集素基因启动子单体型分析

目的分析内蒙古自治区蒙古族人群和宁夏回族自治区回族人群甘露糖结合凝集素（MBL）基因启动子区和5’端非翻译区的单核苷酸多态性（SNP）及其单体基因型。方法MBL基因SNP分析采用序列分析法；遗传学分析采用SHEsis软件。结果79例蒙古族人群中启动子-550位点H／H、H／L和L／L型分别占38．0％、45．6％和16．5％，等位基因变异频率为0．392；-221位点Y／Y和X／Y型分别占81．0％和19．0％，等位基因突变频率为0．095。69例回族人群中启动子一550位点H／H、H／L和L／L型分别占36．2％、44．9％和18．8％，等位基因变异频率为0．413；-221位点Y／Y和X／Y型分别占75．4％和24．6％，等位基因突变频率为0．123。启动子单体型有HYP、LYP和LXP3种，在蒙古族人群中的频率分别为0．608、0．297和0．095；回族人群中的频率分别为0．587、0．290和0．123。所有样本5’端非翻译区＋4位点均无突变即均为P型。蒙古族和回族-550位点和-221位点的变异频率差异无统计学意义（χ^2-550=0．131，P=0．718；χ^2-221=0．610，P=0．435）。结论（1）本研究中蒙古族和回族人群启动子单体型仅HYP、LYP和LXP3种。（2）启动子区-550位点的变异频率较高，-221位点变异频率较低，＋4位点无SNP发现。两组人群上述位点的变异频率差异无统计学意义。