There is conflicting evidence on the contribution of the MCP-1 −2518 A>G (rs 1024611) polymorphism to SLE incidence and clinical manifestations.
We examined the prevalence of the MCP-1 −2518 A>G polymorphism in SLE patients (
Systemic lupus erythematosus (SLE) is a chronic and progressive multisystem autoimmune connective tissue disorder, which is characterized by immune-mediated host tissue destruction [
Immune cells from patients with SLE exhibit various defects including skewed cytokine production, a decrease in cytotoxic T cell function, and an increase in the humoral response [
The pathogenesis of SLE remains unclear, though there is much evidence demonstrating the involvement of genetic factors in the incidence of this autoimmune disease [
The monocyte chemoattractant protein 1 (MCP-1), currently also designated CCL2, belongs to the family of chemotactic cytokines. MCP-1 functions as a potent agonist for monocytes, memory T cells, and basophils [
It has been demonstrated that the MCP-1 –2518 A>G (rs 1024611) transition in the promoter region may modulate the levels of MCP-1 expression [
One hundred ninety nine (women only) patients fulfilling the American College of Rheumatology Classification criteria for SLE [
Association of the MCP-1 –2518 A>G polymorphism with clinical manifestation in patients with SLE.
Characteristic | Genotypes distribution | |||
A/A (103) | A/G (80) | G/G (16) | Odds ratio (95% CI), | |
Malar rash | 46 | 39 | 6 | |
Discoid rash | 32 | 23 | 5 | |
Photosensitivity | 47 | 38 | 7 | |
Oral ulcers | 41 | 32 | 6 | |
Arthritis | 59 | 42 | 8 | |
Serositis | 18 | 13 | 3 | |
Renal | 39 | 44 | 12 | 3.614 (1.123–11.631, |
Neurologic symptoms | 19 | 16 | 4 | |
Hematologic symptoms | 28 | 23 | 6 | |
Thrombocytopenia | 14 | 23 | 5 | 2.618 (1.280–5.352, |
Leukopenia | 21 | 16 | 3 | |
Immunologic symptoms | 51 | 43 | 7 | |
ANA | 103 | 80 | 16 |
Comparison genotype
DNA was isolated from peripheral white blood cells employing a standard salting out procedure. The presence of the MCP-1 –2518 A>G (rs 1024611) polymorphic variant was identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). PCR was carried out using primer pair
The prevalence of genotypes in patients and controls was examined for deviation from Hardy-Weinberg equilibrium. Uncorrected Chi2 test was employed to examine differences in genotypic and allelic distribution between patients and controls. Moreover, the Odds Ratio (OR) and 95% Confidence Intervals (95% CI) were calculated. A
Genotype analysis of the MCP-1 –2518 A>G polymorphism did not reveal a significant deviation form Hardy-Weinberg equilibrium in any group. We did not observe a significant difference in the prevalence of the MCP-1 –2518 A>G polymorphic variant in patients with SLE and healthy individuals (Table
Association of the MCP-1 –2518 A>G polymorphisms in SLE patients and controls.
MCP-1 –2518 A>G (rs1024611) | SLE | Controls | OR | 95%CI | |
---|---|---|---|---|---|
Genotype frequency | |||||
A/A | 103 (51.8) | 125 (50.0) | |||
A/G | 80 (40.2) | 102 (40.8) | |||
G/G | 16 (8.0) | 23 (9.2) | 0.8629 | 0.4428–1.682 | 0.6647 |
A/G+ G/G | 96 (48.2) | 125 (50.0) | 0.9320 | 0.6421–1.353 | 0.7111 |
Allele frequency | |||||
A | 286 (71.9) | 352 (70.4) | |||
G | 112 (28.1) | 148 (29.6) | 0.9314 | 0.6963–1.246 | 0.6320 |
The Odds ratio was calculated for patients
We also determined the OR for the patients’ minor allele
Since the previous studies indicated the contribution of either MCP-1 –2518 GG or AG genotypes to some clinical SLE manifestations [
Completion of the human genome project revealed the existence of approximately ten million single nucleotide polymorphisms (SNPs). However, the role of SNPs in states of either health or sickness remains under investigation [
To date, the MCP-1 –2518 A>G polymorphism has been associated with coronary artery disease, nonfamilial idiopathic dilated cardiomyopathy, carotid atherosclerosis in patients with type 2 diabetes, myocardial infarction, ischemic heart disease, and hypertension [
Reports on the contribution of the MCP-1 –2518 A>G polymorphism to SLE incidence and clinical manifestations have been inonsistent [
There have been no reports of a contribution of either the MCP-1 AG or GG genotype to SLE incidence in African American, Spanish, Korean, and Mexican cohorts [
These conflicting reports on the effect of the MCP-1 –2518 A>G polymorphism to the incidence of SLE in various populations may be due to differences in the racial heterogeneity of the examined groups. This disparity may also have resulted from each population’s exposure to distinct environmental factors, which may act in synergy with the MCP-1 –2518 A>G polymorphism to change the risk of SLE incidence among the studied populations [
We observed that the MCP-1 G/G and A/G genotypes contribute to renal manifestations of the disease. A correlation between the MCP-1 –2518 G allele and nephritis was also observed in a North American SLE cohort [
The MCP-1 –2518 A>G polymorphism is located at a relatively proximal position to the major transcriptional start site of the MCP-1 gene. Rovin et al. cloned the distal regulatory region of a luciferase reporter gene, including the MCP-1 –2518 A>G polymorphic variant upstream of the reporter gene [
It has been reported that different renal cells, including glomerular endothelial, mesangial, and tubular epithelial cells, are able to biosynthesize MCP-1 in response to immune complexes or some proinflammatory cytokines [
We also found that the MCP-1 GG and AG genotypes are associated with thrombocytopenia. An increase in serum levels of MCP-1 has previously been linked to elevated soluble CD40L in patients with autoimmune thrombocytopenic purpura [
The platelets of SLE patients are perpetually activated, and these patients exhibit an increase of soluble CD40L levels in the blood plasma [
Our genetic investigation suggests that the MCP-1 –2518 G variant can contribute to some clinical findings in patients with SLE. However
This work was supported by A grant no. 502-01-01124182-07474, Poznań University of Medical Sciences.