PPARγ2基因Pro12Ala多态性与老年超重和肥胖的相关性

目的探讨PPARγ2基因Pro12Ala多态性与辽宁地区汉族老年人群超重和肥胖的相关性。方法用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术,对186例老年超重肥胖者和186例正常对照人群PPARγ2基因外显子的Pro12Ala多态性基因型进行对照分析。结果 PPARγ2基因12Ala等位基因在老年超重肥胖组和对照组的频率分别为4.3%、2.1%,两者间有显著性差异(P=0.046)。结论 PPARγ2基因外显子的Pro12Ala多态性与老年超重和肥胖相关。     

过氧化物酶体增殖物激活受体γ2基因Pro-12Ala多态性与代谢综合征的相关性研究

目的旨在探讨过氧化物酶体增殖物激活受体γ2（PPARγ2）基因Pro12Ala多态性对β细胞功能储备、胰岛素抵抗作用及与代谢综合征的相关性.方法随机选取湖北地区无亲缘关系的新诊断的2型糖尿病汉族人289例,其中伴高血压病组（HTD）132例,血压正常组（NTD）157例.应用聚合酶链反应-限制性片段长度多态性技术,进行基因突变检测.结果（1）湖北地区汉族人群体中2型糖尿病Ala12携带者（和Ala/Ala基因型）及Ala12等位基因频率分别为0.042;0.015,与正常人群没有差异;本研究中PPARγ2 Pro12Ala与2型糖尿病患者性别、年龄、体重指数、血脂谱无相关性.（2）PPARγ2Pro12Ala多态性与2型糖尿病的高血压呈负相关.（3）在HTD组中PPARγ2Pro12Ala与保护β细胞对葡萄糖刺激胰岛素分泌反应（P＜0.05）、减少胰岛素抵抗有关（P＜0.05）.结论PPARγ2基因是2型糖尿病、高血压病的重要遗传因素,PPARγ2基因负性突变是2型糖尿病和胰岛素抵抗相关疾病的保护因素.     

基于MnSOD9Ala16Val基因多态性的缺血性脑卒中发病风险预测模型的构建研究

目的 探讨MnSOD9Ala16Val基因多态性与缺血性脑卒中(IS)相关性并构建风险预测模型。方法 纳入2018年6月至2019年6月四川省广安市人民医院行健康体检人群,根据是否诊断为IS,分为IS组与非IS组,每组各50例,收集其一般人口学资料、实验室检查指标及MnSOD9Ala16Val基因型等临床资料。采用二元Logistic回归分析环境暴露因素、MnSOD9Ala16Val基因多态性与IS易感性的相关性,并构建回归预测模型,通过ROC曲线对模型进行评价。结果 单因素分析表明,年龄、吸烟、糖尿病、高血压、其他血管疾病、空腹血糖(FBG)及MnSOD9Ala16Val基因多态性,两组间比较差异有统计学意义(χ2=41.558、7.250、5.005、4.006、9.458、5.005、12.148,P 0.05)。二元Logistic回归分析表明,年龄、糖尿病、MnSOD9Ala16Val基因多态性与IS发病风险相关,且VV基因型的IS发病风险为AV或AA基因型的10.666倍[OR(95%CI)=10.666(2.557～44.502),P 0.01]。联合预测因子Y=年龄(≥65岁=1,65岁=0)+0.63×糖尿病(是=1,否=0)+0.65×MnSOD9Ala16Val基因多态性(VV=1,AV或AA=0),ROC曲线下面积(AUC)为0.90,灵敏度为0.80,特异度为0.88,最佳界值为0.83。结论MnSOD9Ala16Val基因型与IS发病风险相关,基于MnSOD9Ala16Val基因多态性的联合预测因子对IS发病风险具有较好的临床诊断价值。     

过氧化物酶体增殖物激活受体γ2基因Pro12Ala多态性与原发性高血压关系的meta分析

目的:探讨过氧化物酶体增殖物激活受体γ2(PPARγ2)基因Pro12Ala多态性与原发性高血压(EH)的关系。方法:全面检索PubMed、Medline、万方数据库、中国知网(CNKI)、维普资讯,收集关于PPARγ2基因Pro12Ala多态性与EH发生关系的病例-对照研究,采用优势比(OR)和95%可信区间(95%CI)评估关联强度,应用RevMan 5.3软件对纳入的研究进行异质性检验和效应值OR合并,漏斗图评估发表性偏倚。结果:共18篇文章被纳入研究,包括20项病例-对照研究,累计HE患者4 492例和对照组人群5 168例。Meta分析结果显示:总体人群PPARγ2基因Pro12Ala各基因型模型及Ala等位基因均与EH相关,根据区域种群不同进一步进行亚组分析,结果显示PPARγ2基因Pro12Ala各基因型模型及Ala等位基因在亚洲人群中与EH有相关性,而在高加索人群中与EH无关。同时,漏斗图未检测出显著的发表性偏倚,且敏感度分析过程显示目前所得的结果是稳定的。结论:PPARγ2基因Pro12Ala多态性在亚洲人群与EH易感性相关,而在高加索人群中与EH无相关性。     

PPARγ基因多态性与冠心病及其危险因素相关性研究概况

过氧化物酶体增殖物激活受体（peroxisome proliferator-activated receptors,PPARs）属于核激素受体家族。PPARs包括3个亚型即α亚型δ亚型和γ亚型,PPARγ2亚型有两个常见多态：C1431T和Pro12Ala。研究证实在人类PPARγ基因多态性与动脉粥样硬化的发生发展密切相关,可导致冠心病的发生发展,并与冠状动脉粥样硬化性心脏病多个危险因素,如2型糖尿病、高血压、肥胖、血脂异常、代谢综合征有关。因此PPARγ基因多态性不仅直接参与了冠心病发生发展的多个环节,并可通过增加冠心病的危险因素来进一步促进冠心病的发生与发展。临床通过测定PPARγ基因多态性有可能分析出发生2型糖尿病、高血压、代谢综合征、血脂异常、肥胖和冠心病发病的可能性和风险,发现与诊断冠心病的高危人群。     

肿瘤坏死因子-α基因多态性与非酒精性脂肪性肝病的关系

目的研究肿瘤坏死因子-α(TNF-α)基因-308位点及-238位点多态性在非酒精性脂肪性肝病(NAFLD)患者中的分布,及其在胰岛素抵抗(IR)和 NAFLD 发病中的地位。方法运用聚合酶链反应-限制性片段长度多态性检测117例 NAFLD 患者 TNF-α基因—308位点及—238位点多态性,其中伴肥胖者60例,非肥胖者57例,同时测定患者空腹血清胰岛素(FINS)及空腹血糖,通过体内平衡代谢指数(HOMA)评估 IR,并与120名健康者对照。结果 NAFLD 患者与正常对照组 TNF-α基因-238位点基因多态性分布差异有统计学意义(29.9%比15.8%,P<0.05),而—308位点差异无统计学意义(P>0.05)。NAFLD 患者血清 HOMA-IR、TNF-α明显高于对照者[2.50±0.68比1.16±0.68,(10.54±3.19)ng/L 比(4.54±3.10)ng/L,P<0.01]。FINS、HOMA-IR 在 TNF-α基因-238位点基因变异组明显高于正常基因型组(P<0.05),但在—308位点变异组差异无统计学意义(P>0.05)。NAFLD 患者中无论肥胖或非肥胖患者均较正常对照人群在 TNF-α基因-238位点多态性分布及HOMA-IR、TNF-α差异有统计学意义(P<0.05)。肥胖及非肥胖的 NAFLD 患者之间 HOMA-IR、TNF-α差异无统计学意义(P>0.05)。结论 NAFLD 患者 IR 与其体重关系不显著,非肥胖 NAFLD患者同样有 IR 发生。TNFα基因-238位点 G/A 变异与 IR、NAFLD 易感性相关,TNFα基因-308位点 G/A 的突变与 IR 易感性不相关。NAFLD 发病与 IR、TNF-α密切相关。     

PPAR-γ基因Pro12Ala多态性与非酒精性脂肪性肝病易感性的Meta分析

目的探讨PPAR-γ基因Pro12Ala多态性与非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)易感性的关系。方法检索Pub Med、Web of Science、万方数据库、中国知网(CNKI)、维普数据库,检索时间为建库至2014年8月30日,收集关于PPAR-γ基因Pro12Ala多态性与NAFLD易感性的病例-对照研究,采用Rev Man 5.2和Stata 12.0软件进行Meta分析。结果最终纳入8个病例-对照研究,包括1 697例病例和2 427名对照。其中5篇研究涉及亚洲人群,3篇涉及白种人群。Meta分析结果显示:PPAR-γ基因Pro12Ala多态性的基因型分布在病例组与对照组中差异无统计学意义(P0.05),基于种族的亚组分析也得到相同结果。结论 PPAR-γ基因Pro12Ala多态性与NAFLD的易感性无明显相关性。     

老年慢性心力衰竭病人锰超氧化物歧化酶Ala-9Val基因多态性与预后的相关性研究

目的探讨陕西地区汉族人群中,锰超氧化物歧化酶(Mn-SOD) Ala-9Val基因多态性与老年慢性心力衰竭(CHF)病人预后的关系。方法选择2015年1月至2017年6月于我科住院治疗的老年CHF病人280例纳入CHF组,另随机选择同期在我院体检的健康志愿者100例为对照组。采用PCR-限制性片段长度多态性法检测Mn-SOD Ala-9Val基因多态性,比较2组Mn-SOD Ala-9Val基因多态性差异。将CHF组病人分为Val/Val亚组和(Ala/Ala+Ala/Val)亚组,统计比较2个亚组随访3年内心源性死亡发生率,再根据随访3年内是否发生心源性死亡进一步分为死亡亚组与存活亚组,统计分析CHF病人3年内心源性死亡的危险因素。结果 2组Mn-SOD基因Ala-9Val位点基因型和等位基因分布频率差异均无统计学意义(P均0.05)。Val/Val亚组和Ala/Val+Ala/Ala亚组3年死亡率分别为31.86%和15.69%,差异具有统计学意义(P=0.003)。多因素Logistic回归分析结果显示,携带Val/Val基因型是老年CHF病人3年内心源性死亡的独立危险因素(OR=1.759,95%CI:1.151～2.687,P=0.003)。结论陕西地区汉族人群中,Mn-SOD Ala-9Val基因多态性与老年CHF病人预后相关。     

罗格列酮与非酒精性脂肪性肝病

脂肪性肝病(FLD)是遗传-环境-代谢应激相关因素所致的以肝细胞脂肪变性为主的临床病理综合征.FLD包括酒精性肝病(ALD)和非酒精性脂肪性肝病(NAFLD).随着社会经济的发展,生活水平的提高,NAFLD已成为健康体格检查肝功能异常的主要原因.     

非酒精性脂肪性肝病基因多态性的巢式病例-对照研究

目的 探讨广东省汉族人中代谢综合征(MS)相关基因多态性和非酒精性脂肪性肝病(NAFLD)发病易感性的关系.方法 在广东省流行病学调查中抽取符合中华医学会肝病学分会诊断标准.且B超、临床和实验室检查结果为典型的成年NAFLD患者50～117例,采用巢式病例-对照方法,现场按1 : 1匹配,选择非NAFLD人群作对照.各受试者均由静脉血中提取DNA,采用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)法检测7个候选基因9个位点单核苷酸多态性(SNP).结果 基因SNP和NAFLD的发病易感性相关.正相关的因子(即增加易感性)为:肿瘤坏死因子-α(TNF-α)-238、脂联素-45、瘦素-2548、过氧化物酶体增殖物激活受体-γ-161、磷脂酰乙醇胺N-甲基转移酶-175.负相关的因子(即降低易感性)为:脂联素-276、肝脂肪酶-514.不相关的因子为:TNF-α-380、PPAR共激活因子-1α-482.结论 多数MS相关的细胞因子基因SNP和NAFLD发病易感性相关.     

Functional activity of the triplicated alpha alpha alpha 4.2/gene rearrangement

Function of the triplicated alpha alpha alpha 4.2/gene rearrangement was assessed by measurement of Hb Bart's and hematological phenotype including alpha/beta biosynthesis ratio. Increased output of alpha globin chains in alpha alpha alpha 4.2/-- compared to alpha alpha/-- was found in a cord blood. In contrast, hematological phenotypes in two family members with the alpha alpha alpha 4.2/-- genotype were consistent with that expected in alpha alpha/--. This would suggest that the additional alpha gene in the alpha alpha alpha 4.2/rearrangement has variable expression.     

1 Alpha 2 alpha 3 alpha collagen is arthritogenic.

Native 1 alpha 2 alpha 3 alpha collagen (500 micrograms per rat) was both immunogenic and arthritogenic in Alderley Park rats (46% developed arthritis) but only immunogenic in Sprague-Dawley rats. Conversely, native type II collagen (500 micrograms per rat) was immunogenic and arthritogenic in both strains (64% arthritic in Alderley Park strain, 57% arthritic in Sprague-Dawley strain). The inflammatory polyarthritis induced by 1 alpha 2 alpha 3 alpha collagen was similar to that produced by native type II collagen in clinical appearance, time of onset, and histology. Antibodies raised to native bovine type II collagen cross-reacted with native 1 alpha 2 alpha 3 alpha collagen and vice versa. Thus the minor collagen component of cartilage, the 1 alpha 2 alpha 3 alpha collagen, as well as the major collagen component, type II collagen, are immunogenic and arthritogenic in the rat, with strain differences.     

The monoclonal antibodies alpha S-HCL 1 (alpha Leu-14) and alpha S-HCL 3 (alpha Leu-M5) allow the diagnosis of hairy cell leukemia

To define cell surface antigens associated with hairy cell leukemia (HCL), and to gain better insight into the origin of this disease, we developed monoclonal antibodies against spleen cells of a patient with this disease. Although none of these antibodies alone proved specific for the leukemic cells, two of them, designated alpha S-HCL 1 (alpha Leu-14) and alpha S-HCL 3 (alpha Leu-M5) were found to be valuable in the diagnosis of HCL when used in combination. alpha S-HCL 1 recognizes an antigen associated with greater than 95% of B cells in the peripheral blood. Biochemical analysis identified this antigen as a single polypeptide chain with a molecular weight of 150,000 daltons (150 kilodaltons). alpha S-HCL 1 expression on hairy cells is markedly increased when compared with normal B lymphocytes isolated from peripheral blood, tonsils, and spleens. alpha S-HCL 3 reacts with an antigen present on hairy cells but also on monocytes, macrophages, in a lower density on neutrophils, and a small percentage (less than 2%) of lymphocytes. The antigen recognized by alpha S-HCL 3 is composed of a non-covalently linked biomolecular complex of 90 and 150 kilodaltons. Since the HCL 3 antigen was not detectable on other lymphomas of either T or B cell type, the co-expression of S-HCL 1 and S-HCL 3 on hairy cells is a unique marker for this disease.     

Protein kinase C alpha modulates liver X receptor alpha transactivation

Liver X receptor alpha (LXRalpha), an oxysterol-activated nuclear hormone receptor, regulates the expression of genes involved in lipid and cholesterol homeostasis and inflammation. We show here that transactivation by LXRalpha in monkey kidney COS-1 (Cos-1) cells is decreased by activation of the protein kinase C (PKC) signaling pathway. In transient co-transfection assays, phorbol myristate acetate (PMA) suppressed LXR-dependent transactivation of LXR-responsive reporter genes or the natural promoter of the human ATP-binding cassette (ABC), ABCA1 gene. The decrease in LXR transactivation after PMA treatment was also observed in human embryonic kidney (HEK) 293 and human hepatocellular carcinoma (HepG2) cells. Moreover, endogenous LXR target genes, ABCA1 and sterol response element-binding protein-1c, were also decreased by PMA treatment in HEK293 cells as assessed by real-time PCR. The PMA-mediated decrease of LXR activity was blocked by the PKC inhibitor bisindolylmaleimide and mimicked by constitutively active PKCalpha. Nuclear extracts treated with PMA show no decrease in LXRalpha DNA binding as assessed by mobility shift and chromatin immunoprecipitation assays. Additionally, in vitro kinase assays demonstrate that PKCalpha can phosphorylate LXRalpha. Our findings reveal a mode of regulation of LXRalpha that may be relevant to disease conditions where aberrant PKC signaling is observed, such as diabetes.     

A novel mutation of the alpha2-globin causing alpha(+)-thalassemia: Hb Plasencia [alpha125(H8)Leu--Arg (alpha2)

We describe, in a Spanish family with moderate microcytosis and hypochromia, a novel nondeletional alpha-thalassemia (thal) mutation localized on the alpha2-globin gene. DNA sequencing revealed a point mutation at codon 125 (CTG --> CGG) in the heterozygous state, that was confirmed by restriction analysis. The resulting variant, which causes a nondeletional alpha-thal, was named Hb Plasencia [alpha125(H8)Leu --> Arg (alpha2)] after the place of residence of the affected family.