血清、脑脊液肿瘤坏死因子-α水平及其-308G/A基因多态性与多发性硬化的相关性

目的研究中国广东汉族人群中血清、脑脊液(cerebrospinalfluid,CSF)肿瘤坏死因子-α(tumornecrosisfactor-α,TNF-α)水平及其-308G/A基因多态性与多发性硬化之间的相关性。方法采用双抗体夹心ABC-ELISA法测定68例无亲缘关系的急性发作期多发性硬化(multiplesclerosis,MS)患者和55例非免疫系统疾病患者的血清、CSF的TNF-α水平,同时应用聚合酶链反应-限制性片段长度多态性技术检测上述68例MS患者和106名无血缘关系的广东籍健康汉族人的TNF-α-308G/A基因型。结果发作期MS患者血清中TNF-α水平与非免疫系统疾病患者组间差异有统计学意义(P<0·05),分别是(276±71)pg/mL和(234±76)pg/mL;发作期MS患者CSF中TNF-α水平与非免疫系统疾病患者组差异无统计学意义(P>0·05),分别是(265±78)pg/mL和(245±83)pg/mL;TNF-α-308G/A各等位基因型频率在MS组和正常人组比较差异无统计学意义(P>0·05),MS组TNF-α基因AA基因型和A等位基因频率分别为4.4%和14·0%,正常人对照组分别为0和8.5%。结论(1)发作期MS与血清中TNF-α水平相关,与CSF中TNF-α水平不相关。(2)从目前调查的例数中,中国广东汉族人群TNF-α基因-308G/A多态性与广东人群中MS不相关。     

多发性硬化与遗传研究进展

多发性硬化与遗传因素关系的研究受到极大重视 ,关联基因多态性与 MS易感性及病情程度的研究获得了一些进展 ,连锁分析的结果也支持 MS是一种遗传性疾病 ,本文总结有关这两方面的研究进展     

肿瘤坏死因子-α脑脊液水平及其多态性与多发性硬化的相关性

目的研究中国南方汉族人群中脑脊液肿瘤坏死因子-α水平及其G-308A位点基因多态性与多发性硬化之间的相关性。方法采用双抗体夹心ABC-ELISA法测定68名无亲缘关系的急性发作期MS病人和55例非免疫系统疾病人的CSF(对照)TNF-α,同时应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术检测上述68例MS病人和106名无血缘关系的广东籍健康汉族人的TNF-α基因型。结果发作期MS患者CSF中TNF-α水平与正常对照组,无显著差异(P>0.05),分别是265±78pg/m l和245±83pg/m l;TNF-α各等位基因型频率在MS组和正常人组比较无显著差异(P均>0.05),病例组TNF-α基因A纯合基因型和A等位基因频率(分别为4.4%和13.9%),正常对照组(分别为0%和8.5%)。结论1.CSF中TNF-α水平与发作期MS患者无相关。2.中国南方汉族人群存在TNF-α基因G-308A位点突变。3.从目前调查的例数中,中国南方汉族人群TNF-α基因G-308A多态性与广东人群中MS及CSF中TNF-α水平无关。     

白介素-10基因多态性与感染性疾病的关系的研究进展

白介素-10(interluekin-10 IL-10)是一种具有抗炎和免疫调节作用的细胞因子。是同型二聚体细胞因子, 属长链细胞因子家族。现已发现B细胞、单核／巨噬细胞、肥大细胞、角化细胞、肝细胞及多种肿瘤细胞均可分泌IL-10。 IL-10通过调节其他细胞因子的作用而起到抗炎和免疫调节作用。我们在这里主要谈一下,IL-10的生物学特点及在IL- 10基因的启动子区域几个位点的基因多态性与感染性疾病的关系的研究进展。     

多发性硬化与遗传研究进展

多发性硬化与遗传因素关系的研究受到极大重视，关联基因多态性与MS易感性及病情程度的研究获得了一些进展，连锁分析的结果也支持MS是一种遗传性疾病，本文总结有关这两方面的研究进展。     

白介素-23受体基因多态性与乙肝相关肝细胞癌的易感性研究

目的:探讨白介素-23受体(IL-23R)基因多态性与广西壮族人群乙肝相关肝细胞癌(HCC)易感性的关系。方法:采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)对84例乙肝表面抗原(HBSAg)阳性HCC患者(病例组)和94例HbsAg阳性体检者(对照组)IL-23R基因rs10889677、rs1884444、rs114658173个位点的单核苷酸多态性进行检测及其部分标本进行直接测序鉴定。采用SHEsis软件构建IL-23R基因3个位点的单体型。Logistic回归分析IL-23R基因多态性和单体型与HCC遗传易感性的关系。结果:IL-23Rrs10889677、rs11465817位点的AA、AC、CC3种基因型和A、C两种等位基因在HCC组与对照组之间的分布差异无统计学意义(P>0.05)。rs1884444位点的TT、TG、GG三种基因型及T、G两种等位基因在病例组和对照组的频率分布差异均有统计学意义(P均<0.05),Logistic回归分析发现携带TG基因型的个体发生HCC的风险较携带TT基因型的个体增加(校正OR=2.20,95%CI=1.11～4.37)。单体型构建发现CGC、AGC、CTC、ATC、CGA、AGA、CTA、ATA等8种单倍体,病例组和对照组的AGC单倍体分布差异有统计学意义(P<0.05),AGC单倍体携带者发生HCC的风险明显增加(校正OR=2.71,95%CI=1.06～6.93)。结论:IL-23R基因rs1884444位点TG基因型可能是HCC发病的危险因子;乙肝背景下AGC单倍体携带者患HCC的风险增加2.71倍,可能是乙肝相关肝癌发病的危险因素。     

屋尘螨过敏性哮喘患者白介素-2和白介素-4血清水平及基因多态性

目的:检测分析屋尘螨过敏性哮喘患者白介素-2(IL-2)、IL-4血清水平及基因多态性。方法:首次诊断为屋尘螨过敏性哮喘患者73例(过敏性哮喘组),按其临床表现再分为急性发作期组(n=25)、慢性持续期组(n=23)和临床缓解期组(n=25),另选体检健康人群作为对照组(n=81)。采用ELISA检测各组血清IL-2、IL-4和屋尘螨特异性IgE(SIgE)水平,采用等位基因特异性PCR检测各组IL-2基因rs6534349和IL-4基因rs2227284的单核苷酸多态性(SNP)位点基因多态性。结果:血清IL-2水平在急性发作期组(170.58±29.08pg/ml)及慢性发作期组(179.45±45.34pg/m)均较对照组(227.45±43.34pg/ml)明显降低(P0.01);两组血清IL-4水平分别为98.45±28.85pg/ml和89.34±39.21pg/ml,均较对照组(68.41±30.01pg/ml)明显升高(P0.05);临床缓解期组血清IL-2和IL-4水平与对照组差异无统计学意义(P0.05)。血清SIgE水平在急性发作期组(21.27±2.96pg/ml)、慢性持续期组(19.45±10.38pg/ml)和临床缓解期组(18.34±4.21pg/ml)均明显高于对照组(8.90±4.00pg/ml)(P0.01)。SIgE水平变化与IL-2变化呈负相关(r=-0.421,P0.01),与IL-4变化呈正相关(r=0.522,P0.01)。基因多态性分析显示,过敏性哮喘组患者IL-2rs6534349中GG型明显低于对照组(P0.01),而IL-4rs2227284CC型明显高于对照组(P0.01)。结论:屋尘螨过敏性哮喘与其血清IL-2、IL-4水平及基因多态性具有一定关系。     

白介素-10与乙肝易感性相关性研究

细胞因子在抗病毒免疫中发挥着重要的作用。细胞因子的基因多态性能影响个体间细胞因子水平上的差异,从而导致个体间对于乙肝病毒感染免疫应答的差异,影响个体对乙肝病毒的易感性。该文主要评述白介素-10基因多态性与乙肝病毒感染的关系。     

抗原处理相关蛋白基因多态性及与多发性硬化的相关性

目的对广东地区汉族MS患者作抗原处理相关蛋白基因(TAP)分型,探讨这些基因与广东人群中MS遗传易感性的可能关系。方法采用PCR扩增阻碍突变系统(PCR-ARMS)法对30名无亲缘关系的MS的病人和95名无血缘关系的广东籍健康汉族人作TAP分型。结果TAPl-333、637位等位基因基因型在广东汉族MS组及NC组中均以I和D为主,TAP2-379、565、665等位基因基因型分别为:V-A-T;TAP1和TAP2各等位基因基因型频率在MS组和正常人组间无显著差异(P>0.05)。结论从目前调查的例数,广东人群中MS与TAP基因不关联。     

白介素-1遗传多态性和Alzheimer病

淀粉样前体蛋白基因、早老素 - 1基因、早老素 - 2基因的突变可导致家族性 Alzheimer病 (FAD)的发生 ,散发性Alzheimer病 (SAD)与许多遗传易感性基因相关 ,其中最常见的是载脂蛋白 E基因的 ε4等位基因。近来的研究表明 ,AD与白介素 - 1(IL- 1)基因多态性相关。IL- 1水平在 AD脑内增高 ,IL- 1的过表达与 β-淀粉样斑块形成有关 ,并与其他危险因素如高龄、头外伤等共同作用 ,促进 SAD的发生。研究表明 ,IL- 1在 AD的发生、发展过程中具有重要作用     

白细胞介素-18基因多态性与广西壮族系统性红斑狼疮的遗传易感性

目的 探讨白细胞介素-18(interleukin 18,IL-18)基因单核苷酸多态性与广西壮族系统性红斑狼疮(systematic lupus erythematosus,SLE)易感性之间的关系.方法 以115例SLE患者和160名健康对照者为研究对象,应用聚合酶链反应-限制性片段长度多态性和DNA测序的方法对IL-18基因-137G/C、-607C/A单核苷酸多态性进行基因分型.结果 IL-18基因-137G/C多态性在SLE组和正常人群中的分布差异无统计学意义(P>0.05),而IL-18基因-607C/A多态性在两组人群中的分布差异有统计学意义(P<0.05),等位基因频率的相对风险分析发现,-607 C等位基因携带者患系统性红斑狼疮的风险是-607A等位基因的1.619倍(OR=1.619,95%CI:1.150-2.281).联合基因型分析发现,IL-18的-137G/-607C等位基因频率在SLE组中显著高于对照组(P<0.05).-137G/-607C等位基因携带者显著增加了SLE的发病风险(OR=1.484,95%CI:1.056-2.087).结论 IL-18基因-607C/A多态性与SLE的发病具有相关性,其中-607 C等位基因可能是SLE的遗传易感基因.     

Association of interleukin-1 gene polymorphisms with multiple sclerosis: a meta-analysis

Background

Dysregulated levels of interleukin-1 (IL-1) were observed in patients with multiple sclerosis (MS). Previous studies have provided conflicting evidence implicating the IL-1 gene polymorphisms in MS risk.

Methods

A meta-analysis of 16 case–control studies involving 3,482 cases and 3,528 controls was conducted to evaluate this association.

Results

No association was found between the IL-1α ?889 (rs1800587), IL-1α +4,845 (rs17561), IL-1β ?511 (rs16944), IL-1β +3,953 (rs1143634), IL-1ra variable number tandem repeat (VNTR) polymorphisms and MS risk. However, in subgroup analyses for the IL-1ra VNTR polymorphism, we found that individuals carrying the 2 allele had a 32 % increased risk for bout-onset MS (relapsing remitting and secondary progressive MS) when compared to the LL homozygotes (OR = 1.32, 95 % CI = 1.06–1.66, P _z = 0.014).

Conclusion

Common variants in the IL-1 region are not associated with MS risk but our data suggest that the IL-1ra VNTR polymorphism might be associated with bout-onset MS subtype.     

CYP19基因多态性与子宫内膜异位症相关性的研究

目的 探讨CYP19基因多态性与中国河北省汉族育龄妇女Ⅲ、Ⅳ期子宫内膜异位症发病风险的关系.方法 采用聚合酶链反应限制性片段长度多态性方法检测102例Ⅲ、Ⅳ期子宫内膜异位症患者(病例组)与100例无子宫内膜异位症病史患者(对照组)CYP19基因115T/C、240A/G、1 531 C/T位点多态性.结果 CYP19基因115T/C的3种基因型TT、TC、CC在病例组的分布为91.18%、8.82%、0,在对照组为88.00%、11.00%、1.00%.T、C等位基因在病例组和对照组中的分布为95.59%、4.41%和93.50%、6.50%.两组比较差异无统计学意义(P＞0.05).CYP19基因240A/G的3种基因型AA、AG、GG在病例组中的分布为27.45%、49.02%、23.53%,在对照组为45.00%、41.00%、14.00%.A、G等位基因在病例组和对照组中的分布为51.96%、48.04%和65.50%、34.50%.两组比较差异有统计学意义(P＜0.05).CYP19基因1531 C/T的3种基因型CC、CT、TT在病例组中的分布为41.18%、47.06%、11.76%,在对照组分别为38.00%、42.00%、20.00%,两组间差异无统计学意义(P＞0.05).C、T等位基因在病例组和对照组中的分布为64.71%、35.29%和59.00%、41.00%.两组比较差异无统计学意义.结论 CYP19基因240GG基因型可能是Ⅲ、Ⅳ期子宫内膜异位症发生的危险因素.     

Association of CD22 gene polymorphism with susceptibility to limited cutaneous systemic sclerosis

Activating and inhibitory signal transducers, CD19 and CD22, have been substantially implicated both in human systemic sclerosis (SSc) and tight-skin mouse, a model for SSc. We previously showed that a single nucleotide polymorphism (SNP) in CD19 promoter region was significantly associated with increased CD19 expression level and with susceptibility to SSc. In the present study, we examined whether CD22 polymorphisms were associated with susceptibility to SSc. CD22 variations were genotyped in 126 Japanese patients with SSc [47 diffuse cutaneous SSc and 79 limited cutaneous SSc (lcSSc)] and 93 unrelated healthy controls. At the c.2304C > A SNP coding for a synonymous substitution in exon 13, A/A genotype was observed in six patients with SSc (4.8 %) but none in the controls (P=0.040). All six patients with A/A genotype belonged to the lcSSc subgroup (7.6%, P=0.008 vs controls). Surface expression level of CD22 tended to be lower in B cells from the patients with A/A genotype (n=5) as compared with C/A (n=7) or C/C (n=14) genotype (17% decrease, P=0.0032). Taken together with our previous observation on CD19 polymorphism, intrinsic difference in the expression level of CD19 and CD22 was suggested to play a causative role in a proportion of patients with lcSSc.     

Association of the HLA-G gene polymorphism with multiple sclerosis in a Polish population

In this study, three polymorphic sites in the HLA-G gene: −725C>G>T, −716T>G and 14bp_indel were genotyped. Significant differences were found between patients and controls in the alleles and genotypes for −725C>G>T and in three-point haplotypes. We observed also a significant difference in the age of disease onset between patients positive and negative for 14bp_ins. The results suggest that single nucleotide polymorphisms in the promoter of the HLA-G gene (mainly −725C>G>T), and 14bp_indel, or some genetic marker in tight linkage disequilibrium with them are associated with multiple sclerosis.     

FAAH levels and its genetic polymorphism association with susceptibility to methamphetamine dependence

The fatty acid amide hydrolase (FAAH) gene was involved in the modulation of reward and addiction pathophysiology of illicit drugs abuse, and its polymorphisms might be associated with risk of methamphetamine (METH) dependence. This study aimed to investigate the FAAH mRNA levels in peripheral blood mononuclear cells and plasma protein levels and to analyze the 385C/A polymorphism (rs324420) between METH-dependent patients and controls. The levels of FAAH mRNA in METH dependence were significantly lower than in controls (P < 0.001), however, its plasma protein underwent a significant ∼2-fold increase (P < 0.001). The A allele of the 385C/A polymorphism significantly increased the METH dependence risk (P < 0.001, odds ratio [OR] = 1.646, 95% confidence interval [CI] = 1.332–2.034). The carried A genotypes (AA, AC, and AA/AC) of 385C/A polymorphism also increased METH-dependence risks under a different genetic model (AA vs. CC: P = 0.017, OR = 2.454, 95%CI = 1.171–2.143; AC vs. CC: P < 0.001, OR = 1.818, 95%CI = 1.404–2.353; AC/AA vs. CC: P < 0.001, OR = 1.858, 95%CI = 1.444–2.319). The similar results were obtained after adjusting for age and sex. Unfortunately, we failed to find that any genotype of 385C/A polymorphism affected the mRNA or plasma protein levels in controls, respectively (P > 0.05). These data indicate that the FAAH may play an important role in the pathophysiological process of METH dependence, and the 385C/A polymorphism may be associated with METH dependence susceptibility in a Chinese Han population.     

Elevated serum levels of lysophosphatidic acid in patients with multiple sclerosis

A plethora of studies have shown that lysophosphatidic acid (LPA) is involved both in inflammation and T cell apoptosis evasion. The aim of this study was to measure the concentrations of LPA in serum of patients with multiple sclerosis (MS). Twenty MS patients along with 20 age–sex matched healthy individuals were recruited for this investigation. By employment of ELISA method, we demonstrated that MS patients had higher levels of LPA in serum than control group (P = 0.006). This study is the first report of LPA elevation in MS disease.     

Association of a common polymorphism in the promoter of UCP2 with susceptibility to multiple sclerosis

Uncoupling protein 2 (UCP2) is a member of the mitochondrial proton transport family that uncouples proton entry to the mitochondria from ATP synthesis. UCP2 expression levels have been linked to predisposition to diabetes and obesity. In addition, UCP2 prevents neuronal death and injury. Here we show that the common –866G/A promoter polymorphism is associated with susceptibility to multiple sclerosis (MS) in the German population. We analysed altogether 1,097 MS patients and 462 control subjects from two cohorts and found that the common G allele is associated with disease susceptibility (p=0.0015). The UCP2 –866G allele is correlated with lower levels of UCP2 expression as shown here in vitro and in vivo. Thus, UCP2 promoter polymorphism may contribute to MS susceptibility by regulating the level of UCP2 protein in the central nervous and/or the immune systems.S. Vogler and R. Goedde contributed equally to this work     

Association of interleukin-1 receptor antagonist gene polymorphism and susceptibility to human brucellosis

The aim of this study was to determine the influence of the polymorphism within the intron 2 of the interleukin-1 receptor antagonist gene (IL-1Ra) on the susceptibility to or development of brucellosis. A total of 255 patients with brucellosis and 162 healthy volunteers were genotyped for polymorphisms in intron 2 of the IL-1Ra gene. The frequency of allele 2 of the IL-1Ra gene was significantly higher in patients with brucellosis compared with the controls (24.5% vs 18.5%, P = 0.03). Although the heterozygosity was more prevalent in patients than in control individuals, it did not have any statistical significance (P = 0.1). Alleles 3, 4, and 5 were absent in our study population. This work is the first that verifies a significant association between genetic polymorphism of IL-1Ra and susceptibility to brucellosis.     

CCR5-Delta32 genetic polymorphism associated with benign clinical course and magnetic resonance imaging findings in Brazilian patients with multiple sclerosis

The CCR5 chemokine receptor has been implicated in the pathogenesis of multiple sclerosis (MS). This research was carried out to investigate the association between the CCR5-Delta32 deletion in 124 patients with MS from Southern Brazil. Ninety-eight (79.0%) patients presented with relapsing-remitting MS (RR-MS), 17 (13.7%) secondary progressive MS (SP-MS), 8 (6.5%) primary progressive MS (PP-MS) and one (0.8%) clinically isolated syndrome (CIS). The control group consisted of 127 healthy blood donors from the same geographic region. The disease severity was assessed clinically using the Expanded Disability Status Scale (EDSS). Genomic DNA was extracted from peripheral blood cells and the genetic polymorphism was evaluated by polymerase chain reaction. Of the MS patients, 85 (68.5%) were females (p=0.0093). The CCR5-Delta32 frequency among the controls was 5.5%, and did not differ from that observed among the MS patients (4.8%) (p=0.7337). The mean (+/-SD) age at disease onset among the carriers and non-carriers of the CCR5-Delta32 allele was 31.7 (+/-11.1) and 36.6 (+/-12.0) years, respectively (p=0.1312). The duration (+/-SD) of the disease was 11.2 (+/-12.9) and 7.7 (+/- 5.6) years among the CCR5-Delta32 heterozygous, and CCR5 wild type, respectively (p=0.396). The mean (+/-SD) EDSS among the MS patients carriers and non-carriers of the CCR5-Delta32 allele was 2.4+/-1.2 and 2.67+/-2.2, respectively (p=0.9796). The MRI findings in MS patients with the CCR5-Delta32 genotype exhibited lower positive gadolinium enhancing-imaging (p=0.0013) and lower brain atrophy (p=0.1333) than MS patients with the CCR5 wild-type genotype. Despite that the differences were not significant, the results suggested that the disease onset and progression to disability may be prolonged in MS carriers of CCR5-Delta32, and CCR5-Delta32 could be considered a favorable prognostic biomarker of MS. Further studies comprising larger numbers of individuals carrying non-wild-type haplotypes are needed to determine CCR5-Delta32 involvement in the specific process of MS pathology and pathogenesis.