儿童EBV感染与IL-10启动子基因多态性的相关性

目的探讨白细胞介素-10(Interleukin-10,IL-10)启动子基因-1082A/G、-819T/C、-592A/C位点多态性与儿童EB病毒(Epstein-Barr virus, EBV)感染易感性及肝功能损害相关性。方法选取杭州师范大学附属医院儿科2019年1月-2019年12月收治EBV感染所致传染性单核细胞增多症(Infectious mononucleosis, IM)患儿87例纳入感染组,其中肝功能损害52例(肝损组),无肝功能损害35例(无肝损组),并选取同期未感染EBV的健康儿童78名为对照组。应用Sanger双脱氧链终止法检测IL-10启动子基因-1082A/G、-819T/C、-592A/C位点的基因多态性。结果 IL-10-1082A/G、IL-10-819T/C、IL-10-592A/C位点在感染组与对照组之间基因型及等位基因比较差异无统计学意义;IL-10-1082A/G基因型与等位基因在肝损组及无肝损组之间无统计学差异,IL-10-819T/C的CC基因型频率与IL-10-592A/C的CC基因型频率在肝损组中更高(P0.05),但两者的等位基因在肝损组及无肝损组中无明显统计学差异;IL-10-819T/C与IL-10-592A/C两个位点基因高度连锁。结论 IL-10启动子基因-1082A/G、-819T/C、-592A/C位点多态性与杭州地区儿童EBV易感性无关,IL-10-819T/C位点及IL-10-592A/C位点的CC基因型可能是IM患儿肝功能损害的影响因素之一,但需要更多检验。-819T/C基因型与-592A/C基因型高度连锁。     

白细胞介素10基因-592 C/A和-819 C/T多态性与β-内酰胺类抗菌药物过敏的相关性研究

目的探讨白介素10（IL-10）基因启动子-592C／A和-819C／T基因多态性，在哥内酰胺类抗菌药物过敏汉族患者与正常人群中的分布及与药物过敏的相关性。方法应用聚合酶联反应-限制性片段长度多态性技术（PCR-RFLP），对44例争内酰胺类抗菌药物过敏的汉族患者及44例对照人群，IL-10基因-592C／A和-819C／T位点进行研究，探讨两者之间的关系，并通过对PCR产物测序，验证聚合酶链反应-限制性片段长度多态性技术的特异性。结果女性药物过敏患者与对照组间的单核苷酸多态性（SNP）差异有统计学意义（P〈0．05，OR=17．5，CI：1.26～533．07），男性药物过敏患者与对照组间差异无统计学意义。结论白介素10基因-592C／A和～819C／T位点多态性可能是中国汉族女性争内酰胺类抗菌药物药物过敏的易感性标志。     

四川凉山彝族成人FTO基因多态性与肥胖的关联研究

  目的  了解四川凉山彝族成人脂肪和肥胖相关基因（fat mass and obesity associated gene,FTO）多态性与肥胖的关联。  方法  采用病例对照研究方法,病例组为彝族移民流行病学调查中收集的肥胖者[体重指数（body mass index,BMI）≥28 kg/m2],共322例;对照组为非肥胖非超重者（BMI < 24 kg/m2）,按年龄和性别与病例组进行1:2频数匹配,共644例。采用TaqMan实时荧光定量聚合酶链式反应（polymerase chain reaction,PCR）法对FTO基因（rs1121980和rs17817449）进行基因分型。采用非条件Logistic回归分析模型分析两位点多态性与肥胖的关联。  结果  彝族农民中,加性模型和显性模型下,rs1121980位点与肥胖均存在统计学关联（加性模型:OR=1.45,95% CI:1.01~2.07,P=0.042;显性模型:OR=1.52,95% CI:1.01~2.31,P=0.048）。彝族农民中未见rs17817449与肥胖存在统计学关联（均有P>0.05）。彝族移民中,两位点（rs1121980和rs17817449）与肥胖均未见统计学关联（均有P>0.05）。  结论  彝族农民FTO rs1121980多态性与成人肥胖存在统计学关联,A等位基因是肥胖的危险因素。彝族移民FTO两位点与成人肥胖均未见关联。     

成纤维细胞生长因子受体2（FGFR2）多态性与乳腺癌易感性的关联研究

目的探讨中国女性人群成纤维细胞生长因子受体2（Fibroblast growth factor receptors2,FGFR2）rs2981582C/T、rs2420946C/T以及rs1219648A/G多态性与乳腺癌易感性的关系。方法采用病例-对照研究,以引物介导的限制性多聚酶链反应（PIRA-PCR）和多聚酶链反应-限制性片段长度多态性（PCR-RFLP）方法对673例乳腺癌病例和787例正常对照进行FGFR2基因型检测,采用多元Logistic回归分析基因型与乳腺癌易感性之间的关系。结果 FGFR2三个多态位点的基因型频率分布在病例组和对照组间差异均有统计学意义（P值分别为0.002,0.034和0.002）,其中经调整年龄、月经初潮年龄、绝经状况、哺乳史、生育史、口服避孕药及肿瘤家族史后,rs2420946和rs1219648两位点的变异基因型可增加乳腺癌的发病风险;rs2981582变异基因型也可以增加乳腺癌的发病风险。分层分析结果显示,在绝经前、有哺乳喂养史以及有生育史女性中,3个多态性位点改变对乳腺癌易感性的影响更为显著。结论 FGFR2遗传多态性rs2981582C/T、rs2420946C/T以及rs1219648A/G可增加中国女性罹患乳腺癌的危险性,预期可以作为乳腺癌易感性的重要生物标志物。     

IL-10基因启动子多态性与强迫症关系

目的 探讨白细胞介素-10（IL-10）基因启动子多态性与强迫症（OCD）的关系。方法 381例OCD患者和485名健康对照为研究对象,通过聚合酶链式反应与限制性片段长度多态性（PCR-RFLP）基因分型技术对IL-10基因标签单核酸多态性（SNP）位点592A/C（rs1800872）、1082A/G（rs1800896）、819T/C（rs1800871）进行基因分型;以耶鲁-布朗强迫量表（Y-BOCS）评定OCD患者的病情。结果 OCD组和对照组IL-10基因rs1800872、rs1800896、rs1800871位点在基因型频率分布与等位基因频率分布差异均无统计学意义（P>0.05）;不同发病年龄女性3个SNPs OCD组与对照组人群基因型与等位基因频率分布无明显差异（P>0.05）;男性rs1800896基因型（χ²=6.51,P=0.039）和等位基因（χ²=6.59,P=0.01,OR=1.84,95%CI=1.15~2.95）频率分布在OCD组与对照组之间存在差异;OCD组男女性别之间rs1800896基因型（χ²=8.08,P=0.02）和等位基因（χ²=6.97,P=0.008,OR=1.95,95%CI=1.18~3.23）频率分布也存在差异。结论 IL-10基因（rs1800896）可能与男性OCD易感性有关。     

白细胞介素10基因多态性与子宫内膜异位症易感性的关系研究

目的 分析子宫内膜异位症(endometriosis,EMs)患者白细胞介素10(interleukin-10,IL-10)的启动子区域转录起始位点上游第1082位点G→A、819位点C→T及592位点C→A多态性,探讨其与EMs易感性之间的关系.方法 应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)检测EMs组214例和正常对照组160名健康人的启动子区域转录起始位点上游的第1082位点G→A、819位点C→T及592位点C→A碱基转换,采用SPSS11.0软件包统计分析各位点的基因型分布和等位基因频率.结果 IL-10-1082位点的多态性在EMs组(AA:87.90%;GA:12.10%)与对照组(AA:87.50%;GA:12.50%)的基因频率差异无统计学意义(x2=0.01,P=0.919).EMs组和对照组的IL-10-819 TT、CT、CC型基因频率均依次等同于IL-10-592的AA、CA、CC基因型.IL-10-819和-592基因型在EMs组分布(TT或AA:41.12%;CT或CA:47.66%;CC:11.21%)与对照组(TT或AA:53.75%;CT或CA:37.50%、CC:8.75%)差异无统计学意义(x2=5.87,P=0.053).但患者组IL-10-819的CT及-592的CA基因型频率较对照组增高,差异有统计学意义(校正后OR=1.88,95%CI=1.10～3.21,x2=5.24,P=0.021),-819和-592位点的C等位基因与EMs发病风险具有显著相关性(OR=1.42,95%CI=1.04～1.95,x2=4.81,P=0.028).EMs组IL-10-819(-592)位点的CC(CC)、CT(CA)基因型患者的血清中IL-10水平较TT(AA)基因型高[CA/CT:(50.12±82.40)pg/ml,CC(91.00±118.23)pg/ml,TT/AA(21.45±22.10)pg/ml],差异有统计学意义(F=2.492,P=0.048;F=1.852,P=0.008).结论 IL-10-592C及-819C等位基因与IL-10高表达相关,并与EMs的易感性具相关性,也与EMs的发病风险相关.     

雌激素受体α基因多态性与膀胱癌发病风险的相关性

  目的  研究雌激素受体α基因单核苷酸多态性与膀胱癌易感性的关系。  方法  从两医院收集膀胱癌新发病例220例及同期健康体检对照220例,通过问卷收集研究对象一般情况,查阅电子病历收集临床检查资料;用多重高温连接酶检测反应技术（improved multiple ligase detection reaction,iMLDR）检测基因型;采用酶联免疫法检测两组血清中雌激素受体α（estrogen receptor alpha,ESRα）的表达量。  结果  病例组的体重指数、饮食及生活行为习惯和血红蛋白、中性粒细胞百分率等临床检查结果与对照组人群差异均有统计学意义（均有P < 0.05）。rs1801132位点基因及基因型频率与病理分级（χ2=9.607,P=0.022;χ2=24.468,P < 0.001）、远处转移（χ2=2.367,P=0.027;χ2=21.758,P=0.001）有关。膀胱癌患者血清中ESRα受体表达量低于正常人群（t=5.588,P < 0.001）。rs1801132位点多态性在不同基因型人群中膀胱癌发病风险均有统计学差异[GG:OR（95% CI）=0.325（0.141~0.751）,P=0.009;GC:OR（95% CI）=0.409（0.198~0.847）,P=0.016]。  结论  rs1801132位点多态性与膀胱癌发病相关,GG/GC基因型在膀胱癌中具有保护作用;rs2234693位点多态性与膀胱癌无相关性。     

ABCA3基因多态性与新生儿呼吸窘迫综合征易感性关系研究

目的：探讨ATP结合盒转运蛋白A3基因（ABCA3） rs13332514（C．1059G/A）、rs117515055（C．213C/T）两个多态性位点与陕西汉族人群新生儿呼吸窘迫综合征（ NRDS）的遗传易感性。方法用SNaPshot多重微测序技术检测60例陕西汉族NRDS患者和120名健康对照者 ABCA3基因 rs13332514（ C．1059G/A ）、rs117515055（ C．213C/T ）两个多态性位点。结果rs117515055位点有两种基因型,对其进行比较,发现T等位基因在病例组（5．1％）高于对照组（3．1％）,但是差异无统计学意义;rs13332514位点CC基因型频率及C等位基因频率在病例组高于对照组（50．8％vs44．1％,69．5％vs63．5％）,差异亦无统计学意义。结论 rs117515055位点的T等位基因及rs13332514位点的C等位基因可能与汉族人群的NRDS有关,还需扩大样本量做进一步研究。     

IFITM3基因rs12252位点多态性与中国人群流感易感性:基于研究的序贯Meta分析

  目的  系统评价干扰素诱导跨膜蛋白3（interferon-induced transmembrane protein 3,IFITM3）基因rs12252位点多态性与中国人群流感易感性的定量关系。  方法  检索Medline、PubMed、Embase、Web of Science以及中国知网、万方、维普数据库,收集IFITM3与中国人群流感易感性相关的文章。采用Meta分析方法对收集的文章进行定量地综合分析。  结果  本次研究共纳入7篇文献,共计919例流感感染的病例,涉及到甲型流感（H7N9、H1N1pmd09、H3N2）及乙型流感病毒,序贯Meta分析显示本研究纳入的研究总样本已达到了得到稳定阳性结局所需的样本量。Meta分析结果发现,IFITM3基因的rs12252多态性与中国人群流感病毒易感性存在关联,携带rs12252 C等位基因的人群更易发生流感（C vs T:OR=1.67,95% CI:1.45~1.92;CC vs TT:OR=2.61,95% CI:1.97~3.46;TC vs TT:OR=1.55,95% CI:1.20~2.00;CC vs TC+TT:OR=2.01,95% CI:1.49~2.72;CC+TC vs TT:OR=8.90,95% CI:4.94~16.06）。  结论  IFITM3基因rs12252位点多态性是中国人群发生流感的危险因素。     

CASP3和CASP7基因多态性与噪声性听力损失易感性关系

目的 探讨细胞凋亡通路相关基因CASP3和CASP7多态性与中国汉族人群噪声性听力损失（NIHL）易感性之间的关联。方法 研究对象来自2014年杭州市1 549名噪声接触工人听力损失的横断面调查,采用1：1配对病例对照研究,病例组为电测听双耳高频平均听阈>25 dB（A）的工人,对照组为性别、年龄、接噪工龄、工作岗位与病例匹配且双耳所有频段听阈均≤25 dB（A）的工人,共272对。PCR-LDR法检测2个SNP位点的基因型。采用多因素条件logistic回归模型分析SNP位点与NIHL的关联,并以叉生分析计算基因-环境交互作用。结果 χ²检验分析发现,CASP3基因rs1049216等位基因（C、T）频率组间分布有统计学差异（OR=0.68,95%CI=0.50~0.93）,而基因型频率组间差异无统计学意义（P>0.05）;CASP7基因rs10787498等位基因及基因型频率组间分布均无统计学意义（P>0.05）;多因素条件logistic回归显示,CASP3基因rs1049216中,与野生基因型CC相比,突变基因型（CT+TT）为NIHL的保护因素（调整OR=0.65,95%CI=0.43~0.97）;叉生分析表明rs1049216位点与文化程度、睡眠时间存在交互作用（P≤0.001）,NIHL的危险性降低（OR值变小）。结论 CASP3基因rs1049216位点可能与中国汉族人群NIHL易感性有关,且可能与文化程度、睡眠时间存在交互作用。     

广西地区人群IL-6及IL-10单核苷酸多态性与HBV相关肝癌关联研究

目的 探讨广西地区人群IL-6和IL-10基因单核苷酸多态性(SNP)与HBV相关肝癌的关系.方法 采用以医院为基础的病例对照研究方法,以381例肝癌患者为病例组,340例HBsAg携带者及359例健康体检者为对照组.应用荧光定量PCR对IL-6基因-572位点,IL-10基因-819和-592位点进行基因分型.采用非条件logistic回归模型分析比较携带不同基因型人群罹患肝癌的风险.结果 IL-6基因-572位点G/C等位基因在病例组、HBsAg携带组及健康对照组中分布差异有统计学意义(P＜0.05),与CC基因型相比,携带GG基因型个体慢性HBV感染危险性增加(OR=2.171,95%CI:1.068-4.415).IL-10基因-819位点T/C等位基因在三组的分布差异有统计学意义(P＜0.05),与CC基因型相比,携带TT基因型健康个体罹患肝癌的危险性增加(OR=2.791,95%CI:1.326～5.874).携带TT基因型的HBsAg携带者罹患肝癌的风险也增加(OR=3.522,95%CI:1.707～7.266).IL-10基因-592位点A/C等位基因在三组中的分布差异无统计学意义(P＞0.05),与CC基因型相比,携带AA基因型健康个体罹患肝癌的危险性降低(OR=0.389,95%CI:0.173-0.875),携带AA基因型的HBsAg携带者肝癌的罹患风险也降低(OR=0.336,95%CI:0.154-0.734).结论 IL-6基因-572位点SNP与广西地区人群慢性HBV感染有关,IL-10基因-819位点TT基因型个体罹患肝癌的风险增加,IL-592位点从基因型个体罹患肝癌的风险降低.

Abstract：

Objective To investigate the association between single nucleotide polymorphisms (SNPs)in cytokine IL-6, IL- 10 genes and HBV-related hepatocellular carcinoma(HCC). Methods A hospital-based case-control study was conducted in 381 cases with HBV-related HCC, 340 HBsAg carriers and 359 non-tumor controls. Genotypes of-572 site of IL-6 gene and-819, -592 sites of IL-10 gene were determined by real-time polymorphism chain reaction. Unconditional logistic regression was used to estimate the odds ratios(ORs)and 95 confidence intervals(C/s). Results For the G/C alleles of -572 loci on IL-6 gene, there were significant differences between the three groups(P＜0.05). Compared with CC genotype, GG genotype increased the risk of HBV infection (OR=2.171,95% Ch 1.068-4.415), but did not seem to be associated with HCC. For the alleles of-819 and -592 site of IL-10 gene, there were significant differences between the three groups(P＜0.05). Compared with CC genotype, TT genotype increased the risks of both HCC(OR=2.791,95%CI:1.326-5.874), and HCC in HBsAg carriers(0R=3.522,95%CI: 1.707-7.266). When compared with CC genotype on -592 site, the AA genotype reduced the risk of both HCC(OR=0.389, 95% CI:0.173-0.875), and HCC in HBsAg carriers(OR=0.336, 95% CI: 0.154-0.734). Conclusion The SNPs in -572 site of IL-6 gone might be associated with the risk of HBV infection. The SNPs in -819 site of IL-10 gene increased the risk of HCC, but -592 site of IL-10 gene decreased the risk of HCC.     

Influence of IL10 gene polymorphisms on the severity of liver fibrosis and susceptibility to liver cirrhosis in HBV/HCV-infected patients

BackgroundPrevious studies about the association of the interleukin-10 (IL-10) polymorphisms with the progression of liver fibrosis or cirrhosis susceptibility in chronic hepatitis B/C (CHB/C) disease were inconsistent. The aim of this meta-analysis was to derive a more precise estimation of the association.MethodsWe searched Medline, PubMed, EMBASE and Web of Science electronic databases using the following key words: liver fibrosis/cirrhosis, IL10, and polymorphism. Statistical analyses were performed by STATA11.0 software, with odds ratios (ORs) and their 95% confidence intervals (CIs).Results12 independent studies in relation to IL10-1082A/G, -819C/T and -592C/A polymorphisms were included in our study, which consisted of 197 moderate/severe liver fibrosis cases and 426 mild fibrosis controls as well as 536 liver cirrhosis cases and 881 non-cirrhosis controls. The results indicated that a significantly decreased risk of moderate/severe fibrosis was associated with the GCC haplotype (IL10-1082G, -819C and -592C) in the overall CHB/C patients (OR: 0.547, 95% CI: 0.317–0.946, P = 0.031). We did not detect any significant association between these polymorphisms and liver cirrhosis susceptibility in the total population or a subgroup of Asians. However, subgroup analyses by different aetiologies showed that the -819T heterozygotes (TC) were associated with a significantly increased risk of HCV-related liver cirrhosis in the Japanese population (OR: 1.254, 95% CI: 1.033–1.522, P = 0.022).ConclusionsThe putative high IL-10 production haplotype GCC is more likely to be associated with less severe liver fibrosis in CHB/C patients. Additionally, the IL10-819T allele may be a susceptible factor for HCV-related liver cirrhosis in the Japanese population.     

Identification of Functional Genetic Polymorphisms at IL-10 Promoter Region and their Association with Risk of Ischemic Stroke in Chinese Han Population

Background

Pleiotropic cytokine interleukin-10 (IL-10) has been suggested as modifying risk for atherosclerosis. Promoter region genetic polymorphism of IL-10 gene is known to be associated with the level of IL-10 production. Through these effects, they might be involved with the ischemic stroke (IS). Our aim was to assess the nature of the functional polymorphisms in IL-10 promoter and any links with IS in Chinese Han population.

Methods

The IL-10 -1082 G>A, -819 C>T and -592 C>A functional polymorphisms were determined by TaqMan SNP Genotyping assays in 1296 subjects (648 IS patients diagnosed by CTs or/and magnetic resonance imaging (MRI) and 648 normal healthy controls from Chinese Han Population). Multivariate logistic regression analysis was used to show the association between the IL-10 genotypes and the IS events.

Results

We found that the CC genotype of -819 C>T was more common in controls than IS subjects (P<0.05, corrected for multiple testing) in the Han population. CC carriage may be associated with the decreased risk of IS in the Han ethnic group (OR 0.65, 95% CI 0.43-0.97). In addition, the CC genotype in -592 C>A and GG genotype in -1082 G>A are all extremely low in Chinese Han cases and controls.

Conclusions

The G allele frequency at the -1082 promoter region of IL-10 was rare in Chinese Han population which are diffierent from American/European populations.. IL-10 -819 C>T may be an independent protective factor for IS in the Chinese Han population.

     

Lack of association between cytokine gene polymorphisms and silicosis and pulmonary tuberculosis in Chinese iron miners

Silicosis is a fibrotic lung disease produced by the inhalation and deposition of silica dust. The association between silicosis and pulmonary tuberculosis (PTB) has been well established. Cytokines participate in the development and progression of silicosis and PTB. Functional polymorphisms in cytokine genes have been identified that alter cytokine production. The aims of the current investigation were to determine whether functional polymorphisms in the tumor necrosis factor-alpha (TNF-alpha) gene at position -308; in the transforming growth factor-beta 1 (TGF-beta1) gene at positions -509, +869 (codon 10), and +915 (codon 25); in the interleukin-10 (IL-10) gene at position -1,082, -819 and -592; and in the intron 1 of the interferon-gamma (IFN-gamma) gene at position +874 are associated with silicosis and PTB. We conducted a case-control study with 183 silicosis patients and 111 silica-exposed miners, and a 1:2 matched case-control study of 61 PTB cases and 122 PTB-free miners. Genotype analysis was performed on genomic DNA, using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. There was complete linkage disequilibrium (LD) between the -819C and -592C alleles of the IL-10 gene. The genotype frequencies were similar between cases and control subjects for all investigated cytokine polymorphisms (p>0.05). We did not find an association between the different genotypes and severity of silicosis. We assume that these genetic variants do not play a dominant role in silicosis and PTB in our Chinese population.     

Gender-specific effects of cytokine gene polymorphisms on childhood vaccine responses

Cytokine gene polymorphisms affect vaccine responses and gender-specific effects are known for many phenotypes. Therefore, this study investigated gender-specific effects of cytokine gene polymorphisms on vaccine responses. In 263 2-year-old subjects selected for parental history of atopy, boys with IL-4 C-589T and IL-4Ralpha I50V genotypes associated with atopy had increased Diptheria Toxoid (DiphTox) and Tetanus Toxoid (TetTox) responses compared with the remaining alleles (IL-4 C-589T: DipTox p=0.01, TetTox p=0.04; IL-4Ralpha.I50V: DipTox p=0.04, TetTox p=0.08). Contrastingly, girls with IL-10 -592C genotypes associated with atopy had lower levels of DiphTox (p=0.03) and TetTox (p=0.02) responses compared with the remaining allele. Additionally, interaction effects were found for IL-4 C-589T (p=0.01) and IL-4Ralpha I50V (p=0.04) polymorphisms. In conclusion, these findings support the interaction of primary genetic and modifying factors on vaccine responses and the importance of atopic genetics to these responses.     

中国汉族人群MHC区域与胃癌易感性的关联

  目的  探讨主要组织相容性复合体(major histocompatibility complex, MHC)区域遗传变异与胃癌易感性的关联。  方法  采用病例对照研究设计,以中国汉族人群MHC参考数据集为参照,利用SNP2HLA v1.0.3软件对MHC区域进行基因型填补;应用Logistic回归分析模型鉴定MHC区域中与胃癌易感性存在关联的遗传变异;基于公共数据库,通过系统功能注释探索MHC区域内的易感基因和功能性遗传变异。  结果  本研究发现,rs2517714为MHC区域与胃癌发生风险独立关联的遗传位点(OR=1.13, P=2.70×10-8);功能注释显示位于HLA-A基因外显子区域的氨基酸多态性位点及单核苷酸多态性(single nucleotide polymorphism, SNP)可能会影响HLA-A蛋白稳定性;同时,非编码区的功能性遗传变异rs9295829可能通过影响所在区域增强子活性,从而远程调控HLA-A基因表达,共同影响易感基因HLA-A的功能。  结论  MHC区域致病性遗传变异通过影响易感基因HLA-A功能,从而影响胃癌易感性。     

子宫内膜异位症患者IL-10基因多态性与血清、腹腔液蛋白水平的相关性研究

目的进一步确定基因多态性是否为子宫内膜异位症(EMs)患者白细胞介素-10(IL-10)蛋白水平改变的原因之一。方法应用扩增阻滞突变系统-聚合酶链反应(ARMS-PCR)结合DNA测序,以及聚合酶链反应-限制性片段长度(PCR-RFLP)多态性分析方法,检测EMs组和对照组IL-10-1082G/A、-819T/C和-592A/C的基因多态性。ELISA法测定血清和腹腔液中IL-10水平。结果 EMs组和对照组均发现3种单倍型GCC、ACC、ATA,6种单倍型组合,其中以ATA/ATA、ACC/ATA和ACC/ACC占多数。对照组仅-1082位点的多态性与血清、腹腔液IL-10水平相关(P0.01)。EMs组-1082(GG或AG型)、-819(CC或TC型)和-592(CC或AC型)均与腹腔液IL-10水平升高相关(P0.05),其中Ⅰ～Ⅱ期EMs患者仅-1082位点与腹腔液IL-10水平相关(P0.01),Ⅲ～Ⅳ期EMs患者-1082、-819和-592位点的基因型均与腹腔液IL-10水平相关(P0.05)。EMs组-1082、-819、-592基因型与血清IL-10水平无相关性(P0.05)。结论Ⅰ～Ⅱ期EMs影响IL-10表达的遗传学机制主要位于-1082位点,但在Ⅲ～Ⅳ期EMs患者中,腹腔局部因素如某些活性因子等除可作用于-1082位点外,可能还可通过作用于-819和-592位点共同调控IL-10水平,但EMs患者血清IL-10水平与其基因多态无相关性,可能与血清IL-10表达受多种机制调控有关。     

中国老年人HDAC9和PPP3CA基因多态性与衰弱的关联

  目的  探讨组蛋白去乙酰化酶9(histone deacetylase 9, HDAC9) rs2074633及钙调神经磷酸酶催化亚基A(calcineurin catalytic subunit A, PPP3CA) rs17030795的多态性与中国老年人衰弱发生的关联。  方法  本研究纳入衰弱组665例,对照组3 388例。基于基因型频率及五种遗传模型(共显性、加性、显性、隐性和超显性),评估rs2074633及rs17030795多态性与衰弱之间的关联。  结果  在共显性模型中,与携带rs2074633 TT基因型相比,携带TC型(OR=1.99,95% CI: 1.36~2.90)、CC型(OR=2.15,95% CI: 1.48~3.13)的个体发生衰弱的风险增加;在加性(OR=1.28,95% CI: 1.11~1.47)、显性(OR=2.07,95% CI: 1.44~2.98)及隐形模型(OR=1.21,95% CI: 1.01~1.45)中rs2074633多态性均增加衰弱的发生风险;在共显性模型中,与携带rs17030795 AA基因型相比,携带AG(OR=1.72,95% CI: 1.19~2.51)、GG(OR=1.98,95% CI: 1.37~2.87)型的个体发生衰弱的风险增加;在加性(OR=1.28,95% CI: 1.11~1.48)、显性(OR=1.85,95% CI: 1.29~2.66)及隐性(OR=1.25,95% CI: 1.04~1.50)中rs17030795多态性均增加衰弱的发生风险。   结论  HDAC9 rs2074633及PPP3CA rs17030795多态性与中国老年人衰弱发生风险有关。