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。     

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。     

云南傣族景颇族人群中与艾滋病相关的CX3CR1基因多态性分布

目的调查HIV-1感染相关的等位基因CX3CR1的单核苷酸多态在我国云南省德宏州傣族、景颇族人群中的分布.方法以101例傣族人群和113例景颇族人群为研究对象,应用聚合酶链式反应-限制性片段长度多态(PCR-RFLP)分析方法,研究CX3CR1基因序列中249和280位点碱基是否发生突变,并对其群体分布、性别分布进行统计学分析.结果中国傣族人群中I249和M280突变基因频率分别为0.0495和0.0297;中国景颇族人群中I249和M280突变基因频率分别为0.0530和0.0221.结论中国云南傣族、景颇族人群存在CX3CR1基因序列中249和280位点突变,突变频率与国内外各种族相比具有一定的可比性.本实验为国内首次对我国傣族、景颇族人群的HIV-1感染协同受体基因CX3CR1进行收集和分析,这在傣族、景颇族人群艾滋病的预防和治疗方面的意义值得深入研究.     

中国人冠心病与载脂蛋白B基因XbaI酶切多态性关联的研究

应用多聚酶链反应研究了１００例正常人和１０３例冠状动脉粥样硬化性心脏病患者ａｐｏＢ基因ＸｂａＩ酶切位点的限制性片段长度多态性。结果表明：冠心病患者和正确人均以Ｘ＾－等位基因为主，绝大多数为纯合子Ｘ＾－Ｘ＾－基因型。     

载脂蛋白B基因可变数目串联重复序列多态性及其与冠心病关联的研究

应用聚合酶链反应研究了１０３例冠心病人和１００例正常人ａｐｏＢ基因３＇端可变数目串联重复序列的多态性。在２０３例受检者中共检出１２种等位基因（３＇β２９─５１）。其中以３＇β３７等位基因最为常见，其次为３＇β３９。等位基因分布的主要形式与来自不同种族的报告基本相似，但等位基因相对频率分布有种族差异。冠心病组中串联重复拷贝数目≥３９的等位基因（３＇ＶＮＴＲ─Ｂ）频率明显高于正常对照组（Ｐ＜０．００１）。同样，冠心病组中３＇β４３以上的等位基因也较正常对照组明显增多（Ｐ＜０．０１）。此外，３＇ＶＮＴＲ－Ｂ等位基因还与血浆ＴＣ、ＬＤＬ─Ｃ水平升高，ＨＤＬ─Ｃ水平降低有关。提示，ａｐｏＢ基因ＶＮＴＲ多态性可能在一定程度上参与冠心病的发生和发展过程。     

冠心病与ACE基因多态性的相关性研究

为研究血管紧张素转移酶（angiotensin coverting enzyme,ACE)基因插入/缺失（insertion/deletion,I/D)多态性与冠心病（coronary artery disease,CAD)的相关性，我们对105例CAD患者{其中50例合并原发性高血压（essential hypertension,EH）}和102例正常人以多聚酶链反应（polymerase chain reaction,PCR)方法检测其ACE基因多态性。发现CAD组（含合并EH）与正常对照组比较，ACE基因型无显著差异，CAD组（不含合并EH）与CAD组（合并EH）比较，ACE基因型无显著差异，CAD组（不含合并EH）或CAD组（合并EH）分别与正常对照组比较，ACE基因型也无显著差异。提示ACE基因I/D多态性与CAD及CAD合并EH均无相关性。     

卵磷脂胆固醇酰基转移酶基因单核苷酸多态性与冠心病脂代谢易感性的关联研究

目的：检测卵磷脂胆固醇酰基转移酶（lecithin cholesterol acyltransferase,LCAT）基因3个编码区单核苷酸多态位点在中国人群中的分布频率，并初步探讨它们与脂代谢和冠状动脉粥样硬化性心脏病（coronary atherosclerotic heart disease,CHD）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方法，分析209名正常人和203例CHD患者中608C／T、911T／C和1188C／T（参照序列：NM_000229）3个位点的多态性。结果：608C和608T等位基因频率分布符合Hardy-Weinberg平衡。CHD患者组608T频率显著低于正常人群（P＝0．034）。与无608T CHD患者相比，具有608T的CHD患者的血浆高密度脂蛋白胆固醇显著升高（P＝0．015）。911T／C和1188C/T在两组中均未检出。结论：LCAT基因608T等位基因与CHD患者较高的血浆高密度脂蛋白胆固醇水平相关联，可能与中国人CHD相关。911T／C和1188C／T在中国人群中非常罕见。     

凝血因子Ⅴ和Ⅶ基因多态性与冠心病的初步研究

目的　观察凝血因子 (coagulation factor ,F )、 (coagulation factor ,F )基因多态性在中国汉族人群中的分布及其与冠心病 (coronary heartdisease,CHD)的关系。方法　应用聚合酶链反应和限制性内切酶片段长度多态性技术检测了 2 34例 CHD患者和 2 10名正常对照者的 F 、F 基因型 ,结合选择性冠状动脉造影结果探讨两者的关系。结果　 F 等位基因 R、Q和 H7、H6频率在冠心病组和对照组分别为 94 .6 %、5 .6 %、70 .3%、2 9.7%和 91.9%、8.1%、6 0 .9%、39.1%。基因型频率符合 Hardy-Weinberg平衡定律。R35 3Q和 HVR4基因型频率和等位基因频率在 CHD组和对照组 ,狭窄血管支数之间比较差异均无显著性。 R35 3Q基因型频率和等位基因频率在非心肌梗塞组和心肌梗塞组比较差异有显著性 (χ2 =4 .711,P<0 .0 5 ,OR=0 .37,95 % CI:0 .15～ 0 .94 ) ,而 HVR4基因多态在两组间比较差异无显著性(χ2 =0 .14 2 ,P>0 .0 5 )。冠心病组和对照组均没有发现 F L eiden突变。结论　F R35 3Q基因多态中的 Q等位基因可能是对抗心肌梗塞的保护因子     

Clif基因多态性与高脂血症的关联分析

目的:探讨Clif基因多态性与高脂血症的关系,为高脂血症的预防及治疗提供新的依据。方法:采用病例-对照研究设计,收集205例高脂血症病例组和281例正常对照组的血液标本和临床资料。通过特异序列聚合酶链反应(SSP-PCR),检测Clifrs2289709,rs62758860的基因多态性与高脂血症的相关性。结果:病例组与对照组比较Clifrs2289709,rs62758860无显著差异(P>0.05)。针对高脂血症进行分型,结果显示Clifrs2289709高脂血症IIb型病例组与对照组相比较,有显著差异性(P<0.05)。结论:Clif基因多态性与高脂血症IIb型存在相关性。     

血管紧张素转换酶基因多态性与壮族人高血压和冠心病关联研究

目的：探讨血管紧张素转换酶（ACE）基因多态性与壮族人原发性高血压、冠心病的易感相关性。方法：应用聚合酶链反应技术测定40例正常汉族人、40例正常壮族人、40例壮族冠心病患者、42例壮族高血压患者的ACE基因I／D多态性领率。结果：①正常壮族人与正常汉族人ACE基因I／D频率差异无显著性（＞0．05）。②壮族人冠心病组、高血压组与正常汉族人、正常壮族人的ACE基因型分布差异有显著性,其D／D型分别为0．475、0．43、0．15、0．175。结论：ACE基因缺失型多态性（DD）可能与壮族人冠心病、高血压的发生有关,可能是其遗传易感性基因标志。     

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。     

Association between polymorphisms in the human chemokine receptor genes CCR2 and CX3CR1 and rheumatoid arthritis

Cell trafficking into the rheumatoid synovium is thought to play an important role in the inflammation seen in rheumatoid arthritis. Chemokine receptors play a central role in this process, and several common variants are known, including the CCR2 variant, CCR2-64I, and two variants of the CX3CR1 gene, V249I and T280M. All three variants result in functional amino acid substitutions. We studied the association of these chemokine receptor variants with susceptibility to and severity of rheumatoid arthritis in two Dutch patient populations; 282 consecutive rheumatoid arthritis patients from a rheumatology outpatient clinic, and a cohort of 101 female rheumatoid arthritis patients, followed closely for a 12-year period, from whom hand and feet X-rays taken at three year intervals were scored and analyzed in this study. Although there was a trend towards increased severity of disease in patients carrying CX3CR1 variants, this was not independent of known risk factors. We found no evidence for a significant independent role for the CCR2 and CX3CR1 variants in the susceptibility to or severity of rheumatoid arthritis.     

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.     

Characterization of fractalkine (CX3CL1) and CX3CR1 in human coronary arteries with native atherosclerosis, diabetes mellitus, and transplant vascular disease

Background: Fractalkine is a novel chemokine that mediates both firm adhesion of leukocytes to the endothelium via CX3CR1 and leukocyte transmigration out of the bloodstream. Fractalkine has recently been shown to play a role in the pathogenesis of acute organ rejection. Since its expression is regulated by inflammatory agents such as LPS, IL-1, and TNF-, fractalkine involvement in atherosclerosis and transplant vascular disease (TVD) is of particular interest. In this study, we characterized the presence of fractalkine and its receptor CX3CR1 in human coronary arteries from normal, atherosclerotic, diabetic, and TVD settings. Method: Polyclonal rabbit antibodies were used to immunostain human fractalkine and CX3CR1 to localize their presence in transverse sections of the proximal left anterior descending and/or right coronary arteries. Slides were scored in a blinded fashion for intensity of staining (0 to 4+) and for localization in vessel walls. Results: Normal coronary arteries showed no fractalkine staining. In atherosclerotic coronary arteries, staining was localized to the intima, media, and adventitia. Within the media, fractalkine expression was seen in macrophages, foam cells, and smooth muscle cells (SMCs). Diabetic vessels showed similar staining patterns to atherosclerotic coronaries, with much stronger staining in the deep intima. Transplanted coronaries showed staining in the endothelium, intima, and adventitia in early disease, and intimal, medial, and adventitial staining in late disease. CX3CR1 staining was seen in the coronary arteries of all cases, with specific localization to regions with fractalkine staining. Conclusion: The distinctive staining patterns in native atherosclerosis, diabetes mellitus with atherosclerosis, and TVD indicate that the expression of fractalkine and CX3CR1 may be important in the pathogenesis of these diseases.     

CX3CR1 polymorphisms and the risk of age-related macular degeneration

Background: Age-related macular degeneration (AMD), a most common eye disease, can lead to irreversible visual impairment. Age, genetic and environmental factors have been implicated in AMD. Chemokine (C-X3-C motif) receptor 1 (CX3CR1) gene polymorphisms could influence the susceptibility of AMD. Methods: We tested the association between AMD and single nocleotide polymorphisms (SNPs) of CX3CR1 gene (rs3732378 and rs3732379) in 102 cases and 115 controls from China. Genotypes were determined by MassArray genotyping assay method. Association between CX3CR1 gene polymorphisms and AMD were examined by χ² test and logistic regression. Results: Genotype distribution of CX3CR1 gene polymorphisms were in accordance with HWE examination. No obvious differences were observed in the genotypes of rs3732378 polymorphism between case and control groups (P>0.05), but A allele of it could increase the risk of AMD (P=0.025, OR=2.391, 95% CI=1.092-5.237). Both TT genotype and T allele of rs3732379 were significantly associated with the susceptibility of AMD (P=8.663, OR=8.663, 95% CI=1.044-71.874; P=0.021, OR=2.076, 95% CI=1.104-3.903). Age, gender and smoking status were used as common confounders to adjust the association between CX3CR1 gene polymorphism and AMD risk. Then we found that rs3732378 had no obvious association with AMD susceptibility. TT genotype of rs3732379 related to the occurrence of AMD, but the association was not significant (P=0.050, OR=8.274, 95% CI=1.002-69.963). T allele of rs3732379 might increase the susceptibility of AMD (P=0.029, OR=2.033, 95% CI=1.077-3.838). Conclusion: T allele of rs3732379 might have a positive association with the susceptibility of AMD.     

CX3CL1 in allergic diseases: not just a chemotactic molecule

Allergic asthma and atopic dermatitis (AD) are two allergic diseases that are primarily driven by the activation of T helper (Th)2 cells. Th2 cells produce cytokines that directly contribute to the symptoms of these diseases. The recruitment and maintenance of Th2 cells into the target tissues are two key events in the pathogenesis of allergic asthma and AD. While migration is mediated by both chemokines and lipid mediators such as leukotrienes and prostaglandins, very little is known about the molecules involved in lymphocyte survival and maintenance in inflamed tissues. However, chemokines could also play a role in this phenomenon. An example of this could be illustrated by CX3CL1, also known as fractalkine. CX3CL1 is a chemokine that is upregulated in some inflammatory diseases including allergic pathologies and that was recently demonstrated to provide a survival signal upon binding to its unique receptor CX3CR1.