The -2518A/G polymorphism in the monocyte chemoattractant protein-1 (MCP-1) gene and diabetes risk: a meta-analysis

We conducted a meta-analysis to investigate the association between the −2518A/G polymorphism in the MCP-1 gene and the risk of diabetes. Ten case-control studies were included in this meta-analysis. Results indicated this polymorphism may be a risk factor for diabetes in Caucasians. Future studies are needed to validate our conclusions.     

Association of the MCP-1 gene polymorphism A-2518G with carpal-tunnel syndrome in hemodialysis patients

Abstract

Carpal-tunnel syndrome (CTS) in long-term hemodialysis patients is caused by the deposition of amyloid as well as by the local inflammatory process. The recruitment of monocytes/macrophages in the tenosynovium, promoted by chemokines such as monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1a (M1P-I α), is thought to play an important role in CTS development. The genetic polymorphism of these chemokines has been identified and their clinical function has been partly revealed. We attempted to analyze the relationship between these polymorphisms and their susceptibility to CTS. The subjects of this study were 366 patients who underwent hemodialysis. Ninety-five patients received surgery for CTS. No significant difference was observed in the genotype distributions of MCP-1 or MIP-lα between patients who received CTS surgery and those that did not. However, with the use of a logistic regression model, the MCP-1 GG genotype was identified as a risk factor for the development of CTS, in addition to the duration and the age of initiation of dialysis, as confirmed by a Cox proportional hazards model. In conclusion, homozygosity for G at -2518 in the MCP-1 gene might be a candidate for the genetic marker of CTS development in Japanese hemodialysis patients.     

急性心肌梗死患者血清MCP-1水平及其与MCP-1 2518G/A多态性的关系

目的探索中国苏北涟水县汉族人群急性心肌梗死(AMI)患者血清单核细胞趋化蛋白1(MCP-1)水平及其与MCP-1 2518G/A多态性的关系。方法 73例无冠状动脉病变者(对照组)和94例AMI患者(AMI组)的血清MCP-1水平采用ELISA检测,MCP-1 2518G/A多态性采用PCR-RFLP、DNA测序技术方法检测。结果血清MCP-1水平(以M/IQR表示)在AMI组为186.24/285.15 ng/L,显著高于对照组的100.71/134.02 ng/L(P=0.001)。多元线性回归分析显示,血清MCP-1水平与男性负相关,与高血压、糖尿病、吸烟正相关,与老龄和血脂异常无明显相关。经校正高血压、糖尿病、年龄、性别、吸烟和血脂水平等因素后,≥75%分位数的血清MCP-1水平与AMI的发病风险呈正相关(OR=2.764,95%CI为1.061~7.204,P=0.037)。MCP-1 2518G/A基因型分布和等位基因频率在AMI组与对照组之间无显著差异(P0.05),血清MCP-1水平在对照组、AMI组各基因型间无显著差异(P0.05)。结论中国苏北涟水县汉族人群的AMI患者血清MCP-1水平显著高于对照者;血清MCP-1水平受性别、高血压、糖尿病、吸烟影响,但≥75%分位数的血清MCP-1水平是AMI的独立预测因素;MCP-1 2518G/A多态性不增加AMI的易感性,也不影响MCP-1血清水平。     

Association between the CD209 promoter -336A/G polymorphism and susceptibility to tuberculosis: a meta-analysis

Background and objective: Dendritic cell‐specific intracellular adhesion molecule‐3 grabbing nonintegrin (DC‐SIGN), encoded by the CD209 gene, is a major Mycobacterium tuberculosis receptor on human dendritic cells. The potentially functional ?336A/G polymorphism in the CD209 promoter region has been associated with susceptibility to tuberculosis (TB), but the results have been inconclusive. We performed a meta‐analysis to clarify the relationship between the CD209?336A/G variant and the risk of TB. Methods: Ten studies involving a total of 2598 TB patients and 2614 control subjects were systematically reviewed, and the data were quantitatively synthesized by meta‐analysis. The Q‐test was applied to assess the heterogeneity of associations among the studies, and Egger's regression test was used to assess potential publication bias. Results: No significant association was identified between the CD209?336A/G polymorphism and risk of TB (G allele vs A allele: odds ratio (OR) 1.02, 95% confidence interval (CI) 0.90–1.15). Moreover, no significant association was observed in populations of African ethnicity (OR 1.01, 95% CI 0.87–1.17) or among individuals who were negative for the human immunodeficiency virus (OR 0.98, 95% CI 0.84–1.15). Conclusions: This meta‐analysis has indicated that the CD209?336A/G polymorphism may not contribute to susceptibility to TB.     

Association of the MCP-1 gene polymorphism A-2518G with carpal-tunnel syndrome in hemodialysis patients.

Carpal-tunnel syndrome (CTS) in long-term hemodialysis patients is caused by the deposition of amyloid as well as by the local inflammatory process. The recruitment of monocytes/macrophages in the tenosynovium, promoted by chemokines such as monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1alpha (MIP-1alpha), is thought to play an important role in CTS development. The genetic polymorphism of these chemokines has been identified and their clinical function has been partly revealed We attempted to analyze the relationship between these polymorphisms and their susceptibility to CTS. The subjects of this study were 366 patients who underwent hemodialysis. Ninety-five patients received surgery for CTS. No significant difference was observed in the genotype distributions of MCP-1 or MIP-1alpha between patients who received CTS surgery and those that did not. However, with the use of a logistic regression model, the MCP-1 GG genotype was identified as a risk factor for the development of CTS, in addition to the duration and the age of initiation of dialysis, as confirmed by a Cox proportional hazards model. In conclusion, homozygosity for G at -2518 in the MCP-1 gene might be a candidate for the genetic marker of CTS development in Japanese hemodialysis patients.     

单核细胞趋化蛋白-2518G/A基因多态性与冠心病的关系

目的研究单核细胞趋化蛋白-1（MCP-1）-2518G／A基因多态性对冠心病发病的影响。方法选取冠心病患者300例,正常对照组60例。冠心病患者分急性冠状脉综合征（ACS）组180例以及稳定型心绞痛（SAP）组120例。所有患者行冠状动脉造影（CAG）检查,采用Gensini评分。酶联免疫法测定MCP-1浓度,PCR-RFLP方法检测MCP-1-2518G／A位点多态性,研究MCP-1-2518G／A基因多态性与冠心病的相关性。结果（1）MCP-1-2518G／A基因多态性ACS组GG型基因和G等位基因频率分布较SAP组及正常对照组升高[GG型基因：ACS组（33．4％）,SAP组（24．2％）,对照组（15．0％）。P〈0．05;G等位基因频率：ACS组（51．1％）,SAP组（40．4％）,对照组（31．7％）,P〈0．05],ACS组AA型基因及A等位基因较SAP组及正常对照组降低[AA型基因：ACS组（31．1％）,SAP组（43．3％）,对照组（51．7％）,P〈O．05;A等位基因频率：ACS组（48．9％）,SAP组（59．6％）,对照组（68．3％）,P〈0．05]。（2）三种基因型间MCP．1浓度比较,GG型MCP-1浓度较AG型及AA型升高[GG型基因：（153±22）ng／L,AG型基因：（136±18）ng／L,AA型基因：（124±15）ng／L,（P〈0．05）]。（3）多元回归分析冠脉病变Gensini评分与低密度脂蛋白-胆固醇、空腹血糖、MCP-1GG型基因成正相关（P〈0．05）,高密度脂蛋白-胆固醇与冠状动脉狭窄程度呈负相关（P〈0．05）。结论MCP-1-2518G／A基因多态性与冠心病严重程度相关;MCP-1-2518G／A基因多态G等位基因能通过增强MCP-1表达参与冠心病发病。     

活化T细胞核因子和单核细胞趋化蛋白-1及该蛋白2518G/A基因多态性与冠心病的关系

目的:研究活化T细胞核因子和单核细胞趋化蛋白-1及该蛋白2518G/A基因多态性与冠心病病变程度的相关性。方法:选取冠心病患者300例,根据冠状动脉(冠脉)造影结果确诊为冠心病的患者分为急性冠脉综合征(ACS)组180例,稳定型心绞痛组120例。另选冠脉造影正常者为对照组60例。应用Gensini评分评定狭窄程度,酶联免疫法测定活化T细胞核因子(NFAT)、单核细胞趋化蛋白-1(MCP-1)浓度,多聚酶链反应--末端限制性片段长度多样性(PCR-RFLP)方法检测MCP-1 2518G/A基因多态性。结果:①急性冠脉综合征组的NFAT、MCP-1浓度显著高于稳定型心绞痛组及对照组,差异有统计学意义(P<0.05),MCP-1浓度与NFAT呈正相关(r=0.65,P<0.05)。②冠脉病变Gensini评分与NFAT、MCP-1、低密度脂蛋白胆固醇、血糖呈正相关,与高密度脂蛋白胆固醇呈负相关。③MCP-1 2518G/A基因有三个基因型,GG型的MCP-1浓度较AG型及AA型升高(P<0.05),ACS组GG型基因和G等位基因频率较稳定型心绞痛组及对照组增高,差异均有统计学意义(P<0.05)。结论:冠心病患者血浆NFAT与MCP-1水平的升高及MCP-1 2518G/A基因多态性与冠脉病变程度相关。     

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.     

Genetic polymorphism of MCP-1-2518, IL-8-251and susceptibility to acute pancreatitis： A pilot study in population of Suzhou, China

AIM： To study the relationship between MCP-1-2518A/ G, IL-8-251A/T polymorphism and acute pancreatitis （AP） in the Han population of Suzhou, China.
METHODS： A case-control study was conducted to compare the distribution of genotype and genetic frequency of MCP-1-2518A/G, IL-8-251A/T gene polymorphism among AP （n = 101）, including mild AP （n = 78） and severe AP （n = 23） and control healthy individuals （n = 120） with polymerase chain reaction- restriction fragment length polymorphism （PCR-RFLP） and DNA sequencing, and analyze the relationship between the MCP-1-2518A/G, IL-8-251A/T gene polymorphism and the susceptibility to AP.
RESULTS： Significant differences were found in the distribution of genotype of MCP-1-2518A/G between the healthy control group and mild AP group （χ^2 = 32.015, P 〈 0.001）, the same was evident between the healthy control group and severe AP group （χ^2 = 12.932, P 〈 0.05） in Suzhou. However, no difference of genotypic distribution was noted between MAP and SAP （Z2 = 0.006, P = 0.997）. The genetic frequencies of G allele in mild AP were 72.4% （113/156） and 76.1% （35/46） in severe AP, both were higher than the controls, 47.1% （113/240） （χ^2 = 24.804; P 〈 0.001, and 4,2 = 13：005; P 〈 0.001）, but no difference was found between severe AP and mild AP （χ^2 = 0.242, P = 0.623）. No difference was found in the distribution of genotype of IL-8-251A/T between the healthy control group and AP group neither in the frequency of A and T allele.
CONCLUSION： The MCP-1-2518 AA genotype of the population in Suzhou may be a protective genotype of AP, while one with higher frequency of G allele is more likely to suffer from pancreatitis. But the genotype of AA and the frequency of G allele could not predict the risk of severe AP. No correlation is found between the IL-8-251 polymorphism and the liability of AP.     

Association of NOD1 (CARD4) insertion/deletion polymorphism with susceptibility to IBD: A meta-analysis

AIM: To find evidences about whether NOD1/CARD4 insertion/deletion polymorphism is associated with inflammatory bowel disease by meta-analysis. METHODS: We surveyed the studies on the association of NOD1/CARD4 insertion/deletion polymorphism with inflammatory bowel disease in PubMed. Meta-analysis was performed for genotypes GG/T vs T/T, GG/GG vs T/T, GG/T + GG/GG vs T/T, GG/GG vs T/T + GG/T, and GG allele vs T allele in a fixed/random effect model. RESULTS: We identified 8 studies (6439 cases and 4798 cont...     

MCP-1 gene A-2518G polymorphism and carotid artery atherosclerosis in patients with type 2 diabetes

AimsCardiovascular diseases are the major cause of mortality in patients with diabetes mellitus. Monocyte chemoattractant protein-1 (MCP-1) is a potent chemokine and plays an important role in cardiovascular diseases. The objective of this study was to evaluate the relation between the genotypes of the MCP-1 A-2518G polymorphism and the development of carotid atherosclerosis in patients with type 2 diabetes.MethodsThe subjects were 303 unrelated patients who were diagnosed with type 2 diabetes mellitus. To evaluate macroangiopathy, we measured carotid artery intima-media thickness (IMT) by ultrasonography. The MCP-1 A-2518G polymorphism was determined by TaqMan PCR method.ResultsIMT in patients with the MCP-1 −2518 AG or GG genotype was significantly greater than the AA-genotype (P = 0.007). Simple regression analysis showed that age, systolic blood pressure, LDL-cholesterol, the MCP-1 −2518 AG + GG polymorphism, and HbA1c level were correlated with IMT (P < 0.0001, <0.0001, 0.006, 0.007, 0.025, respectively). In multiple regression analysis, the MCP-1 −2518 AG + GG polymorphism was the third strongest independent determinant of IMT in patients with type 2 diabetes (P = 0.021), subsequent to age and systolic blood pressure.ConclusionAssessment of the MCP-1 A-2518G polymorphism would be useful in identifying the risk of developing carotid atherosclerosis in patients with type 2 diabetes.     

Association of Protein Tyrosine Phosphatase Nonreceptor 22 (PTPN22) C1858T gene polymorphism with susceptibility to autoimmune thyroid diseases: a meta-analysis

Results from studies on the association of PTPN22 C1858T polymorphism with AITD risk are conflicting, we thereby perform this meta-analysis to derive a more precise effect on this possible association. Two investigators independently searched the PubMed, Embase, Wanfang and CNKI (China National Knowledge Infrastructure) databases. A total of 11 studies with 3764 AITDs cases and 3328 controls were finally identified. Statistically significant association was observed between PTPN22 C1858T polymorphism and AITD risk based on all studies (TT vs. CC, OR=2.18, 95%CI=1.31?3.62; TC vs. CC, OR=1.50, 95%CI=1.29?1.73; TT/TC vs. CC, OR=1.41, 95%CI=1.12?1.78; TT vs. TC/CC, OR=2.00, 95%CI=1.21?3.33). The results of subgroup analysis showed that: (1) regarding ethnic diversity, the variant genotypes TT/TC of C1858T were associated with a significantly increased AITD risk in Caucasians (TT/TC vs. CC, OR=1.41, 95%CI=1.09?1.83) (2) regarding different countries, the statistically significantly association was observed in UK (TC vs. CC, OR=1.64, 95%CI=1.36?1.98; TT/TC vs. CC, OR=1.65, 95%CI=1.37?1.98) and other countries (including South Tunisia, Russia, Polish, Japanese) (TT vs. CC, OR=3.65, 95%CI=1.43?9.33; TT vs. TC/CC, OR=3.41, 95%CI=1.34?8.65). (3) regarding the subtypes of AITDs, patients with Graves' disease (GD) had a significant higher degree of C1858T polymorphism (TT vs. CC, OR=2.35, 95%CI=1.36?4.05; TC vs. CC, OR=1.46, 95%CI=1.12?1.89; TT/TC vs. CC, OR=1.54, 95%CI=1.33?1.80; TT vs. TC/CC, OR=2.16, 95%CI=1.25?3.72), while no association was observed in patients with Hashimoto's thyroiditis (HT). No publication bias was observed. Our results demonstrated that PTPN22 C1858T polymorphism was associated with AITD risk, especially in Caucasians.     

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.     

KLF6 IVS1 -27G/A polymorphism with susceptibility to gastric cancers in Korean

KLF6 is a key cell cycle regulator that is downregulated in several kinds of human cancers, including gastric cancer. The IVS1 -27G/A polymorphism of KLF6 has been investigated, which can influence susceptibility to gastric cancer and disease outcome. In order to investigate whether the IVS1 -27G/A polymorphism of KLF6 is associated with individual susceptibility to gastric cancer in Korea, the frequency of the polymorphism was examined in 264 gastric cancer patients and 299 healthy controls. Single nucleotide polymorphism (SNP) analysis was performed by amplifying intron 1 of KLF6 and sequencing the products. The frequencies of genotypes: G/G, G/A and A/A were 91.7% (242/264), 5.7% (15/264) and 2.6%, respectively, in gastric cancer cases and 91.9%, 7.0% and 1.1%, respectively, in healthy controls. Genotype frequencies in Korean population were very similar to those of Caucasian population. Interestingly, the male gastric cancer patients showed a significantly higher proportion of the G allele (Chi-Square test, P=0.005) compared to female gastric cancer patients. However, the polymorphism was statistically not associated with increased risk of gastric cancer in Korea. When stratified by histological subtype of gastric cancer, the risk was also not statistically significant. Thus, our results suggested that the IVS1 -27G/A polymorphism of KLF6 is not associated with an increased risk for gastric cancer in Korean population.     

Cyclin D1 G870A polymorphism and colorectal cancer susceptibility: a meta-analysis of 20 populations

Purpose  

Studies investigating the association between genetic polymorphism of cyclin D1 (CCND1) G870A and risk of colorectal cancer (CRC) reported conflicting results. In order to derive a more precise estimation of the relationship, a meta-analysis was performed.     

T300A polymorphism of ATG16L1 and susceptibility to inflammatory bowel diseases:A meta-analysis

AIM:To evaluate the association of the autophagy- related 16-like 1 (ATG16L1 ) T300A polymorphism (rs2241880) with predisposition to inflammatory bowel diseases (IBD) by means of meta-analysis.METHODS: Publications addressing the relationship between rs2241880/T300A polymorphism of ATG16L1 and Crohn‘s disease (CD) and ulcerative colitis (UC) were selected from the MEDLINE and EMBASE data-bases. To make direct comparisons between the data collected in these studies, the individual authors were contacted when...     

Relationship between the IL12B (rs3212227) gene polymorphism and susceptibility to multiple autoimmune diseases: A meta-analysis

Objectives: The purpose of this study was to evaluate whether a single-nucleotide polymorphism (SNP) IL12B 3^′UTR +1188A/C (rs3212227) confers susceptibility to several autoimmune diseases.

Methods: A systematic literature search was conducted to identify relevant studies. Pooled odds ratio (OR) with 95% confidence interval (CI) was used to estimate the strength of association.

Results: Twenty-five studies were included in the meta-analysis, which contained 9794 cases and 11,330 controls. Our result indicated that IL12B +1188A/C (rs3212227) polymorphism was associated with type-1 diabetes (T1D) in the dominant model (p?=?0.008), and an increased risk was found in East Asians in the dominant model (p?<?0.001). East Asians rheumatoid arthritis (RA) patients seemed to be at risk of allelic model (p?=?0.011). As to Behcet's disease (BD), there was a risk in dominant model (p?=?0.020) and positive associations of dominant model, allelic model in East Asians (p?=?0.009; p?<?0.001, respectively). But we failed to find any association between IL12B +1188A/C (rs3212227) polymorphism with Graves’ disease (GD) and ankylosing spondylitis (AS).

Conclusions: The present study suggests that the IL12B +1188A/C (rs3212227) polymorphism might be associated with genetic susceptibility to autoimmune diseases, such as T1D, RA, BD, but not GD and AS.     

TNF 308 G/A polymorphism and type 1 diabetes: A meta-analysis

We conducted a meta-analysis to examine the association between TNF 308 G/A polymorphism and risk for T1DM. Eleven reports were identified. Our study confirmed that a higher frequency of TNF 308 A allele conferred a significant risk for T1DM. Potential explanations were discussed.     

Cytotoxic T-lymphocyte antigen 4 gene +49A/G polymorphism significantly associated with susceptibility to primary biliary cirrhosis: a meta-analysis

OBJECTIVE: To evaluate comprehensively the association of cytotoxic T‐lymphocyte antigen 4 (CTLA‐4) +49A/G polymorphism with susceptibility to primary biliary cirrhosis (PBC). METHODS: PubMed was used to search for the relevant published articles. The risk of PBC association with the CTLA‐4+49A/G polymorphism was estimated for each study in a random‐effects model. Odds ratio (OR) and 95% confidence interval (CI) were estimated for each study. Risks to PBC were estimated by stratified analysis in patients with different ethnicity and antimitochondrial antibody (AMA) status, as well as histological stages. RESULTS: A total of 12 articles were included in the study. An association between PBC and CTLA‐4 G allele was found, overall OR = 1.20, 95% CI 1.03–1.41 (P = 0.02). However, stratification by ethnicity indicated a significant association between the G allele and PBC in Asians (OR = 1.36, 95% CI 1.12–1.65, P = 0.002), but not in Caucasians (OR = 1.15, 95% CI 0.95–1.39, P = 0.15). Moreover, AMA positive patients carrying G allele were more susceptible to PBC compared with AMA negative patients (OR = 1.23, 95% CI 1.06–1.43, P = 0.007; OR = 0.98, 95% CI 0.71–1.34, P = 0.88, respectively). CONCLUSIONS: Polymorphism in exon 1 of CTLA‐4 gene at position 49 may act as a candidate of susceptibility locus to PBC. However, larger studies with participants of varying ethnicity and stratified by clinical and laboratory characteristics are needed to validate our findings.