Promoter polymorphism of transforming growth factor-β1 gene and ulcerative colitis

AIM： To elucidate the possible difference in two promoter polymorphisms of the transforming growth factor-β1 （TGF-β1） gene （-800G 〉 A, -509C 〉 T） between ulcerative colitis （UC） patients and normal subjects.
METHODS： A total of 155 patients with established ulcerative colitis and 139 normal subjects were selected as controls. Two single nucleotide polymorphisms within the promoter region of TGF-β1 gene （-509C 〉 T and -800G 〉 A） were genotyped using PCR-RFLP. RESULTS： There was a statistically significant difference in genotype and allele frequency distributions between UC patients and controls for the -800G 〉 A polymorphism of the TGF-β1 gene （P 〈 0.05）. The frequency of the TGF-β1 gene polymorphism at position -800 showed that the AA genotype and the allele A frequencies significantly differed between the patients and healthy controls （P 〈 0.05）. At position -509, there was no statically significant difference in genotype and allele frequency between the patients and control subjects.
CONCLUSION： The results of our study indicate that there is a significant difference in both allele and genotype frequency at position -800G 〉 A of TGF-β1 gene promoter between Iranian patients with UC and normal subjects.     

The Association between Myeloperoxidase-463G/A Gene Polymorphism and Coronary Artery Disease

Objectives To study the relationship between myeloperoxidase （MPO）-463G/A polymorphisms and susceptibility to coronary artery disease （CAD） in Han people of north Anhui province. Methods The case group consisted of 79 patients who had all angiographically proven CAD were retrospectively studied. Used polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） methods to decide the genotype of all the patients. Results The frequency of AA homozygotic type in Han people of Anhui province was 1.4%. The risk of CAD for person carrying at least one A allele genotype （ GA and AA） was 0. 37 times of GG genotype. The severity of coronary artery stenosis in CAD patients carrying at least one A allele genotype was 0. 197 times of GG genotype （ P 〈 0. 05 ）. Conclusions The frequency of AA homozygotic type and MPO-463G/A polymorphism in Han people of Anhui province influenced the risk of CAD. A allele had protective function in CAD.     

Association of Fas/Apol gene promoter （-670 A/G） polymorphism in Tunisian patients with IBD

AIM： To detect a possible association between the polymorphism of the （-670 A/G） Fas/Apol gene promoter and susceptibility to Crohn＇s disease （CD） and ulcerative colitis （UC） in the Tunisian population. METHODS： The （-670 A/G） Fas polymorphism was analyzed in 105 patients with CD, 59 patients with UC, and 100 controls using the polymerase chain reaction restriction fragment length polymorphism method. RESULTS： Significantly lower frequencies of the Fas -670 A allele and A/A homozygous individuals were observed in CD and UC patients when compared with controls. Analysis of （-670 A/G） Fas polymorphism with respect to sex in CD and UC showed a significant difference in A/A genotypes between female patients and controls （P corrected = 0.004 ＂in CD patients＂ and P corrected = 0.02 ＂in UC patients＂, respectively）. Analysis also showed a statistically significant association between genotype AA of the （-670 A/G） polymorphism and the ileum localization of the lesions （P corrected = 0.048） and between genotype GG and the colon localization （P corrected = 0.009）. The analysis of IBD patients according to clinical behavior revealed no difference. CONCLUSION： Fas-670 polymorphism was associated with the development of CD and UC in the Tunisian population.     

Promoter polymorphism of transforming growth factor-β1 gene and ulcerative colitis

AIM: To elucidate the possible difference in two promoter polymorphisms of the transforming growth factor-β1 (TGF-β1) gene (-800G > A, -509C > T)between ulcerative colitis (UC) patients and normal subjects.METHODS: A total of 155 patients with established ulcerative colitis and 139 normal subjects were selected as controls. Two single nucleotide polymorphisms within the promoter region of TGF-β1 gene (-509C > T and -800G > A) were genotyped using PCR-RFLP.RESULTS: There was a statistically significant difference in genotype and allele frequency distributions between UC patients and controls for the -800G > A polymorphism of the TGF-β1 gene (P < 0.05). The frequency of the TGF-β1 gene polymorphism at position -800 showed that the AA genotype and the allele A frequencies significantly differed between the patients and healthy controls (P <0.05). At position -509, there was no statically significant difference in genotype and allele frequency between the patients and control subjects.CONCLUSION: The results of our study indicate that there is a significant difference in both allele and genotype frequency at position -800G > A of TGF-β1 gene promoter between Iranian patients with UC and normal subjects.     

Relationship between catecholamine level and gene polymorphism of β1 adrenergic receptor G1165C in children with EV71 infection in hand foot and mouth disease

Objective:To investigate the relationship between the levels of plasma adrenaline and norepinephrine and gene polymorphism of β1 adrenergic receptor G1165 C in children with enterovirus 71(EV71) infection in hand foot and mouth disease(HFMD). Methods:The polymerase chain reaction(PCR) was used to detect the expression of gene polymorphism of β1 adrenergic receptor G1165 C in vitro. The levels of plasma adrenaline and norepinephrine were measured by enzyme-linked immunosorbent assay(ELISA). Results:The plasma norepinephrine level of severe group was significantly higher than the mild group in children with EV71 infection in HFMD(P0.05); however,the levels of plasma adrenalinein in two groups had no statistical differences(P0.05); There was no significant difference in the distribution of β1 adrenergic receptor G1165 C genotype and allele between EV71 infection group and healthy control group(P 0.05). Further analysis of EV71 infection group by dividing it into mild and severe groups showed that there was no significant difference in the distribution of genotype and allele between these two groups as well(P 0.05). There was no significant difference in the levels of epinephrine and norepinephrine in different genotypes of EV71 infection group(P 0.05),and in the levels of plasma epinephrine and norepinephrine in the mild and severe groups(P 0.05). Conclusions:As the disease gets worse,the plasma norepinephrine level has a rising trend in children with EV71 infection in HFMD,which is an important indicator to evaluate the progress of the disease. However,the gene polymorphism of eptor G1165 C have no significant correlation,not only with the susceptibility and severit β1 adrenergic recy of EV71 infection in hand,foot and mouth disease,but also with the levels of catecholamine.     

Relationship between β-fibrinogen gene - 455G/A,- 148C/T polymorphisms and atrial fibrillation with cerebral infarction

Objective To investigate the relationship between β-fibrinogen (β-Fg) gene -455G/A,- 148C/T polymorphisms and atrial fibrillation (AF) with cerebral infarction.Methods Polymerase chain reaction-restriction fragment length polymorphism was used to detect the genotypes of -455G/A and -148C/T in 97 patients with AF with cerebral infarction (AF with cerebral infarction group),80 patients with AF alone (AF group),and 98 health subjects (healthy control group).Results The A allele frequencies of -455G/A in the AF with cerebral infarction group and the AF group were 0.304 and 0.344 respectively.They were significantly higher than 0.179 in the healthy control group (all P＜0.05).The T allele frequencies of - 148C/T in the AF with cerebral infarction group and the AF group were 0.348and 0.369,respectively.They were significant higher than 0.240 in the healthy control group (all P＜0.05).Conclusions The A allele of -455G/A and the T allele of -148C/T were associated with AF with cerebral infarction and AF.     

Tag single nucleotide polymorphism rs1532624 located in cholesteryl ester transfer protein gene is associated with atherosclerosis cerebral ischemia

Objective: To investigate the relationship between polymorphisms of rs1532624 and rs289741 loci in cholesteryl ester transfer protein(CETP) genes and atherosclerotic cerebral infarction(ACI). Methods: The CETP gene rs1532624 and rs289741 in 95 patients with ACI and 177 healthy subjects were genotyped by Mass ARRAY mass spectrometry. Each locus genotype and allele frequency distributions were compared. Results: The difference of allele frequency distribution between the rs1532624(χ~2=1.723, P=0.189) and rs289741(χ~2=2.466, P=0.116) were not statistically significant. The frequency distribution of rs1532624 genotype between the cerebral infarction group and healthy control group was statistically significant(χ~2=7.096, P=0.029), while rs289741 genotype frequency distribution between the two groups was not statistically significant(χ~2=2.906, P=0.234). Conclusion: ACI have a positive correlation with rs1532624 polymorphism, and AA genotype may be susceptible factors of ACI.     

Relationship between IFN-γ gene polymorphism and susceptibility to intrauterine HBV infection

AIM: To explore the susceptibility of children to intrauterine HBV infection by studying the relationship between IFN-y gene polymorphism, including IFN-γ 874A/T single nucleotide polymorphism(SNP) and CA repeat microsatellite polymorphism and intrauterine HBV infection. METHODS: A TaqMan fluorescence polymerase chain reaction in the IFN-γ 874A/T single nucleotide polymorphism was tested in the intrauterine HBV infection group(group I) and the normal immune children group(group II). Capillary electrophoresis was performed in the above two groups to assay the IFN-γCA repeat microsatellite polymorphism. RESULTS: Frequencies of AA, AT and TT genotypes were 67.4%, 19.6% and 13.0% in the intrauterine HBV infection group, and 45.2%, 30.1% and 24.7% in the normal immune children group, respectively. A significant difference was found in the frequency distribution of IFN-γ 874 genotype between the two groups (X2 = 5.102, P= 0.02389). In the intrauterine HBV infection group the AA genotype was more common than in the normal immune group. Frequency of IFN-γ 874A allele was 77.17% in the intrauterine HBV infection group, and 60.27% in the normal immune children group. In the intrauterine HBV infection group the IFN-γ 874A allele was more common than in normal immune group. A significant difference was found in the frequency distribution between the two groups (X2 = 7.238, P = 0.02389, OR= 2.228, 95% CI = 1.244-3.992). (CA12) /(CA12) of IFN-γCA microsatellite polymorphism was 11.90% in the intrauterine HBV infection group and 26.47% in the normal immune children group. A significant difference was found in the frequency distribution between the two groups (X2 = 5.64, P = 0.0176). Frequency of IFN-γCA repeat was 25% in the intrauterine HBV infection group and 43.38% in the normal immune children group. The frequency of IFN-γCA repeat was less in the intrauterine HBV infection group than in normal immune group. A significant difference was found in the frequency distribution between the two groups (X2 = 7.548, P= 0.0060). CONCLUSION: There is a relationship between IFN-γ 874A/T SNP and intrauterine HBV infection as well as between IFN-γCA microsatellite polymorphism and intrauterine HBV infection. IFN-γgene polymorphism might be important in determining individual's susceptibility to intrauterine HBV infection.     

The clinical relevance of MBL2 gene polymorphism and sepsis

Objective:To detect the clinical relevance of mannose-binding lectin 2(MBL2) gene polymorphism and sepsis in Chinese lived in Hainan island.Methods: Blood samples from 57 patients with sepsis and 69 patients without sepsis were collected in the ICU of several large hospitals in Hainan province. Genomic DNA was extracted from whole blood and then PCR purification product was sequenced and typed by 3730 sequencing analyzer. The concentration of MBIL2 in serum was detected by ELISA.Results: We found that genotype and allele distributions in two groups were in accordance with the Hardy-Weinberg Equilibrium. The frequency of GA genotype was significantly higher than that in non-sepsis group(P=0.013). A allele frequency in sepsis group was also much higher than that in non-sepsis group(P=0.028).Logister regression analysis showed that the patients who carried A allele were more prone to get sepsis than G allele carrier(P=0.014, OR=2,550, 95%CI=1.207-5.386). The MBL2 level in serum of sepsis patients with genotype GG and GA was significantly lower than that in non-sepsis group(P0.05). In sepsis group, the MBL2 serum level of patients with genotype GA was obviously lower than that in patients with genotype GG(P0.05).Conclusions: The variation of rs 1800450 G→A increased the incidence of sepsis and decreased the level of MBL2 in serum.     

Association of polymorphisms of IL and CD14 genes with acute severe pancreatitis and septic shock

IM: To investigate IL-1β+3 594 in the 5th intron, IL-10-1 082 and CD14-159 polymorphisms in patients with acute pancreatitis (AP) and septic shock. METHODS: The study included 215 patients (109 with acute severe pancreatitis (SAP), 106 with acute mild pancreatitis (MAP)) and 116 healthy volunteers. Genomic DNA was prepared from peripheral blood leukocytes. Genotypes and allele frequencies were determined in patients and healthy controls using restriction fragment length polymorphism analysis of PCR products. RESULTS: The frequencies of IL-1β+3 594T, IL-10-1082G and CD14-159T allele were similar in patients with mild or severe pancreatitis and in controls. Within SAP patients, no significant differences were found in the allele distribution examined when etiology was studied again. Patients with septic shock showed a significantly higher prevalence of IL-10-1082G allele than those without shock (X2 = 5.921, P=0.015). CONCLUSION: IL-10-1082G plays an important role in the susceptibility of SAP patients to septic shock. Genetic factors are not important in determination of disease severity or susceptibility to AP.     

Is the monocyte chemotactic protein-1 -2518 G allele a risk factor for severe acute pancreatitis?

BACKGROUND & AIMS: Acute pancreatitis (AP) reflects the intensity of the inflammatory response and is divided into mild AP (MAP) or severe AP (SAP). Monocyte chemotactic protein-1 (MCP-1) gene expression is altered by an A/G polymorphism (-2518), with the G allele increasing MCP-1 production. Our aim was to determine whether the MCP-1 -2518 A/G polymorphism affects the severity of AP. METHODS: Seventy-seven consecutive patients and 116 controls were evaluated. The A/G genotype was evaluated by polymerase chain reaction amplification, restriction fragment length polymorphism, and DNA sequencing. MCP-1 serum levels were quantified using a fluorescence bead-based immunoassay. RESULTS: Sixty-three of 77 patients had MAP (82%) and 14 of 77 had SAP (18%). Patients with SAP had a significantly greater proportion of the G allele (12 of 14; 86%) than did control subjects (50 of 116; 43%) (odds ratio [OR], 7.9; 95% confidence interval [CI], 1.7-37, P < .003) or MAP patients (29 of 63; 46%) (OR, 7.0; 95% CI, 1.5-34; P < .007). Patients with pancreatitis and AA genotype had a low risk for SAP (OR, .13; 95% CI, .01-.61; P < .003). As predicted by the genotype, the serum MCP-1 levels were significantly higher in the SAP patients when compared with the MAP patients ( P = .002) and they also predicted death. CONCLUSIONS: MCP-1 -2518 G allele is a risk factor for severe AP. MCP-1 serum levels, measured early in the course of AP, appear to be an accurate predictor of severity of acute pancreatitis and death.     

MCP-1基因多态性与老年2型糖尿病患者并发肾功能衰竭的相关性研究

目的 探讨单核细胞趋化蛋白-1(MCP-1)基因-2518A/G多态性与老年2型糖尿病患者并发肾功能衰竭之间的相关性.方法 采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测56例2型糖尿病伴肾功能衰竭患者及56例2型糖尿病(无肾损伤)患者、50名健康对照者的MCP-1基因-2518位点的基因型分布及基...     

单核细胞趋化蛋白-1基因多态性与冠状动脉介入治疗后再狭窄的相关性研究

目的 探讨单核细胞趋化蛋白-1(MCP-1)启动子区-2518A/G基因多态性与冠状动脉(冠脉)粥样硬化病变进程及经皮冠脉腔内成形术(PCI)后再狭窄的相关性.方法 对276例接受PCI并进行冠脉造影随访的患者,采用PCR-RFLP方法进行MCP-1 -2518A/G多态性检测;按冠脉造影结果分为再狭窄组(113例)和无再狭窄组(163例),判定冠脉血管病变及再狭窄与MCP-1 -2518A/G多态性的相关性.结果 MCP-1 -2518A/G基因型频率为:AA纯合子21.0%,GG纯合子34.1%,AG杂合子44.9%,3种基因型血管病变支数和血管平均狭窄程度,差异均无统计学意义(P＞0.05).再狭窄组中AA、AG和GG基因型频率分别为23.9%、40.7%和35.4%,无再狭窄组分别为19.0%、47.9%和33.1%,差异无统计学意义(P=0.446).再狭窄组中-2518A和G等位基因频率分别为44.2%和55.8%,无再狭窄组分别为42.9%和57.1%,差异无统计学意义(P=0.761).结论 冠脉粥样硬化进程及PCI术后再狭窄可能与MCP-1 -2518A/G基因多态性无相关性.     

Monocyte chemoattractant protein 1 (MCP-1) gene polymorphism is not associated with severe and cerebral malaria in Thailand

The pathogenesis of cerebral malaria from Plasmodium falciparum infection is thought to involve inflammation of the central nervous system. Since monocyte chemoattractant protein 1 (MCP-1) is a chemokine strongly involved in the inflammatory process, we here study MCP-1 gene polymorphisms in association with severe or cerebral malaria in Thailand. Malaria patients in the northwest of Thailand were grouped into mild (n=206), severe (165), and cerebral (110) malaria case groups. Five single nucleotide polymorphisms (SNPs) in the promoter (-2518A/G, -2348G/C, -2158C/T, -2076A/T, and -2072T/C), and 1 SNP in intron 1 (764C/G) were analyzed by PCR-RFLP, PCR-SSP, or direct sequencing. The SNP -2158 was a novel polymorphism found in this study. For all SNPs, genotype and allele frequencies were not significantly different between mild and severe or mild and cerebral malaria. Strong linkage disequilibrium was found among 4 SNPs (-2518A/G, -2348G/C, -2076A/T, and 764C/G), resulting in 4 major estimated haplotypes. The most common haplotype was GGAC. The results indicated that MCP-1 gene polymorphisms were not associated with malaria severity, implying that MCP-1 was not a cause of malaria severity in this Thai population.     

白细胞介素-10启动子-1082和-819位点基因多态性与肠易激综合征的关系

目的 探讨白细胞介素(IL)-10启动子区基因多态性与肠易激综合征(IBS)的关系.方法 采用聚合酶链式反应结合限制性片段长度多态性分析(PCR-RFLP),对313例IBS患者及281名对照者的1L-10启动子区-1082及-819位点进行基因型分析.结果 在-1082位点与-819位点,IBS组、对照组和总人数组中,各基因型的分布符合Hardy-Weinberg平衡规律.IL-10-819位点T等位基因频率腹泻型(79.8％)和混合型(77.1％)显著高于对照组(65.7％,P＜0.05).IL-10-1082位点A、G等位基因频率在各亚型与对照组间差异无统计学意义(P＞0.05),腹泻型与混合型间差异有统计学意义(P＜0.05).IBS组-819位点T/T基因型频率(51.1％)显著高于对照组(40.2％),C/T基因型显著低于对照组,差异均有统计学意义(P值均＜0.05);-819位点T/T基因型频率IBS的各亚型组显著高于对照组,C/T基因型IBS各亚型显著低于对照组,差异均有统计学意义(P值均＜0.05);C/C基因型在各亚型间差异无统计学意义(P＞0.05).-1082位点基因型在IBS组和对照组间的差异无统计学意义(P＞0.05);IBS腹泻型的-1082位点A/A基因型(93.3％)显著高于混合型IBS(82.4％),A/G基因型低于混合型IBS,差异均有统计学意义(P值均＜0.05);但IBS其他亚型间以及与对照组间差异无统计学意义(P＞0.05).结论 IL-10启动子区域-819位点T/T基因型可能与IBS发生有关,而-1082位点可能与IBS发病无关.     

Monocyte chemoattractant protein-1 (MCP-1) 2518G/A gene polymorphism in Turkish type 2 diabetes patients with nephropathy

Tissue macrophage accumulation is thought to induce insulin resistance during obesity and stimulate the progression of diabetic nephropathy (DN). The objective of this study was to investigate genotypic and allelic frequencies of monocyte chemoattractant protein-1 (MCP-1) gene polymorphism in the healthy and patients with and without DN. The MCP-1 genotypes were determined in 43 patients with nephropathy and 43 without nephropathy and a control group of 105 healthy individuals. The genotype MCP-1 (-2518G/A) distribution did differ between the control group and the type 2 diabetic patients (P?=?0.004). The frequency of the polymorphic G allele was also no similar for the group with type 2 diabetes as for the control group with 20.9 and 32.4%, respectively (P?=?0.012). The AA genotype and A allele at MCP-1 -2518 was an independent risk factor for the progression of type 2 diabetes. In conclusion, MCP-1 AA genotype and A allele may play a specific role(s) in determining diabetic susceptibility, but do not seem to be important in the clinical manifestations of DN.     

几种趋化性细胞因子及受体基因多态性与系统性红斑狼疮的关联研究

目的探讨基质衍生因子1-3'A(stromalcell-derivedfactor1-3'A,SDF1-3'A)、趋化性细胞因子受体2-64I(chemoattractantcellreceptor2-64I,CCR2-64I)190位点、单核趋化蛋白1(monocytechemoattractantprotein-1promoter-2518polymorphism,-2518MCP-1)基因多态性及其交互作用与系统性红斑狼疮(SLE)的相关性。方法以143例SLE病人和157名健康对照为对象进行病例对照研究。应用聚合酶链反应—限制性内切酶片段长度多态性(polymerasechainreaction/restrictionfragmentlengthpolymor-phism,PCR-RFLP)方法确定SDF1-3'A和-2518MCP-1基因多态性,应用突变特异性扩增系统(amplifica-tionrefractorymutationsystem,ARMS)确定CCR2-64I基因多态性。结果-2518MCP-1、CCR2-64I、SDF1-3'A等位基因及基因型频率在SLE和健康对照组之间差异无显著性。但-2518MCP-1A/G基因型对照组高于病例组(χ2=4.11,P=0.04)。基因间交互作用分析发现,当SDF1-3'A、-2518MCP-1、CCR2-64I基因型分别为G/G、A/G和G/G时,对SLE发病可能具有保护作用(P<0.05)。其他基因型间均未见交互作用(P>0.05)。结论单个-2518MCP-1、CCR2-64I、SDF1-3'A基因多态性与SLE易感性无关联,但他们之间可能存在交互作用。     

单核细胞趋化蛋白-1基因多态性与肺结核易感性的关系

目的 探讨中国汉族人群单核细胞趋化蛋白-1(MCP-1)基因-2518位点多态性与肺结核发病的关系.方法 2008年3-8月采用1:1配对病例对照设计,用PCR-限制性片段长度多态性分析(RLFP)检测167例肺结核患者和167例对照的MCP-1基因-2518位点的基因型分布.病例组年龄16～77岁,对照组年龄15～78岁,两组患者的中位年龄均为43岁,四分位间距均为30岁;两组均为男110例、女57例,汉族.对一般情况、现病史、既往病史及肺结核相关环境因素进行问卷调查,并进行单因素和多因素条件logistic回归分析.结果 AA、GA和GG基因型在病例组的分布频率分别为21/167(12.6%)、62/167(37.1%)和84/167(50.3%),在对照组的分布频率分别为42/167(25.2%)、83/167(49.7%)和42/167(25.1%).单因素分析结果显示,基因型在病例组和对照组中分布频率的差异有统计学意义(x2=24.041,P<0.01);调整环境因素后,多因素回归分析结果显示,GG基因型与肺结核发病仍有显著性相关性(OR=1.989,95%CI为1.154～3.428,x2=6.124,P<0.05).结论 MCP-1基因-2518位点GG基因型可能与中国汉族人群的肺结核易感性有关.     

Monocyte chemoattractant protein-1: plasma concentrations and A(-2518)G promoter polymorphism of its gene in systemic lupus erythematosus

OBJECTIVE: To determine (1) whether the A(-2518)G polymorphism of CCL-2, the gene encoding monocyte chemoattractant protein-1 (MCP-1), is associated with disease, MCP-1 concentration, nephritis, or coronary artery calcification (CAC) in systemic lupus erythematosus (SLE); and (2) whether MCP-1 and homocysteine (Hcy) concentrations are correlated. METHODS: Statistical tests were applied to determine the relationships between CCL-2 A(-2518)G genotypes, plasma MCP-1 concentrations, and clinical variables in Caucasian and African American patients with SLE and controls. RESULTS: The CCL-2 (-2518)G allele was not significantly associated with SLE in the whole study sample (p = 0.07). Among Caucasians, but not African Americans, G allele carriers had significantly increased risk of SLE (OR 4.2, 95% CI 1.8-9.6, p < 0.0001). Genotype was not associated with nephritis, CAC, or MCP-1 concentrations when all patients or all controls were considered; however, among recently diagnosed patients, G allele carriers had significantly higher MCP-1 concentrations than AA homozygotes (p = 0.02). SLE patients had higher MCP-1 concentrations than controls (p < 0.0001), African American patients had higher concentrations than Caucasian patients (p = 0.006), and patients with nephritis had higher concentrations than those without nephritis (p = 0.02). Although not associated with CAC, MCP-1 concentrations were significantly positively correlated with Hcy. CONCLUSION. CCL-2 A(-2518)G genotype is a significant risk factor for SLE among Caucasians but not African Americans, suggesting that genetically mandated differences in MCP-1 expression contribute to SLE etiology in the former. The positive correlation between MCP-1 and Hcy concentrations is consistent with the hypothesis that active inflammation and hyperhomocysteinemia are etiologically linked.     

Monocyte chemoattractant protein-1 (MCP-1) gene polymorphism and risk of Alzheimer's disease in Italians

Monocyte chemoattractant protein-1 (MCP-1) is a key molecule for monocyte chemotaxis and tissue extravasation and for the modulation of leukocyte function during inflammation. Upregulation of MCP-1 may occur in the brain of subjects affected by Alzheimer's disease (AD) and MCP-1 levels in plasma and cerebrospinal fluid have been proposed as biological markers for the inflammatory process that accompanies AD pathogenesis. Importantly, serum levels and biological activity of MCP-1 protein are strongly influenced by a single nucleotide polymorphism occurring at position -2518 of the MCP-1 gene promoter. A recent study has investigated the possible association between this gene polymorphism and AD in a Spanish population, with negative results. Here, we performed a case-control study to test whether the risk for AD might be influenced by the -2518 A/G polymorphism of the MCP-1 gene in an ethnically homogeneous Italian population. The GG genotype and the G allele of the MCP-1 gene polymorphism were significantly more common in the AD group than in control individuals (P<0.0001) A logistic regression analysis indicated that the GG genotype was an independent risk factor for AD in our population. This effect was not influenced by the presence of the APOE 4 high-risk allele, nor by the presence of other gene variations associated with a pro-inflammatory phenotype. These findings indicate that the -2518 A/G polymorphism of the MCP-1 gene is associated with AD in Italians and confirm that inflammatory gene variations may be important contributors in the development and progression of neurodegenerative disorders.