Dataset Information

The rs1024611 in the CCL2 gene and risk of gynecological cancer in Asians: a meta-analysis.

ABSTRACT: The -2518A/G (rs1024611) polymorphism of the CCL2 (C-C motif chemokine ligand 2), also known as MCP-1 (monocyte chemotactic protein-1) gene, has been reported to be associated with increased gynecological cancer risk, but the results are conflicting.In this analysis, 1089 cases and 1553 controls from six publications were used to investigate the association between CCL2-2518A/G (rs1024611) polymorphism and the risk of gynecological cancer with a meta-analytic approach. Studies published on EBSCO, EMBASE, Web of Science, PubMed, SpringerLink, ScienceDirect, Weipu, and CNKI databases were identified (last update was on November 3, 2015). Six articles focused on the association between CCL2-2518A/G (rs1024611) polymorphism, and gynecological cancer risk was selected and data were extracted. The cancer type included endometrial cancer (n?=?1), breast cancer (n?=?2), ovarian cancer (n?=?2), and cervical cancer (n?=?1). All statistical analyses were performed using the STATA version 12.0 software.The meta-analysis showed that CCL2-2518A/G (rs1024611) polymorphism is associated with risk of gynecological cancer (GG vs AG?+?AA, OR?=?1.55, 95%CI?=?1.07-2.24, P?

SUBMITTER: He S

PROVIDER: S-EPMC5819160 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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The rs1024611 in the CCL2 gene and risk of gynecological cancer in Asians: a meta-analysis.

He Shuying S Zhang Xiuzhen X

World journal of surgical oncology 20180220 1

<h4>Background</h4>The -2518A/G (rs1024611) polymorphism of the CCL2 (C-C motif chemokine ligand 2), also known as MCP-1 (monocyte chemotactic protein-1) gene, has been reported to be associated with increased gynecological cancer risk, but the results are conflicting.<h4>Methods</h4>In this analysis, 1089 cases and 1553 controls from six publications were used to investigate the association between CCL2-2518A/G (rs1024611) polymorphism and the risk of gynecological cancer with a meta-analytic a ...[more]

PMID: 29458367

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Project description:CC chemokine ligand 2 (CCL2) is the most potent monocyte chemoattractant and inter-individual differences in its expression level have been associated with genetic variants mapping to the cis-regulatory regions of the gene. An A to G polymorphism in the CCL2 enhancer region at position -2578 (rs1024611; A>G), was found in most studies to be associated with higher serum CCL2 levels and increased susceptibility to a variety of diseases such as HIV-1 associated neurological disorders, tuberculosis, and atherosclerosis. However, the precise mechanism by which rs1024611influences CCL2 expression is not known. To address this knowledge gap, we tested the hypothesis that rs1024611G polymorphism is associated with allelic expression imbalance (AEI) of CCL2. We used haplotype analysis and identified a transcribed SNP in the 3'UTR (rs13900; C>T) can serve as a proxy for the rs1024611 and demonstrated that the rs1024611G allele displayed a perfect linkage disequilibrium with rs13900T allele. Allele-specific transcript quantification in lipopolysaccharide treated PBMCs obtained from heterozygous donors showed that rs13900T allele were expressed at higher levels when compared to rs13900C allele in all the donors examined suggesting that CCL2 is subjected to AEI and that that the allele containing rs1024611G is preferentially transcribed. We also found that AEI of CCL2 is a stable trait and could be detected in newly synthesized RNA. In contrast to these in vivo findings, in vitro assays with haplotype-specific reporter constructs indicated that the haplotype bearing rs1024611G had a lower or similar transcriptional activity when compared to the haplotype containing rs1024611A. This discordance between the in vivo and in vitro expression studies suggests that the CCL2 regulatory region polymorphisms may be functioning in a complex and context-dependent manner. In summary, our studies provide strong functional evidence and a rational explanation for the phenotypic effects of the CCL2 rs1024611G allele.

Project description:Introduction To a large extent, a person's susceptibility to developing periodontitis is determined by their genetic makeup. Research has shown that chemokines generated during an immune response can harm the periodontal ligaments, gingiva, and alveolar bone. Various chemokine genes located on different chromosomes contribute to periodontitis, and one such gene is C-C motif chemokine ligand 2 (CCL2), associated with the rs1024611 polymorphism, which is part of a cytokine gene cluster on the q-arm of chromosome 17. Objective Our specific objective was to investigate whether CCL2 polymorphisms could influence the relative risk of developing periodontitis. Building on these findings, we aimed to compare the frequency of a specific single nucleotide polymorphism (SNP) in the CCL2 gene between individuals with and without periodontitis. Materials and methods Fifty participants were enrolled in the study after obtaining informed consent and ethical clearance. Clinical assessments, including probing pocket depth, clinical attachment loss, and bleeding on probing, were utilized to classify individuals into two groups: a control group (Group A, n=25) and a periodontitis group (Group B, n=25). DNA extraction from collected samples involved drawing 2 ml of venous blood from the antecubital fossa and transferring it into a sterile tube with a pinch of ethylene diamine tetraacetic acid (EDTA) to prevent clotting. DNA extraction was performed and polymorphisms of CCL2 were assessed through polymerase chain reaction (PCR) and restriction enzyme digestion. Results The periodontitis group consisted of 25 patients, with an average age of 39.0±0.22 years, who met the American Academy of Periodontology's 2018 criteria for at least stage II periodontitis. The control group comprised 25 individuals with an average age of 41.3±0.49 years. Regarding the CCL2 gene polymorphism (rs1024611), there was no substantial variation in genotype frequencies between the patients and controls (p = 0.695). An agarose gel electrophoretogram, along with a standard DNA ladder, demonstrated partial amplification of the CCL2 gene spanning the polymorphism site (rs1024611). Genotypes observed were as follows: homozygous AA - 333 bp; heterozygous AG - 333 + 250 + 73 bp; homozygous GG - 250 + 73 bp. Conclusion In conclusion, there is no significant association between the CCL2 gene polymorphism rs1024611 and susceptibility to periodontitis.

Dataset Information

The rs1024611 in the CCL2 gene and risk of gynecological cancer in Asians: a meta-analysis.

Publications

The rs1024611 in the CCL2 gene and risk of gynecological cancer in Asians: a meta-analysis.

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