systemic lupus erythematosus ( sle ) is a chronic and progressive multisystem autoimmune connective tissue disorder , which is characterized by immune - mediated host tissue destruction . occupational exposure , chemicals , drugs , food , as well as viral and bacterial infectious agents can contribute significantly to   changes in the immune system [ 2 , 3 ] . 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 [ 47 ] . the defective function of cd4 t cells associated with abnormal stimulation of b cells causes abundant autoantibody production [ 4 , 6 ] . these autoantibodies form immune complexes with antigens on the patient 's own cells and are accumulated in the skin , synovium , lungs , renal glomeruli , and other organs and tissues . the pathogenesis of sle remains unclear , though there is much evidence demonstrating the involvement of genetic factors in the incidence of this autoimmune disease [ 913 ] . the genetic background contributing to sle development includes , in particular , genes encoding disparate proteins that control immune system pathways [ 9 , 10 , 13 ] . 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 . evidence in animal and human studies suggests a significant role of mcp-1 in the progression of glomerular and tubulointerstitial injuries and glomerulonephriti in patients with sle [ 1519 ] . 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 [ 20 , 21 ] . the mcp-1 2518 g allele , compared to the 2518 a allele , is linked with increased production of both mcp-1 transcript and protein [ 20 , 21 ] . involvement of the mcp-1 2518 a > g promoter polymorphism in sle development and its contribution to some clinical manifestations of sle remains controversial [ 2228 ] . we analysed the distribution of functional mcp-1 2518 a > g polymorphic variants in sle patients ( n = 199 ) and controls ( n = 250 ) . one hundred ninety nine ( women only ) patients fulfilling the american college of rheumatology classification criteria for sle [ 29 , 30 ] were chosen for investigation at institute of rheumatology in warsaw , poland ( table 1 ) . the protocol of the study was approved by the local ethical committee of pozna university of medical sciences . the mean age of sle patients at diagnosis was 36  12 years , and of controls , 35  11 years . 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 5-ctttcccttgtgtgtcccc-3 and 5-ttactccttttctccccaacc-3. the pcr - amplified fragments of mcp-1 that were 940  bp in length were isolated and subjected to digestion with endonuclease pvuii ( cag / ctg ) ( new england biolabs , ipswich , usa ) . the mcp-1 2518 g allele was cleaved into 650  bp and 290  bp fragments ; whereas the mcp-1 2518 a allele remained uncut . dna fragments were separated by electrophoresis on 2% agarose gel and visualized by ethidium bromide staining . the prevalence of genotypes in patients and controls was examined for deviation from hardy - weinberg equilibrium . uncorrected chi 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 . associations between clinical manifestations , production of autoantibodies , and polymorphism distribution in patients with sle were determined by fisher exact test . the mann - whitney test for nonparametric data was used to determine the statistical difference in sle disease activity index ( sledai )   between mcp-1 gg , ag , and aa genotype groups . power analysis was performed using uncorrected chi test , which is available at an online internet service : http://biostat.mc.vanderbilt.edu/twiki/bin/view/main/powersamplesize . 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 2 ) . or for sle patients with the gg genotype was 0.8629 ( 95% ci = 0.44281.682 , p = 0.6647 ) , and or of the gg   and ag   genotypes was 0.9320 ( 95% ci = 0.64211.353 , p = 0.7111 ) ( table 2 ) . the power of this study amounted to 7.0% for the gg genotype and 6.6% for the gg and ga genotypes . we also did not observe a difference in the distribution of alleles between patients and controls . or for the mcp-1 2518 g allele frequency was 0.9314 ( 95% ci = 0.69631.246 , p = 0.6320 ) . since the previous studies indicated the contribution of either mcp-1 2518 gg or ag genotypes to some clinical sle manifestations [ 22 , 23 , 28 ] , we assessed the association of these genotypes to clinical findings in our investigated group . we observed the association between the gg versus ag and aa genotypes and ag and gg versus aa genotypes with renal manifestations of sle or = 3.614 ( 1.12311.631 , p = 0.0345 ) and or = 2.297 ( 1.3014.057 , p = 0.0046 ) , respectively ( table 1 ) . however , these p - values did not remain statistically significant after bonferroni correction ( pcorr = 0.621 ; pcorr = 0.0828 , resp . ) . we observed an association between the gg versus aa genotypes with renal manifestations or = 4.923 ( 1.48316.343 , p = 0.0067 ) ( pcorr = 0.1206 ) ( table 1 ) . there was also an association of the mcp-1 ( ag and gg versus aa ) genotypes with occurrence of thrombocytopenia or = 2.618 ( 1.2805.352 , p = 0.0089 ) ( pcorr = 0.1602 ) in sle patients ( table 1 ) . we did not find a significant association between the gg genotype or g allele with the presence of anti - dsdna , anti - smith , anti - snrnp , anti - ro , anti - scl-70 , or antiphospholipid antibodies . there were also no significant differences in sledai at diagnosis between mcp-1 gg , ag , and aa genotype groups . 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 [ 3338 ] . moreover , the mcp-1 2518 g variant may also contribute to ocular behet 's disease , adult and juvenile type of rheumatoid arthritis , systemic sclerosis , and psoriasis [ 3943 ] . reports on the contribution of the mcp-1 2518 a > g polymorphism to sle incidence and clinical manifestations have been inonsistent [ 2228 , 44 , 45 ] . we did not observe differences in the distribution of the mcp-1 2518 a > g polymorphic variant between patients with sle and healthy individuals ; however this may be due to the low power of our investigation . 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 [ 2326 , 44 , 45 ] . by contrast , tucci et al . showed a significant association of the mcp-1 ag and gg genotypes to sle incidence in patients from north america moreover , brown et al . found that caucasians bearing the mcp-1 2518 g allele exhibited a significantly increased risk of developing sle . 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 . furthermore , the mcp-1 2518 g allele was associated with cutaneous vasculitis in a spanish sle group , arthritis in chinese adults with sle   and the presence of anti - dsdna and antiphospholipid antibodies in mexican patients with sle . 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 . cloned the distal regulatory region of a luciferase reporter gene , including the mcp-1 2518 a > g polymorphic variant upstream of the reporter gene . they indicated that peripheral blood mononuclear cells with either the mcp-1 ag or gg genotype demonstrated increased interleukin 1 beta - induced mcp-1 transcription compared to cells with genotype aa . moreover , fenoglio et al . also showed that alzheimer 's disease patients bearing at least one mcp-1 - 2518 g allele exhibited a significant increase of mcp-1 levels in blood plasma . 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 [ 4648 ] . this mcp-1 production by renal cells can be enhanced by the mcp-1 2518 g variant leading to the renal manifestations of sle observed in both our investigation and other studies . 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 [ 50 , 51 ] . the interaction of cd40l from activated platelets with cd40 on endothelial cells induces an inflammatory reaction in the endothelium leading to the secretion of chemokines , including mcp-1 . this may produce signals for the recruitment and extravasations of macrophages , which are able to interact with anti - platelet antibodies complexed with the platelets , which may lead to platelet destruction . our genetic investigation suggests that the mcp-1 2518 g variant can contribute to some clinical findings in patients with sle . however , to more precisely evaluate the effect of the mcp-1 2518 g variant on sle manifestations , further examination of this variant 's distribution in other sample populations is required .
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 ( n = 199 ) and controls ( n = 250 ) in poland . 
 we did not observe a significant difference in the distribution of mcp-1 2518 a > g polymorphic variants in patients with sle and healthy individuals . 
 however , we found an association between the gg versus ag and aa genotypes as well as   the ag and gg versus aa genotypes with renal manifestations of sle or = 3.614 ( 1.12311.631 , p = 0.0345 ) and or = 2.297 ( 1.3014.057 , p = 0.0046 ) , respectively . 
 we also observed that the mcp-1 ag and gg -genotypes contribute to the occurrence of thrombocytopenia in sle patients or = 2.618 ( 1.2805.352 , p = 0.0089 ) . 
 our observations indicate that either mcp-1 2518 g variant can be associated with some clinical findings in patients with sle .