湖南汉族人群CX3CR1基因多态性分布

目的探讨趋化因子受体CX3CR1基因多态性在湖南汉族健康人群中的分布及其与国内外不同种族之间的差异。方法采用PCR-RFLP技术对150名湖南汉族健康体检者进行CX3CR1基因多态性检测,计算其基因型和等位基因频率,并与国内外多个民族CX3CR1基因多态性分布进行比较。结果湖南汉族人群V249I基因位点有VV和VI两种基因型,以VV基因型为主,没有II基因型,其中VV基因型频率为88%,VI基因型频率为12%,V和I等位基因频率分别为94%和6%;T280M基因位点有TT和TM两种基因型,以TT基因型为主,没有II基因型,其中TT基因型频率分别为95.3%,TM基因型频率为4.7%,T和M等位基因频率分别为97.7%和2.3%。结论湖南汉族CX3CR1基因V249I以VV基因型为主,缺少II和MM基因型,湖南汉族、新疆汉族、景族和傣族都缺少II基因型,T280M以TT基因型为主,缺少MM基因型,湖南汉族CX3CR1基因多态性分布与维吾尔族人群和欧美人群存在较大差异,与国内景族、傣族、新疆汉族和日本人群相似。     

CX3CR1基因多态性与冠心病关联的荟萃分析

目的 探讨CX3CR1-V249I、T280M与冠心病(CAD)的关联性.方法 检索中英文数据库,以得到CX3CR1-V249I、T280M与CAD易感性关系的病例对照研究,采用Meta分析方法 合并V249I、T280M与CAD关联的OR值,同时进行文献发表偏倚检验.结果 共纳入文献6篇.对于V249I,共纳入病例1 551人,对照1 804人,I型相对于V型合并OR=0.85(95%CI=0.67～1.08,P＞0.05);对于T280M,共纳入病例1 555人,对照1 801人,M型相对于T型合并OR=0.82(95%CI=0.70～0.96,P＜0.05).结论 T280M为CAD的保护性因素,V249I与CAD的发生无关联.

Abstract：

Objective To find whether CX3CR1 V249I and T280M are associated with CAD. Methods Database in English and Chinese, including PUBMED, EMbase, were searched to get the case-control studies on the associa-tion between V249I, T280M and CAD. Results Six studies were reviewed. The pooled OR of V249I compared to wild type allele was OR =0. 85(95% CI =0. 67 ～ 1. 08,P >0. 05). The pooled OR of T280M compared to wild type allele was OR =0. 82(95% CI =0. 70 ～ 0. 96, P < 0. 05). Conclusion The T280M is a protective factor of CAD, while the V249I is not associated with CAD.     

湖南汉族人群CX3CRl基因多态性分布

目的 探讨趋化因子受体CX3CR1基因多态性在湖南汉族健康人群中的分布及其与国内外不同种族之间的差异.方法 采用PCR-RFLP技术对150名湖南汉族健康体检者进行CX3CR1基因多态性检测,计算其基因型和等位基因频率,并与国内外多个民族CX3CR1基因多态性分布进行比较.结果 湖南汉族人群V249I基因位点有VV和Ⅵ两种基因型,以VV基因型为主,没有II基因型,其中VV基因型频率为88%,VI基因型频率为12%,V和I等位基因频率分别为94%和6%;T280M基因位点有TT和TM两种基因型,以TT基因型为主,没有Ⅱ基因型,其中TT基因型频率分别为95.3%,TM基因型频率为4.7%,T和M等位基因频率分别为97.7%和2.3%.结论 湖南汉族CX3CRl基因V249I以VV基因型为主,缺少Ⅱ和MM基因型,湖南汉族、新疆汉族、景族和傣族都缺少Ⅱ基因型,T280M以TT基因型为主,缺少MM基因型,湖南汉族CX3CR1基因多态性分布与维吾尔族人群和欧美人群存在较大差异,与国内景族、傣族、新疆汉族和日本人群相似.     

CX3CR1基因多态性与冠心病关联的Meta分析

目的 探讨CX3CR1-V249I、T280M与冠心病（CAD）的关联性。 方法 检索中英文数据库，以得到CX3CR1-V249I、T280M与CAD易感性关系的病例对照研究，采用Meta分析方法合并V249I、T280M与CAD关联的OR值，同时进行文献发表偏倚检验。结果 共纳入文献6篇。对于V249I，共纳入病例1551人，对照1804人，I型相对于V型合并OR=0.85（95%CI=0.67~1.08，P>0.05）；对于T280M，共纳入病例1555人，对照1801人，M型相对于T型合并OR=0.82（95%CI=0.70~0.96，P<0.05）。结论 T280M为CAD的保护性因素，V249I与CAD的发生无关联。     

载脂蛋白E基因多态性在云南省德宏州傣族人群的分布

目的　探讨云南省德宏州傣族人群和昆明汉族人群载脂蛋白E(apolipoprotein E,apo E)基因多态性分布情况。方法　收集171名德宏傣族和71名昆明汉族人群基因组,通过聚合酶链反应-限制性片段长度多态性方法检测apo E基因第4外显子第112位和15 8位的多态性。结果　傣族组apo Eε2 / 2、ε2 /3、ε2 / 4、ε3/ 3、ε3/ 4、ε4 / 4基因型频率依次为:0 .0 0 6、0 .111、0 .0 0 6、0 .789、0 .0 88、0 .0 0 0 ;汉族组依次为:0 .0 0 0、0 .16 9、0 .0 14、0 .718、0 .0 99、0 .0 0 0。apo Eε2、ε3、ε4等位基因频率在傣汉两民族中依次为:0 .0 6 4、0 .889、0 .0 4 7;0 .0 92码、0 .85 2、0 .0 5 6 (P>0 .0 5 )。结论　apo E基因型频率和等位基因频率均存在着民族、种族差异。与国内其它少数民族比较,德宏傣族人群apo Eε2等位基因频率显著低于壮族(P<0 .0 1) ;ε3等位基因频率显著高于朝鲜族、回族、蒙古族、壮族(P<0 .0 5 ) ,极显著高于维吾尔族(P<0 .0 1) ;ε4等位基因显著低于鄂伦春族(P<0 .0 5 ) ,极显著低于维吾尔族、鄂温克族(P<0 .0 1)。与不同种族人群比较,德宏傣族人群apo E基因多态性分布与日本人接近(P>0 .0 5 ) ,而与新加坡、欧美国家人群有较大的差异性。     

云南哈尼族人群HIV感染相关基因多态性研究

目的探讨云南哈尼族人群与人类免疫缺陷病毒（HIV）感染相关的SDFI-31A、CCR2-64I、CX3CRl基因多态性分布。方法通过MassARRAY检测技术分析了78例云南哈尼族人群SDFl-YA、CCR2-64I、CX3CRI单核苷酸多态性,通过与国内外研究结果比较,探讨其特点。结果在SDFl-31A位点上明显高于美国黑人;在CCR2-64I位点上明显高于汉族、黎族、仫佬族、美国黑人和高加索人;在CX3CRl-V2491和CX3CRI-T280M位点,均明显低于高加索人。结论云南哈尼族人群可能对HIV感染具有较强的抵抗力,能延缓艾滋病的发病进程。     

人类基因组中与HIV-1感染相关的基因多态性及其意义

为探讨ＣＣＲ５、ＣＣＲ２和ＳＤＦ１等位基因的突变和多态性特点,评估不同人群对ＨＩＶ－１感染的遗传易感性,作者收集近年来国际上报道的人类免疫缺陷病毒（ｈｕｍａｎ ｉｍｍｕｎｏｄｅｆｉｃｉｅｎｃｙ ｖｉｒｕｓ－１,ＨＩＶ－１）感染基因相关文献资料,其中包括作者检测的中国人基因组的ＣＣＲ５、ＣＣＲ２和ＳＤＦ１基因多态性的检测结果。通过对比分析,结果显示世界上不同人群的ＨＩＶ－１相关基因的突变和我态性有一     

辽宁汉族人群HLA-DRB1基因多态性分布

目的调查HLA-DRB1基因位点遗传多态性在辽宁汉族人群中的分布。方法应用聚合酶链反应．序列特异性引物方法和反向聚合酶链反应．序列特异性寡核苷酸探针杂交的方法对13265名辽宁汉族人进行中低分辨率HLA-DRB1基因分型。结果共检出HLA-DRB1位点的13种等位基因，其中以HLA-DRB1＊15频率最高（17．49％），其次为HLA-DRB1＊09、＊12和HLA-DRB1＊07，基因频率分别为13．40％、11．87％和11．8l％。HLA-DRB1＊03（18）和HLA-DRB1＊14（8）等位基因未检出。对观察值和期望值进行X^2检验，符合Hardy-Weinberg平衡（X^2=73．34，af=78，P〉0．5）。该人群与南北方汉族人群、日本人、白人和黑人分别进行X^2值检验差异有统计学意义，X^2值分别为112．053、8．514、692．141、70．558和121．755。结论辽宁汉族人群HLA-DRB1基因分布有自身特点。     

中国汉族人群雌激素受体基因多态性及其与血脂关系的研究

目的：研究雌激素受体（ER）基因多态性在中国汉族正常人群中的分布及其与血脂的关系。方法：应用聚合酶链反应（PCR）和限制性片段长度多态性（RFLP）方法,观察118名正常汉族人ER基因型,同时检测血脂并探讨两者的关系。结果：正常汉族人群中ER基因型以xx型、Pp型和Ppxx型出现频率最高,男女间差异不显著,且基因间血脂水平比较差异无显著性（P＞0．05）。与其它种族比较,ER基因型在中国正常人群中的分布与日本、韩国较为接近,而与瑞典、美国、意大利人群中的分布差异显著。结论：ER基因多态性与血脂水平无相关性,但在不同种族间分布有明显的差异,这种差异可能是导致一些疾病在不同种族间的发生、转归和预后不同的遗传因素之一。     

山西汉族正常人群ACE基因多态性频率的分布

目的应用RFLP方法研究ACE基因插入/缺失（I/D）多态性在山西地区360例汉族正常人群中的频率分布。结果显示等位基因频率Ⅰ：62.4%、D：37.6%,各基因型频率分别为：Ⅱ38.1%、ID46.6%、DD13.3%,各基因型频率与新加坡人、日本人、台湾地区、香港的华人接近,与英国白人和非洲籍人群差异显著。表明ACE基因多态性的分布有明显的种族和地区差异。     

中国HIV-1暴露未感染者及感染者趋化因子受体CX3CR1的表达研究

目的 通过分析中国HIV-1暴露未感者（exposed semnegative individuals，ESN）及HIV-1感染者外周血中CX3C1^＋CD8^＋／CD3^＋、CX3CR1^＋CD16^＋／CD3^-、CX3CR1^＋CD56^＋／CD3^-细胞百分率及绝对值的变化，探讨CX3CR1受体与HIV-1感染及疾病进展的关系。方法 采集19例ESN、34例未经治疗的HIV-1感染者及18例健康人抗凝静脉血，采用流式细胞仪检测技术，分析计算三色荧光抗体标记的全血中CX3CR1^＋CD8^＋／CD3^＋、CX3CR1^＋CD16^＋／CD3^-、CX3CR1^＋CD56^＋／CD3^-细胞百分率及绝对值。结果 ESNCX3CR1^＋CD8^＋／CD3^＋细胞的百分率是11．05％±6．52％，绝对值是81．16±13．67个／山，显著高于正常对照组（百分率是5．69％±3．94％，绝对值是37．36±8．28个/μl）；HIV-1感染组CX3CR1^＋CD8^＋／CD3^＋细胞的百分率是20．98％±11．88％，绝对值是166．38±138．38个/μl，显著高于正常对照组。ESN的CX3CR1^＋CD16^＋／CD3^-细胞的绝对值是312．49±159．45个／m，显著高于HIV-1感染组（108．83±119．35个／ta）。ESN的CX3CR1^＋CD56^＋／CD3^-细胞的绝对值是316．98±162．56个叫，显著高于HIV-1感染组（100．27±114．57个／ta）。HIV．1感染者的CX3CR1^＋CD16^＋／CD3^-、CX3CR1^＋CD56^＋／CD3^-细胞的绝对值与CIM^＋T淋巴细胞的绝对值呈明显正相关（P〈0．05）。结论CX3CR1^＋CD8^＋／CD3^＋细胞在中国ESN体内起保护作用，而在HIV-1感染者体内发挥有限的保护作用。表达CX3CR1受体的NK细胞可以作为监测HIV-1感染者免疫状况的一个指标。     

糖皮质激素对BXSB狼疮小鼠肾组织fractalkine/CX3CR1表达的影响

目的：研究BXSB狼疮小鼠肾组织趋化因子fractalkine及其受体CX3CR1的表达以及给予泼尼松治疗后的改变,探讨两者在狼疮肾炎发病机制中的可能作用。方法：12 周龄雄性BXSB狼疮小鼠随机分成泼尼松治疗组（n=6）和实验对照组（n=6）;另取同周龄雄性C57BL/6J小鼠6只作为正常对照组。正常对照组和实验对照组小鼠每天给予0.5 mL生理盐水灌胃;泼尼松治疗组小鼠每天给予0.18 mg/20 g BW的泼尼松溶于0.5 mL生理盐水灌胃。持续10周结束实验。应用逆转录-聚合酶链反应（RT-PCR）及Western印迹检测小鼠肾组织fractalkine和CX3CR1 mRNA和蛋白的表达,并检测小鼠实验室指标以及肾脏组织病理学的变化。结果： BXSB狼疮小鼠肾组织fractalkine以及CX3CR1 mRNA和蛋白表达均较C57BL/6J小鼠明显增高,而经过泼尼松治疗后的BXSB小鼠两者的表达均较未治疗组（实验对照组）明显下降,同时伴有血清免疫球蛋白G（IgG）、IgM、血清抗双链脱氧核糖核酸（dsDNA）抗体水平以及血尿素氮（BUN）、血肌酐（SCr）水平的明显改善,尿蛋白减少;肾小球内免疫复合物沉积和肾脏组织病理学改变亦显著减轻。结论： 实验结果提示fractalkine/CX3CR1可能参与了小鼠狼疮肾炎的发病机制,且糖皮质激素可能通过抑制肾脏fractalkine的表达而发挥其治疗效应。     

Fractalkine/CX3CR1在Ⅳ型狼疮肾炎患者肾组织中的表达

目的： 研究Ⅳ型弥漫增殖型狼疮肾炎、轻微性肾小球病变及正常肾组织中趋化因子fractalkine及其受体CX3CR1的表达，以及与CD68阳性巨噬细胞表达之间的相互关系，探讨fractalkine/CX3CR1在Ⅳ型狼疮肾炎发病中的作用。方法： Ⅳ型狼疮肾炎患者的肾活检组织21例，轻微性肾小球病变患者的肾活检组织18例，光镜下正常的肾组织标本8例。采用免疫组织化学技术检测肾组织中fractalkine、CX3CR1及CD68的表达。结果： （1）正常肾组织和轻微性肾小球病变肾组织中fractalkine基本未见阳性表达；其受体CX3CR1阳性细胞和CD68阳性巨噬细胞仅偶见于肾小球及肾皮质间质中。（2）Ⅳ型狼疮肾炎肾小球和肾皮质间质中CX3CR1阳性细胞和巨噬细胞显著增多，且两者的表达显示高度的相关性（分别为r=0.956，P＜0.01和r=0.965，P＜0.01）。（3）Ⅳ型狼疮肾炎肾组织中fractalkine高表达于皮质肾小管上，fractalkine 阳性皮质肾小管的百分比分别与肾皮质间质CX3CR1阳性细胞数和巨噬细胞数之间高度相关（分别为r=0.720，P＜0.01和r=0.770，P＜0.01）。结论： 提示fractalkine/CX3CR1在Ⅳ型狼疮肾炎的发病机制中可能占有重要地位。     

The cellular microenvironment regulates CX3CR1 expression on CD8+ T cells and the maintenance of CX3CR1+ CD8+ T cells

Expression levels of the chemokine receptor CX3CR1 serve as high-resolution marker delineating functionally distinct antigen-experienced T-cell states. The factors that influence CX3CR1 expression in T cells are, however, incompletely understood. Here, we show that in vitro priming of naïve CD8⁺ T cells failed to robustly induce CX3CR1, which highlights the shortcomings of in vitro priming settings in recapitulating in vivo T-cell differentiation. Nevertheless, in vivo generated memory CD8⁺ T cells maintained CX3CR1 expression during culture. This allowed us to investigate whether T-cell receptor ligation, cell death, and CX3CL1 binding influence CX3CR1 expression. T-cell receptor stimulation led to downregulation of CX3CR1. Without stimulation, CX3CR1⁺ CD8⁺ T cells had a selective survival disadvantage, which was enhanced by factors released from necrotic but not apoptotic cells. Exposure to CX3CL1 did not rescue their survival and resulted in a dose-dependent loss of CX3CR1 surface expression. At physiological concentrations of CX3CL1, CX3CR1 surface expression was only minimally reduced, which did not hamper the interpretability of T-cell differentiation states delineated by CX3CR1. Our data further support the broad utility of CX3CR1 surface levels as T-cell differentiation marker and identify factors that influence CX3CR1 expression and the maintenance of CX3CR1 expressing CD8⁺ T cells.     

Chemokine receptor CX3CR1 promotes dendritic cell development under steady-state conditions

Expression of CX3CR1 is an attribute of myeloid precursors committed to the monocyte/macrophage (Mφ)/DC lineages and is maintained during all stages of DC differentiation. Nevertheless, the exact role of this molecule during developmental progression of myeloid precursors towards the DC lineage remains elusive. To overcome potential compensatory mechanisms and issues of redundancy, we employed competitive adoptive transfer experiments to assess a possible function of CX3CR1 in DC and monocyte/Mφ differentiation in vivo. We show here that expression of CX3CR1 promotes the generation of DCs and monocytes/Mφ under steady-state conditions and during compensatory expansion after selective depletion of DCs, but not under inflammatory conditions evoked by sub-lethal irradiation. Direct administration of CX3CR1-deficient and CX3CR1-sufficient precursors into the spleen or the thymus resulted in a similar competitive advantage of WT over CX3CR1-deficient precursors as i.v. transfer, suggesting that CX3CR1-mediated survival rather than recruitment to lymphoid organs is critical for DC/Mφ differentiation. In conclusion, our data support the hypothesis that CX3CR1 promotes proper development of myeloid precursors into DCs and monocytes/Mφs under steady-state conditions, possibly by providing survival signals or mediating accessibility to organ-specific niches, rather than acting as a mediator of homing to the spleen or the thymus.     

The impact of chemokine receptor CX3CR1 deficiency during respiratory infections with Mycobacterium tuberculosis or Francisella tularensis

Recruitment of immune cells to infection sites is a critical component of the host response to pathogens. This process is facilitated partly through interactions of chemokines with cognate receptors. Here, we examine the importance of fractalkine (CX3CL1) receptor, CX3CR1, which regulates function and trafficking of macrophages and dendritic cells, in the host''s ability to control respiratory infections with Mycobacterium tuberculosis or Francisella tularensis. Following low-dose aerosol challenge with M. tuberculosis, CX3CR1^−/− mice were no more susceptible to infection than wild-type C57BL/6 mice as measured by organ burden and survival time. Similarly, following inhalation of F. tularensis, CX3CR1^−/− mice displayed similar organ burdens to wild-type mice. CX3CR1^−/− mice had increased recruitment of monocytes and neutrophils in the lung; however, this did not result in increased abundance of infected monocytes or neutrophils. We conclude that CX3CR1-deficiency affects immune-cell recruitment; however, loss of CX3CR1 alone does not render the host more susceptible to M. tuberculosis or F. tularensis.     

Interleukin-34 accelerates intrauterine adhesions progress related to CX3CR1+ monocytes/macrophages

Intrauterine adhesions (IUA) are characterized by endometrial fibrosis and impose a great challenge for female reproduction. IL-34 is profoundly involved in various fibrotic diseases through regulating the survival, proliferation, and differentiation of monocytes/macrophages. However, it remains unclear how IL-34 regulates monocytes/macrophages in context of IUA. Here, we showed that the expression level of IL-34 and the amount of CX3CR1+ monocytes/macrophages were significantly increased in endometrial tissues of IUA patients. IL-34 promoted the differentiation of monocytes/macrophages, which express CX3CR1 via CSF-1R/P13K/Akt pathway in vitro. Moreover, IL-34-induced CX3CR1+ monocytes/macrophages promoted the differentiation of endometrial stromal cells into myofibroblasts. Of note, IL-34 caused endometrial fibrosis and increased the amount of CX3CR1+ monocytes/macrophages in endometrial tissues in vivo. IL-34 modulated endometrial fibrosis by regulating monocytes/macrophages since the elimination of endometrial monocytes/macrophages significantly suppressed the profibrotic function of IL-34. Finally, blocking of IL-34 in the LPS-IUA model resulted in the improvement of endometrial fibrosis and decreased number of CX3CR1+ monocytes/macrophages. Our studies uncover the novel mechanism of interaction between IL-34-induced CX3CR1+ monocytes/macrophages and endometrial stromal cells in endometrial fibrosis pathogenesis, and highlight IL-34 as a critical target for treating IUA.