rs1024611
badMag 3.5This is a upstream gene variant variant in the CCL2 gene.
Key Literature Trait Associations
Cerebral infarction
A meta-analysis of studies totaling 1,272 cerebral infarction patients and 1,210 controls found that the A allele of rs1024611 significantly increased risk of cerebral infarction (A vs. G allele: OR=1.37, 95% CI: 1.18–1.60, p<0.001; dominant model GA+AA vs. GG: OR=1.33, 95% CI: 1.09–1.62, p=0.005). Cerebral infarction patients also exhibited markedly elevated MCP-1 serum levels versus controls (SMD=2.96). The opposite directionality to cardiovascular findings (where G is implicated) underscores the complexity of context-dependent MCP-1 biology and warrants cautious interpretation.
Coronary Artery Disease
The G allele at the CCL2 -2518 promoter polymorphism increases MCP-1 expression and is associated with higher coronary artery disease risk. A meta-analysis of 21 case-control studies found that GG homozygotes had 1.44-fold increased CAD risk versus AA (95% CI 1.18-1.74). The association was strongest in Caucasian populations (OR 1.49, p=0.015).
Myocardial infarction
A meta-analysis of 11 case-control studies (2,325 MI cases, 6,310 controls) found the MCP-1 -2518A>G polymorphism (rs1024611) associated with increased MI risk, with the effect concentrated in Asian populations. No significant association was detected in Caucasian populations. Ethnicity was identified as the primary source of heterogeneity across studies. The biological mechanism is plausible: the G allele drives higher CCL2/MCP-1 expression, promoting monocyte infiltration into atherosclerotic plaques, which could accelerate coronary plaque destabilization.
Type 2 diabetes mellitus
A 2023 meta-analysis (16 studies, 2,363 T2DM cases, 4,650 controls) found rs1024611 associations are strongly ancestry-dependent. In Caucasians, the G allele (GG+GA genotype) was associated with reduced T2DM risk (OR=0.79, 95% CI: 0.66–0.93, p=0.006), suggesting a protective effect. Conversely, in Asians the G allele was associated with increased diabetic nephropathy risk (OR=1.37, 95% CI: 1.11–1.71, p=0.004). No overall significant association was found when all ancestries were pooled. These findings highlight the importance of ancestry-stratified analysis for this variant.
Systemic lupus erythematosus
A meta-analysis of 16 studies (2,425 SLE cases, 2,567 controls) found no overall association between rs1024611 and SLE susceptibility. However, in Caucasian subgroup analysis, the AA genotype was significantly associated with progression to lupus nephritis (OR=0.71 for AA vs. non-AA, 95% CI: 0.54–0.93, p=0.01), indicating that A-allele homozygotes are at higher risk for renal involvement. The authors proposed AA homozygosity as a potential molecular marker for predicting SLE-to-lupus nephritis progression in Caucasian patients.
Cancer
A 2021 meta-analysis of 30 case-control studies (6,777 cancer cases, 7,840 controls) found no overall association between rs1024611 and cancer risk across all populations, but a significant association emerged in Caucasians: the GG homozygous genotype was associated with substantially elevated cancer risk (GG vs. AA: OR=1.72, 95% CI: 1.12–2.64; GG vs. AG/AA: OR=1.82, 95% CI: 1.19–2.78). A companion meta-analysis in Asian populations found the GG genotype associated with increased gynecological cancer risk (OR=1.55, 95% CI: 1.07–2.24). The cancer associations are ancestry- and cancer-type specific and should be interpreted with caution given potential publication bias in smaller candidate gene studies.
Tuberculosis
A 2015 systematic review and field synopsis of host genetic factors in respiratory infectious diseases identified CCL2 rs1024611 as a risk factor for tuberculosis susceptibility, with the A allele conferring increased risk (OR=0.79 for G allele, 95% CI: 0.72–0.88, implying OR~1.27 for A allele). Smaller individual studies have shown mixed results, with a multi-ethnic study across West Africa, the US, and Argentina finding inconsistent effects across populations. The MCP-1 pathway's role in granuloma formation and mycobacterial containment provides a plausible mechanistic basis for this association.
▶ClinVar annotation
CCL2-related disorder; Coronary artery disease, development of, in HIV; Coronary artery disease, modifier of; Mycobacterium tuberculosis, susceptibility to; Spina bifida, susceptibility to
View on ClinVar →▶Research that mentions this SNP (9)
▶Association of MCP‐1 promotor polymorphism with disease severity of Crimean‐Congo hemorrhagic feverAssociationN=309Binnur Bagci et al.(2020)· Journal of Medical Virology
This case-control association study examined the MCP-1 promoter -2518 A/G SNP (rs1024611) in 128 Crimean-Congo hemorrhagic fever (CCHF) patients and 181 healthy controls. The AA genotype and A allele were associated with increased disease severity (OR=2.41, p=0.02 for AA vs AG+GG), while the AG genotype showed protective effects against severe disease (OR=2.58, p=0.013). No significant associations were found between genotype and fatal outcomes.
▶Genetic polymorphism patterns suggest a genetic driven inflammatory response as pathogenesis in appendicitisAssociationN=343Jan Dimberg et al.(2020)· International Journal of Colorectal Disease
This case-control study analyzes 28 SNPs in 26 inflammatory response genes in 343 patients (100 with appendicitis, 243 controls) using TaqMan genotyping. Significant associations were found for IL-13 rs1800925 (OR=6.02, 95% CI 1.52-23.78), IL-17 rs2275913 (OR=2.38, 95% CI 1.24-4.57), and CCL22 rs223888 (OR=0.12, 95% CI 0.02-0.90), suggesting a genetic-driven inflammatory response as a pathogenic mechanism in appendicitis.
▶The Frequency of Monocyte Chemoattractant Protein-1 Gene Polymorphism in Obstructive Sleep Apnea SyndromeAssociationN=301Buğra Kerget et al.(2019)· Lung
This case-control study of 301 subjects (201 OSAS patients and 100 controls) evaluated the association between MCP1 gene polymorphisms and coronary artery disease (CAD) in obstructive sleep apnea syndrome patients. The homozygous GG genotype of rs1024611 was significantly more prevalent in OSAS+CAD patients (70.3%) compared to OSAS-only (48.2%) and control groups (51%; p<0.001). rs1024610 showed no significant associations. The findings suggest MCP1 rs1024611 homozygous mutation is an independent risk marker for CAD development in OSAS patients.
▶NOTCH4 is a possible novel susceptibility gene for dilated cardiomyopathy in the Chinese population: A case‐control studyAssociationN=821Xiaoqing Shi et al.(2018)· Journal of Clinical Laboratory Analysis
A case-control study of 273 DCM patients and 548 controls in the Chinese Han population examined seven genetic variants associated with cardiac neonatal lupus. The study found that the T allele of rs3134942 in NOTCH4 increased DCM risk by 61% (OR=1.61, 95% CI: 1.15-2.27, P=6.57×10⁻³) in additive and dominant models. Additionally, rs2472299 in CYP1A2 was associated with reduced DCM risk in the dominant model (OR=0.72, P=4.24×10⁻²) and correlated with smoking status in patients.
▶The CC chemokine ligand 2 (CCL2) polymorphism −2518A/G is associated with gout in the Chinese Han male populationAssociationN=2,143Ruixia Sun et al.(2015)· Rheumatology International
A case-control study of 1,109 gout patients and 1,034 controls in a Chinese Han male population examining the CCL2 -2518A/G polymorphism (rs1024611). The G allele was significantly associated with increased gout susceptibility (OR 1.182, 95% CI 1.047-1.335, p=0.007), with genotypic distribution differences between cases and controls (adjusted p=0.021).
▶Genome‐wide association study of neurocognitive impairment and dementia in HIV‐infected adultsAssociationN=1,287Andrew J. Levine et al.(2012)· American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
First genome-wide association study (GWAS) of HIV-associated neurocognitive disorders (HAND) in 1287 HIV-infected adults from the Multicenter AIDS Cohort Study. The study examined neurocognitive decline in processing speed and executive functioning over time, as well as prevalence of HIV-associated dementia and neurocognitive impairment across ~2.5 million SNPs. No genome-wide significant associations were identified with any neurocognitive phenotype examined. Previously reported candidate gene associations with HAND (including rs1130371 in MIP1α, rs1800629 in TNFα, rs1801157 in SDF-1, and rs2839619 in PREP1) were not validated in this study.
▶Association of IL23R, TNFRSF1A, and HLA-DRB1*0103 allele variants with inflammatory bowel disease phenotypes in the Finnish populationAssociationN=7,457Maarit Lappalainen et al.(2008)· Inflammatory Bowel Diseases
PhD thesis describing comprehensive genome-wide association studies of acute anterior uveitis (AAU) in European (2,752 cases, 3,836 controls) and East Asian (821 cases, 4,898 controls) populations. European descent GWAS identified HLA-B at genome-wide significance plus 11 suggestive loci (ERAP1, NOS2, MERTK). East Asian GWAS identified HLA-B and ERAP1 at genome-wide significance plus 12 suggestive loci (GPR68, RHBDD2). Mendelian randomization confirmed ERAP1 as functionally relevant and showed genetically predicted CRP levels positively associated with AAU risk.
▶The –786C/T single‐nucleotide polymorphism in the promoter of the gene for endothelial nitric oxide synthase: Insensitivity to physiologic stimuli as a risk factor for rheumatoid arthritisAssociationN=219Inga Melchers et al.(2006)· Arthritis & Rheumatism
This journal issue contains multiple genetic association studies on rheumatoid arthritis (RA). A key REMARCA study (146 aCCP+ RA patients vs 314 controls) identified polymorphisms in CTLA4 (rs231775 +49A/G), IL10 (rs1800872 -592A/C), and IL6R (rs8192284 +358A/C) associated with high inflammatory disease activity, with CTLA4 and IL10 minor alleles showing increased risk (OR=1.4, p=0.02 and OR=1.9, p<0.0001 respectively) and IL6R minor allele being protective (OR=0.7, p=0.03). A separate study analyzed NOS3, PPARG, PPARGC1A, PPARGC1B and PAI1 polymorphisms in 73 RA patients for cardiovascular risk.
▶Association between the PTPN22 gene and rheumatoid arthritis and juvenile idiopathic arthritis in a UK population: Further support that PTPN22 is an autoimmunity geneAssociationN=436Anne Hinks et al.(2005)· Arthritis & Rheumatism
Candidate gene association study of 122 early rheumatoid arthritis (RA) patients and 314 healthy controls found that PTPN22 rs2476601 (OR=1.5, 95% CI 1.0-2.3, p=0.05) and TNFAIP3 rs675520 (OR=1.7) polymorphisms were significantly associated with RA risk. Anti-cyclic citrullinated peptide (ACPA) antibody production was associated with PTPN22, TNFAIP3, CTLA4, and TNF-α polymorphisms in a dose-dependent manner.
Gene information from NCBI Gene. Variant classifications from ClinVar.
Community Wiki
No community notes yet for this variant. Sign in to start one.
Comments
Sign in to join the discussion.
Loading comments…