Association Of Monocyte Chemoattractant Protein-1 Research Articles

Association of Monocyte Chemoattractant Protein-1 (MCP-1) 2518 A/G Polymorphism with Obesity in Korean Type 2 Diabetes Mellitus.

Monocyte chemoattractant protein-1 (MCP-1) is a member of the CC chemokine family, and the MCP-1 2518 A/G gene polymorphism is reported to be correlated with chronic inflammatory diseases, including insulin resistance and metabolic syndrome. However, few studies have investigated the association between MCP-1 gene polymorphisms and obesity in patients with type 2 diabetes mellitus (T2DM). We conducted a retrospective case-control study and evaluated the association between the MCP-1 2518 A/G polymorphism and obesity in Korean patients with T2DM. This single-center, retrospective, case-control study enrolled 526 Korean patients with T2DM. Obesity was defined using the body mass index (BMI) with a cutoff level of 25 kg/m2. Polymerase chain reaction-restriction fragment length polymorphism was used to analyze MCP-1 2518 A/G polymorphism; the genotypes was presented as GG, AG, or AA. We compared the MCP-1 2518 A/G polymorphism with the prevalence of diabetic complications, as well as clinical and biochemical characteristics. The obese group had a higher number of females and higher C-peptide, insulin, triglycerides, aspartate transaminase (AST), and alanine transaminase (ALT) levels. The obese group also had a higher prevalence of cardiovascular disease than the non-obese group. The obese group had a higher frequency of the MCP-1 2518 AA genotype and the A allele than the non-obese group. The results of multiple logistic regression analysis showed that the non-G allele of MCP-1 was significantly associated with obesity (odds ratio (OR), 1.888; P=0.016). This study demonstrates that the MCP-1 2518 A/G polymorphism is associated with obesity in Korean patients with T2DM. Further studies involving various ethnic groups are required to validate our results.

Unravelling the Influence of Demographic and Lifestyle Factors on Monocyte Chemoattractant Protein-1 in Diabetic Retinopathy Patients

Objectives: To determine the association of Monocyte chemoattractant protein-1 (MCP-1) level with Age, blood glucose level, Exercise, Gender and Smoking in diabetic retinopathy patients. Study Design and settings: A case-control study was carried in the physiology department at the Jinnah Postgraduate Medical Centre in Karachi From April 2019 to October 2020. Methodology: One hundred people were divided into four groups which were; Group D (n=25) were healthy normal individuals; Group C (n=25) diabetic patient's with moderate retinopathy; Group B (n=25) diabetic patient's with mild retinopathy while Group A (n=25) diabetic patients with no retinopathy. Every participant was checked for blood sugar level, retinoscopy through slit lamp examination and serum MCP-1 level. The association was made between diabetic retinopathy, MCP-1 protein levels, age, gender, smoking and exercise. Results: MCP-1 levels are significantly greater in diabetic males with moderate retinopathy compared to diabetic females with moderate retinopathy (p-value 0.042). Similarly, smoking is associated with the elevation of MCP-1 levels in diabetic patients with moderate retinopathy (p-value 0.05). Exercise has no significant effect on MCP-1 levels in all groups. An increase in age, HbA1C, fasting and random blood glucose levels were significantly correlated with MCP-1 levels ( pvalue 0.000) Conclusion: It is concluded from the study that an advance in age and an increase in blood glucose level are associated with an increased level of MCP-1 protein. Moreover, Male gender and smoking are also associated with enhanced MCP- 1 levels in diabetic patients with moderate retinopathy.

Ethnic differences in urinary monocyte chemoattractant protein-1 and heparanase-1 levels in individuals with type 2 diabetes: the HELIUS study

IntroductionWe aimed to investigate ethnic differences in two urinary inflammatory markers in participants with type 2 diabetes mellitus (T2DM).Research design and methodsWe included 55 Dutch, 127 South-Asian Surinamese, 92 African...

Association of Monocyte Chemoattractant Protein-1 with Death and Atherosclerotic Events in Chronic Kidney Disease

Background: Monocyte chemoattractant protein-1 ­(MCP-1), a marker of inflammation and monocyte recruitment to atherosclerotic plaques, is associated with cardiovascular (CV) outcomes in patients with acute coronary syndrome. Although plasma levels are elevated in chronic kidney disease (CKD), associations with reduced kidney function or outcomes in CKD have not been explored. Methods: In this population-based, probability-sampled, longitudinal cohort of 3,257 participants, including 286 (8.8%) patients with CKD, we studied the association of plasma MCP-1 with estimated glomerular filtration rate (eGFR), albuminuria, death, and intermediate and hard CV outcomes in CKD and non-CKD individuals. Cox proportional hazards regression assessed associations of baseline MCP-1 with all-cause death and atherosclerotic events. Results: MCP-1 was higher in CKD than non-CKD participants (p < 0.001), and negatively associated with eGFR (r = –0.23, p < 0.0001) but not albuminuria in CKD. MCP-1 was associated with pulse wave velocity and coronary artery calcification in non-CKD but not CKD individuals. At 13.5 years, there were 230 (7.7%) deaths and 168 (6.4%) atherosclerotic events in the non-CKD vs. 97 (34.0%) deaths and 62 (27.9%) events in the CKD group (p < 0.001 for each). MCP-1 was associated with death (hazards ratio [HR] 2.0 [1.4–2.9] per log-unit increase) and atherosclerotic events (1.7 [1.0–2.9]) in CKD individuals. The HR for death in CKD remained significant (1.6 [1.1–2.3]) after adjusting for CV risk factors. Conclusions: Although plasma MCP-1 increased with decreased eGFR, it remained an independent risk factor for death in CKD. MCP-1 did not correlate with intermediate CV outcomes, implicating pathways other than atherosclerosis in the association of MCP-1 with death in CKD.

Association of monocyte chemoattractant protein-1 2518G/A gene polymorphism with diabetic nephropathy risk

Results from the published studies on the association between monocyte chemoattractant protein-1 (MCP-1) −2518 A/G gene polymorphism and diabetic nephropathy (DN) risk are still conflicting. This meta-analysis was performed to evaluate the relationship between MCP-1 A/G gene polymorphism and DN risk and to explore whether MCP-1 A allele, AA genotype or GG genotype could become a predictive marker for DN risk. Association studies were identified from the databases of PubMed, Embase, Cochrane Library and CBM-disc (China Biological Medicine Database) as of 1 March 2014, and eligible investigations were synthesized using meta-analysis method. Four studies were identified for the analysis of association between MCP-1 A/G gene polymorphism and DN risk, and all the included studies were form Asian population. The association between MCP-1 A/G gene polymorphism and DN susceptibility was not found (A allele: OR = 1.19; 95% CI: 0.97–1.45; p = 0.10; AA genotype: OR = 1.27; 95% CI: 0.95–1.70; p = 0.11; GG genotype: OR = 0.77; 95% CI: 0.57–1.05; p = 0.10). In the sensitive analysis, according to the control source from hospital, we found that AA genotype was associated with the DN risk (OR = 1.45; 95% CI: 1.05–2.00; p = 0.02). However, other associations were not found in the sensitive analysis according to the control source from hospital or population. Our results indicate that AA homozygous might be a significant genetic molecular marker to predict the diabetes mellitus patients developing into DN. However, more investigations are required to further clarify this association.

Association of monocyte chemoattractant protein-1 (MCP-1)2518A/G polymorphism with proliferative diabetic retinopathy in northern Chinese type 2 diabetes.

The pathogenesis of proliferative diabetic retinopathy (PDR) remains poorly understood. Recent studies have implicated that monocyte chemoattractant protein-1 (MCP-1) is associated with diabetic microvascular or macrovascular complications. However, the relationship between single nucleotide polymorphism(SNP)c.2518A/G -rs1024611 in the MCP-1 gene with diabetic retinopathy remains controversial. In the present study, we evaluated the association of SNP in the MCP-1 gene with diabetic retinopathy (DR) and diabetic macular edema (DME) in a Chinese population from Northern China with type 2 diabetes. We conducted a case-control study, which enrolled 1,043 subjects with type 2 diabetes (528 with DR, including 277PDR; 515 without DR), and SNP genotyping of c.2518A/G in the MCP-1 gene was performed using the polymerase chain reaction. Genomic DNA was isolated from 3 ml samples of whole blood using a modified conventional DNA extraction method. The genotype and allele frequencies of 2518A/G were studied by using an automated DNA sequencer (ABI PRISM 3730 DNA Sequencer). The demographic and clinical characteristics did not differ among genotype subgroups. The MCP-1(-2518) GG genotype was significantly associated with DR susceptibility with OR of 1.481 (95 % CI, 1.019-2.153) (P = 0.046). There were no significant differences in the MCP-1(-2518) G allele frequencies in DR compared to non-diabetic retinopathy (DNR) (P > 0.05, OR = 0.841, 95 % CI, 0.705-1.002). The MCP-1(-2518) GG genotype was significantly associated with high-risk PDR susceptibility with OR of 2.656 (95 % CI, 1.222-5.775) (P = 0.014). The MCP-1(-2518) G allele was significantly increased in high-risk PDR patients (P = 0.020, OR = 1.481, 95 % CI, 1.070-2.051) compared with A allele. Genotype and allele frequencies of various DME of the DR patients were compared, but there were no significant associations established (P > 0.05). It is likely that the MCP-1 c.2518G/G genotype is a susceptibility gene for DR in Chinese type 2 diabetic patients, especially the high-risk PDR. There is no association with DME and c.2518G/G.

260 : Association of polymorphic variation of MCP-1 (-2518 A/G) SNP with clinical symptoms in systemic lupus erythematosus patients from western India

Systemic Lupus Erythematosus (SLE) is a clinically heterogeneous chronic, inflammatory autoimmune disorder that affects multiple organs. The exact etiology of the disease is not clearly understood. Various polymorphisms in genes of inflammatory mediators influence development of the disease. In this study, we have tried to see the association of Monocyte Chemoattractant Protein-1 (MCP-1) −2518 A/G Single Nucleotide Polymorphism (SNP) with clinical symptoms in Indian SLE cohort. The case control study conducted on 173 clinically diagnosed Indian SLE patients and 163 ethnically matched healthy controls. The disease severity was categorised into mild, moderate and severe based on SLEDAI score. The SLEDAI score varied from 3 to 41. Genotyping of MCP-1 (−2518 A/G) polymorphism was performed using a (PCR-RFLP) method. Arthritis and Malar rash were the clinical manifestations predominantly seen among our SLE patients. We did not report a statistically significant difference (p > 0.05) in the distribution of MCP-1 −2518 A/G polymorphic variants among SLE patients (29.77%) as compared to healthy individuals (36.8%). When we tried to evaluate its effect on clinical manifestations, we found statistically significant association of MCP-1 (−2518A/G) polymorphisms with the renal disorder (p

Association of MCP-1 -2518A/G and -362G/C variants and tuberculosis susceptibility: A meta-analysis

A number of studies have found that the -2518A/G and -362G/C polymorphisms in the monocyte chemoattractant protein-1 (MCP-1) gene are implicated in the susceptibility to tuberculosis. However, the results are inconsistent. To investigate the relationship between -2518A/G and -362G/C polymorphisms in MCP-1 gene and the susceptibility of tuberculosis, a systematic literature search for relevant articles published up to January, 2013 was conducted in the databases of PubMed, Elsevier, Web of Science, Wanfang and CNKI. A total number of twenty-two case-control studies that included 9365 cases and 10149 controls on two single-nucleotide polymorphisms (SNPs): -2518A/G and -362G/C, were identified. The results indicated that the G allele of -2518A/G polymorphism was associated with increased risk of tuberculosis (GG vs. AA+AG: OR 1.455, 95% CI 1.092–1.937, P = 0.01). In the subgroup analysis by ethnicity, significant elevated risks were found in Asians and Americans, but not in Africans. The C allele of -362G/C polymorphism was associated with resistance to tuberculosis (CC vs. GG+GC: OR 0.837, 95% CI 0.772–0.987, P = 0.03). This meta-analysis suggests that the G allele of -2518A/G polymorphism is a risk factor for tuberculosis in Asians and Americans, while not in Africans. It further indicates that C allele of -362G/C polymorphism is a protective factor for tuberculosis.

MCP-1 binds to oxidized LDL and is carried by lipoprotein(a) in human plasma

Lipoprotein oxidation plays an important role in pathogenesis of atherosclerosis. Oxidized low density lipoprotein (OxLDL) induces profound inflammatory responses in vascular cells, such as production of monocyte chemoattractant protein-1 (MCP-1) [chemokine (C-C motif) ligand 2], a key chemokine in the initiation and progression of vascular inflammation. Here we demonstrate that OxLDL also binds MCP-1 and that the OxLDL-bound MCP-1 retains its ability to recruit monocytes. A human MCP-1 mutant in which basic amino acids Arg-18 and Lys-19 were replaced with Ala did not bind to OxLDL. The MCP-1 binding to OxLDL was inhibited by the monoclonal antibody E06, which binds oxidized phospholipids (OxPLs) in OxLDL. Because OxPLs are carried by lipoprotein(a) [Lp(a)] in human plasma, we tested to determine whether Lp(a) binds MCP-1. Recombinant wild-type but not mutant MCP-1 added to human plasma bound to Lp(a), and its binding was inhibited by E06. Lp(a) captured from human plasma contained MCP-1 and the Lp(a)-associated endogenous MCP-1 induced monocyte migration. These results demonstrate that OxLDL and Lp(a) bind MCP-1 in vitro and in vivo and that OxPLs are major determinants of the MCP-1 binding. The association of MCP-1 with OxLDL and Lp(a) may play a role in modulating monocyte trafficking during atherogenesis.

Association of Monocyte Chemoattractant Protein-1 (MCP-1) 2518A/G Polymorphism with Proliferative Diabetic Retinopathy in Korean Type 2 Diabetes

PurposeMonocyte chemoattractant protein-1 (MCP-1) is a chemokine that can increase adhesion molecule expression on monocytes and produce superoxide anions. Hyperglycemia induces MCP-1 production in vascular endothelial cells and retinal pigmented epithelial cells, and has been implicated as a causal factor in the facilitation of vascular complications in diabetes. In the present study, we evaluated the association of a single nucleotide polymorphism (SNP) in the MCP-1 gene with proliferative diabetic retinopathy (PDR) in a Korean population with type 2 diabetes.Materials and MethodsWe conducted a case-control study, which enrolled 590 subjects with type 2 diabetes, and SNP genotyping of c.2518A/G in the MCP-1 gene was performed using polymerase chain reaction followed by digestion with PvuII restriction enzyme.ResultsThe prevalence of c.2518A/G polymorphism in diabetic patients was 13.2% (A/A), 47.1% (A/G) and 39.7% (G/G). In patients with diabetic retinopathy, the prevalence of PDR was significantly higher (p=0.009) in diabetic subjects with the c.2518A/A genotype (35.9%; n=78) compared to those with either the A/G or G/G genotype (22.3%, n=512). The prevalence of any other micro and macro-complications, including nephropathy and cerebrovascular events, were not different according to the c.2518A/G genotype.ConclusionOur new genetic findings suggest that the c.2518A/A genotype in MCP-1 could be used as a susceptibility gene to predispose Koreans exhibiting type 2 diabetes for the development of PDR.

Association of monocyte chemoattractant protein-1 −2518A>G polymorphism with occurrence, severity, and outcome in ischemic stroke

Monocyte chemoattractant protein-1 (MCP-1) is implicated in promoting atherosclerotic diseases, including stroke. Therefore, several studies have investigated the association between variants of the MCP-1 gene and risk of atherosclerotic diseases. We sought to determine the occurrence of MCP-1 -2518A>G polymorphism in patients with ischemic stroke (IS), and studied its association with the severity of disease and functional outcome after an acute IS. One hundred and forty-five consecutive patients with first ever IS and 145 age- and sex-matched control subjects were recruited. Stroke severity and functional outcome were assessed on admission and at one month post-stroke, respectively. Genotyping for the MCP-1 -2518A>G polymorphism was performed by a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). No significant difference in the frequency of MCP-1 -2518A>G genotypes between IS patients and controls was found, with OR = 0.69 (95 % CI 0.46-1.04, P = 0.08). Moreover, carriage of the G allele was not associated with stroke severity (Scandinavian stroke scale score 33.1 vs. 32.5, respectively, P = 0.71), or poor outcome at 1 month post-stroke (63.9 vs. 59.7 %, respectively, P = 0.61). In conclusion, we were unable to demonstrate a significant association of the MCP-1 -2518A>G gene polymorphism with IS occurrence, severity or functional outcome in a Caucasian population. However, larger studies are necessary to fully elucidate the role of this polymorphism in IS.

The role of chemokine and chemokine receptor gene variants on the susceptibility and clinicopathological characteristics of bladder cancer

The gene variants of the chemokine and chemokine receptor genes associated with inflammation may be involved in cancer initiation and progression. The aim of this study was to explore the possible association of monocyte chemoattractant protein-1 (MCP-1) A2518G, stromal cell derived factor 1 (SDF-1) 3′A and chemokine receptors CCR2A V64I, CCR5 Δ32, CCR5 59029 and CXCR4 gene polymorphisms with the risk and clinicopathological characteristics of bladder cancer (BC) in a Turkish population.The genotyping was done by PCR and PCR-Restriction Fragment Length Polymorphism (RFLP) methods in 142 histologically confirmed BC patients and 197 controls.The SDF-1 3′AA genotype conferred significantly increased susceptibility to BC. The carriers with AA genotype or at least one A allele of CCR2 had an increased risk of developing BC. CCR5 wt/Δ32 genotype and CCR5 Δ32 allele were also observed to be involved in the susceptibility to BC. Additionally, the combination of CCR2 V64I and CCR5 Δ32 (i.e., GG-wt/Δ32) was found to be associated with BC risk. With respect to the stage of BC, the AA genotype of SDF-1 and at least one T allele of CXCR4 were significantly associated with high T stage as compared to GG genotype of SDF-1 and CC genotype of CXCR4. Furthermore, BC patients with AA genotype or at least one A allele of CCR2 had an increased risk of high grade and stage tumors as compared to those with GG genotype.Our results suggest that the genetic variants of SDF-1 3′A, CCR2A V64I and CCR5 Δ32 gene polymorphisms may modify the BC risk. Furthermore, SDF-1 3′A, CCR2A V64I and CXCR4 gene polymorphisms may contribute to the muscle invasive BC in a Turkish population.

Meta-analysis of MCP-1 promoter −2518 A/G polymorphism and SLE susceptibility

The aim of this meta-analysis was to summarize results on the association of monocyte chemoattractant protein-1(MCP-1) promoter -2518 A/G polymorphism with systemic lupus erythematosus (SLE) susceptibility. We searches all the publications about the association between MCP-1 promoter -2518 A/G polymorphism and SLE from Pubmed, Elsevier Science Direct, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure. The meta-analysis was performed for genotypes AA verse GG, AA+AG verse GG, AA verse AG+GG, and A allele verse G allele in a fixed/random effect model. A total of 14 studies (2,333 cases and 2,391 controls) were included in the meta-analysis. When all groups were pooled, we had not observed significant association between A allele and G allele (OR = 0.94, 95 %CI = 0.79-1.12, P = 0.50). When analysis were restricted to more ethnically homogeneous populations, the similar results were found in European population and Asian population (OR = 1.05, 95 %CI = 0.75-1.46, P = 0.80; OR = 1.00, 95 %CI = 0.86-1.17, P = 0.99). However, we had not detected a significant association between MCP-1 promoter -2518 A/G polymorphism and SLE when examining the genotypes AA verse GG, AA+AG verse GG, AA verse AG+GG. The meta-analysis did not demonstrate the association between MCP-1 promoter -2518 A/G polymorphism and SLE.

No association of monocyte chemoattractant protein-1 −2518 A/G polymorphism with the risk of primary glomerulonephritis in the Polish population

Various studies have indicated that chemokines such as monocyte chemotactic protein-1 (MCP-1) play an important role in the pathogenesis of primary glomerulonephritis (GN) and other glomerular diseases. Moreover, patients with primary GN display aberrant galactosylation of the O-linked carbohydrate moieties of IgA. Therefore, we analysed the distribution of the functional MCP-1 -2518 A>G (rs 1024611) and 1 beta 1,3-galactosyltransferase (C1GalT1) 1365 A>G (rs1047763) polymorphic variants in patients with primary GN (n=144) and controls (n=437) in a sample of the Polish population. We did not find a significant difference in the prevalence of the MCP-1 -2518 A>G and C1GalT1 1365 A>G polymorphisms in patients with primary GN and healthy individuals. Odds Ratio (OR) for GN patients with the MCP-1 -2518 GG genotype was 0.869 (95% CI=0.410-1.840, P=0.7130), and OR of the -2518 GG and -2518AG genotypes was 1.004 (95% CI=0.689-1.464, P=0.9836). OR for C1GalT1 1365AA genotype was 0.484 (95% CI=0.181-1.293, P=0.1402) and OR of the 1365AA and 1365AG genotypes was 0.839 (95% CI=0.573-1.228, P=0.3651). We also did not observe a difference in the distribution of alleles between patients and controls. The MCP-1 -2518 G allelic OR was 0.976 (95% CI=0.725-1.314, P=0.8744). The OR for the C1GalT1 1365A allele was 0.816 (95% CI=0.596-1.118, P=0.205). Moreover, there was no significant association between the MCP-1 -2518 A>G and C1GalT1 1365 A>G genotypes with different morphological types of primary GN or clinical manifestations. Our observations indicate that the MCP-1 -2518 A>G and C1GalT1 1365 A>G polymorphisms might not be a risk factor in the incidence of primary GN in the Polish population.

Variation of serum monocyte chemoattractant protein-1 in patients with diabetes and metabolic syndrome

This study investigated the variation of serum monocyte chemoattractant protein-1 (MCP-1) in patients with both diabetes mellitus (DM) and metabolic syndrome (MS). Based on the International Diabetes Federation (IDF) diagnostic criteria, 93 patients enrolled in this study were divided into four groups: normal control (NC), simple DM, simple MS, and DM plus MS (DM-MS) groups. The main measures included height, weight, waist circumference (WC), hip circumference, blood pressure, fasting blood glucose, insulin resistance index (HOMA-IR), serum triglyceride (TG), HDL-ch, LDL-ch, and MCP-1. The results showed that the serum levels of MCP-1 in the DM-MS group were significantly increased as compared with those in the DM and MS groups (P<0.05), and the increase in the MCP-1 level in the DM group was much higher than in the MS group (P<0.05). The DM-MS group had the highest HOMA-IR levels, followed by MS, DM and NC groups (P<0.05). Correlation tests showed that the association of MCP-1 with age, HDL-ch, or LDL-ch was insignificant, whereas that of MCP-1 with body mass index (BMI), waist hip rate (WHR), WC, systolic blood pressure (SBP), diastolic blood pressure (DBP), TG, and HOMA-IR was significantly positive. It was concluded that circulating MCP-1 was substantially increased in patients with both DM and MS as compared with that in the patients with DM or MS alone, and the central obese state may contribute to a more vicious proinflammatory condition and insulin resistance in patients with diabetes.

Increased monocyte chemoattractant protein-1 levels indicating early vascular damage in lean young PCOS patients

Serum levels of monocyte chemoattractant protein-1 and C-reactive protein levels, as early signs of vascular damage and cardiovascular disease, were increased in young, lean patients with polycystic ovary syndrome. Serum monocyte chemoattractant protein-1 levels were positively correlated with serum LH, T, and C-reactive protein levels.

Association of Monocyte Chemoattractant Protein-1 −2518 Polymorphism With Metabolic Syndrome in a South Indian Cohort

Previous reports have indicated an association of monocyte chemoattractant protein-1 (MCP-1) with risk factors for atherosclerosis and coronary artery disease (CAD). Because some of these risk factors form components of metabolic syndrome, in the present study, we investigated the association of an important promoter region polymorphism of MCP-1, A-2518G, and its serum levels with metabolic syndrome in a South Indian cohort. The study comprised of 126 healthy subjects aged 30-59 years from South India. Subjects were classified on the basis of presence or absence of metabolic syndrome and metabolic syndrome components as per the International Diabetes Federation definition. MCP-1 genotyping was done by polymerase chain reaction restriction fragment-length polymorphism, and serum levels were estimated by enzyme-linked immunosorbent assay. The MCP-1 -2518G allele frequency in the study population was 32.9% and the mean MCP-1 serum levels were 523 +/- 272.3 pg/mL. Subjects with metabolic syndrome showed an increased presence of the MCP-1 -2518G allele in comparison to those without metabolic syndrome (odds ratio [OR] = 5.03, P = 0.02). The association was related to a higher proportion of this allele in subjects with increased waist circumference (OR = 3.78, P = 0.05). The MCP-1 -2518G allele may be contributing to atherosclerosis and CAD by conferring an increased risk to metabolic syndrome and/or obesity.

Association of monocyte chemoattractant protein-1 and the clinical characteristics of polycystic ovary syndrome: analysis of 65 cases

To investigate the association of monocyte chemoattractant protein-1 (MCP-1) and the clinical characteristics of polycystic ovary syndrome: (PCOS). Fasting peripheral venous blood samples were collected on the 2nd or 3rd day of the menstrual cycle or when there was no dominant follicle shown by ultrasonography after amenorrhea from 65 POCS patients, aged 30 +/- 3, 27 being attributed to the obese group according the body mass index (BMI) and 38 to the non-obese group, and 40 patients with infertility, aged 31 +/- 3, as controls, subdivided into obese and non-obese subgroups (both n = 20), and then the samples of serum. Were obtained. The level of MCP-1 was examined by ELISA. The levels of prolactin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, and testosterone (T) were assayed with chemoluminescence methods, and the level of androstenedione was detected by radioimmunoassay. The level of serum insulin was detected by chemoluminescence method and the serum glucose (SG) was detected by oxidase enzymic method. Insulin sensitivity index (ISI) and homeostasis model assessment insulin resistance (HOMA-IR) were calculated. (1) The levels of serum LH, T, and LH/FSH of the obese and non-obese POCS subgroups were all significantly higher than the corresponding obese and non-obese control subgroups (all P < 0.05). (2) The level of MCP-1 of the non-obese PCOS subgroup was (98 +/- 67) ng/ml, significantly higher than that of the non-obese controls [(58 +/- 41 mg/L, P < 0.05)]. (3) Pearson correlation showed that serum PCP-1 was significantly positively correlated with BMI (r = 0.339, P = 0.000). LH (r = 0.224, P = 0.024)), and HOMA-IR (r = 0.239, P = 0.016), and significantly negatively correlated with ISI (r = -0.250, P = 0.0006). (3) Multiple regression analysis showed that BMI and LH were the principal factors influencing the level of MCP-1 in the POCS patients. The serum level of MCP-1 is associated with the LH level in POCS patients. POCS may a chronic inflammatory disease. MCP-1 is likely to participate in obesity, hyperinsulinemia, and insulin resistance in POCS.

Association of monocyte chemoattractant protein-1 with renal tubular damage in diabetic nephropathy

Monocyte chemoattractant protein-1 (MCP-1), is a chemokine that mediates renal interstitial inflammation, tubular atrophy, and interstitial fibrosis by recruiting monocytes/macrophages into renal tubulointerstitium. Recent studies have demonstrated that protein overload in renal tubular cells up-regulates MCP-1 gene and its protein expression. Therefore, we hypothesized that increased expression of MCP-1 in renal tubuli, probably triggered by an increase in the leakage of plasma protein from glomerular capillary to tubular fluid, may contribute to renal tubular damage and accelerate the progression of diabetic nephropathy. To test this hypothesis, we examined urinary excretion levels of MCP-1 and N-acetylglucosaminidase (NAG), a sensitive marker of renal tubular damage, in Japanese Type II diabetic patients with normoalbuminuria ( n=29), microalbuminuria ( n=25), and macroalbuminuria ( n=18). The median urinary excretion level of MCP-1 in patients with macroalbuminuria (394.4 ng/g creatinine) was significantly elevated compared to the levels in patients with normoalbuminuria and microalbuminuria (159.6 and 193.9 ng/g creatinine, respectively). Furthermore, the urinary MCP-1 excretion level was positively correlated with urinary excretion levels of albumin ( r=.816, P<.001) and NAG ( r=.569, P<.001) in all subjects. These results suggest that MCP-1 is produced in renal tubular cells and released into urine in proportion to the degree of proteinuria (albuminuria), and that increased MCP-1 expression in renal tubuli contributes to renal tubular damage. Therefore, we conclude that heavy proteinuria itself may accelerate the progression of diabetic nephropathy by increasing the MCP-1 expression in renal tubuli.