CCR2 V64I Research Articles

Association of polymorphisms in the MCP-1 and CCR2 genes with the risk of Parkinson’s disease

Studies investigating the impact of polymorphisms on monocyte chemotactic protein-1 (MCP-1) and CC chemokine receptor (CCR2) on the susceptibility of Parkinson's disease (PD) have reported inconsistent results. Owing to mixed and inconclusive results, we conducted a meta-analysis to systematically summarize and clarify the association between the two gene polymorphisms and PD risk. We performed a meta-analysis of five eligible studies to summarize the data describing the association between PD risk and polymorphisms in MCP-1 A2518G and CCR2 V64I. The association was evaluated by calculating the odds ratios (ORs) with the corresponding 95% confidence intervals (CIs). A significant increased risk of PD was observed in the MCP-1 A2518G polymorphism in allele model (G vs. A: OR 1.12, 95% CI 1.01-1.25, p = 0.03). The dominant model of MCP-1 A2518G genotype showed no significant association with PD risk, while the risk tendency was increased (AG + GG vs. AA: OR 1.20, 95% CI 1.00-1.42, p = 0.05). In addition, CCR2 V64I polymorphism showed no significant association with PD risk (I vs. V: OR 0.33, 95% CI 0.06-1.92, p = 0.22; VI + II vs. VV: OR 1.00, 95% CI 0.83-1.21, p = 0.99). In subgroup analysis by ethnicity, no significant difference was found in both Caucasians and Asians between CCR2 V64I polymorphism and PD risk, while a significant statistical association was identified in Asians between MCP-1 A2518G polymorphism and PD risk. When the data were stratified by study area, the increased risk of PD was observed only in studies conducted in China. In summary, the present meta-analysis suggests that genetic polymorphisms of MCP-1 A2518G may influence the susceptibility of PD in Asian countries, especially in China. However, CCR2 V64I polymorphism is not correlated with PD risk. The results should be interpreted with caution due to limited sample and heterogeneity. Large scale and well-designed studies are needed to validate our findings.

Novel association of five HLA alleles with HIV-1 progression in Spanish long-term non progressor patients.

Certain host genetic variants, especially in the human leucocyte antigen (HLA) region, are associated with different progression of HIV-1-induced diseases and AIDS. Long term non progressors (LTNP) represent only the 2% of infected patients but are especially relevant because of their efficient HIV control. In this work we present a global analysis of genetic data in the large national multicenter cohort of Spanish LTNP, which is compared with seronegative individuals and HIV-positive patients. We have analyzed whether several single-nucleotide polymorphisms (SNPs) including in key genes and certain HLA-A and B alleles could be associated with a specific HIV phenotype. A total of 846 individuals, 398 HIV-1-positive patients (213 typical progressors, 55 AIDS patients, and 130 LTNPs) and 448 HIV-negative controls, were genotyped for 15 polymorphisms and HLA-A and B alleles. Significant differences in the allele frequencies among the studied populations identified 16 LTNP-associated genetic factors, 5 of which were defined for the first time as related to LTNP phenotype: the protective effect of HLA-B39, and the detrimental impact of HLA-B18, -A24, -B08 and –A29. The remaining eleven polymorphisms confirmed previous publications, including the protective alleles HLA-B57, rs2395029 (HCP5), HLA bw4 homozygosity, HLA-B52, HLA-B27, CCR2 V64I, rs9264942 (HLA-C) and HLA-A03; and the risk allele HLA bw6 homozygosity. Notably, individual Spanish HIV-negative individuals had an average of 0.12 protective HLA alleles and SNPs, compared with an average of 1.43 protective alleles per LTNP patient, strongly suggesting positive selection of LTNP. Finally, stratification of LTNP according to viral load showed a proportional relationship between the frequency of protective alleles with control of viral load. Interestingly, no differences in the frequency of protection/risk polymorphisms were found between elite controllers and LTNPs maintaining viral loads <2.000 copies/mL throughout the follow-up.

Macrophage density in early surveillance biopsies predicts future renal transplant function

Inflammation impairs renal allograft survival but is difficult to quantify by eye at low densities. Here we measured leukocyte abundance in early surveillance biopsies by digital image analysis to test for a role of chemokine receptor genotypes and analyze the predictive value of leukocyte subsets to allograft function. In six-week surveillance biopsies, T-cell (CD3), B-cell (CD20), macrophage (CD68), and dendritic cell (CD209) densities were assessed in whole slide scans. Renal cortical CD3, CD20, and CD68 were significantly higher in histologic rejection. The CCR2 V64I genotype was associated with lower CD3 and CD209 densities. Above-median CD68 density was significantly associated with lower combined patient and graft survival with a hazard ratio of 3.5 (95% confidence interval 1.1-11.0). Both CD20 and CD68 densities inversely correlated with estimated glomerular filtration rate (eGFR) four years after transplantation. Additionally, CD68 correlated with eGFR loss. Among histological measurements including a complete Banff classification, only CD68 density was a significant predictor of an eGFR under 30ml/min after four years (odds ratio 7.4, 1.8-31.0) and part of the best eGFR prediction set in a multivariable linear regression analysis of multiple clinical and pathologic parameters. In a second independent cohort, the original CD68 median maintained its discriminative power for survival and eGFR. Thus, digital high-resolution assessment of CD68+ leukocyte infiltration significantly improves prognostic value of early renal transplant biopsies.

Chemokine and Chemokine Receptor Polymorphisms in Bipolar Disorder.

ObjectiveBipolar disorder (BD) is a debilitating psychiatric disease with unknown etiology. Recent studies have shown inflammation as a potential contributing factor of BD pathogenesis. However, potential associations between chemokine and chemokine receptor polymorphisms and BD have been fundamentally understudied. To identify participation of chemokines in BD pathogenesis, we examined genetic variants of several chemokine and chemokine receptor genes.MethodsThe study population comprised 200 patients with BD and 195 age- and sex-matched healthy controls. Genotyping of monocyte chemotactic protein 1 (MCP-1) A2518G, CCR2 V64I, CCR5 Δ32, CCR5 A55029G, stromal cell-derived factor 1 (SDF-1) 3'A, and CXCR4 C138T polymorphisms was performed using polymerase chain reaction and restriction enzyme digestion.ResultsWe found that CCR5-Δ32 II and CXCR4-C138T C+ genotype frequencies contributed to an increased risk for BD. However, no statistical significance could be obtained with these genotypes after Bonferroni correction. A significant asssociation was only found with MCP-1 GG and G+ genotypes, which were markedly more prevalent in patients with BD and these genotypes seemed to significantly increase the risk for BD even after Bonferroni correction.ConclusionOur findings indicate an association between genetic variants of certain chemokine and chemokine receptor (especially MCP-1) genes and BD. The exact mechanisms by which these variants contribute to BD pathogenesis and their clinical implications need to be further investigated.

Genetic variants of chemokine CCL2 and chemokine receptor CCR2 genes and risk of prostate cancer.

Chemokines and their receptors acts as mediators of migration of immune cells to the site of inflammation and deregulated inflammatory response is associated with increased risk of cancer. We performed a case-control study to analyze the frequencies of CCL2 (I/D, rs3917887), -2518 (A > G, rs1024611), and CCR2 (G > A, rs1799864) polymorphisms for prostate cancer (PCa) risk. In this hospital-based case-control study, histologically confirmed 195 PCa patients and 250 unrelated healthy controls of similar ethnicity were genotyped by PCR-RFLP. The result showed that heterozygous ID (odds ratio (OR) = 1.71; p = 0.010) carrier genotype of CCL2 gene were at increased risk for developing PCa. Variant allele D carriers (ID + DD) demonstrated a 1.67-fold increased risk (OR = 1.67; p = 0.010), suggesting a dominant effect model involved in PCa risk. Similarly, variant allele D of CCL2 gene also had a higher risk (OR = 1.53; p = 0.040) for developing PCa. High risk to PCa was also observed with respect to diplotypes, I-G (OR = 1.83; Bonferroni corrected p value (P c) = 0.004) and D-A (OR = 2.11; P c = 0.004) of CCL2 I/D and -2518 (A > G). In association of genotypes with clinic-pathological grade of tumor, homozygous DD (OR = 7.40; P c = 0.042) and variant allele carrier ID + DD (OR = 2.42; P c = 0.036) genotypes of CCL2 gene conferred risk in high Gleason grade tumor of PCa. We observed a significantly enhanced risk for PCa due to interaction between CCL2 I/D, -2518 (A > G), and CCR2 (G > A) genotypes. However, -2518 (A > G) and CCR2 V64I (G > A) gene polymorphisms were not significantly associated with PCa risk. Our results supported that CCL2 I/D gene variant contribute to the susceptibility and clinic-pathological characteristic of PCa and could be considered as an important risk factor for this malignancy in North Indian men.

Association of chemokine receptor gene variants with HIV-1 genotype predicted tropism.

As a switch from chemokine (C-C motif) receptor 5 [CCR5 (R5)] to chemokine (C-X-C motif) receptor 4 [CXCR4 (X4)] HIV-1 tropism is associated with symptomatic and AIDS stages of infection, while chemokine receptor gene variants modify the tempo of HIV disease progression, we aimed to analyse the association between pretreatment HIV-1 tropism and chemokine polymorphisms known to restrict disease progression. V3 genotype tropism prediction was performed in a group of 221 treatment-naïve patients, with subsequent CCR5 Δ32 (rs333), CCR2 V64I (rs1799864), CCR5 promoter (-627 C/T; rs1799988) and CX3CR1 V249I (rs3732378) genotyping performed in 206 patients. Alleles with a protective effect were assigned positive values while risk alleles were assigned negative values to calculate genetic scores. χ(2) tests, Mann-Whitney U-tests and logistic and linear regression models were used for statistical analyses. R5 tropism was found in 85.5% of patients (n = 189) using a false positive rate (FPR) of 5.75% and in 72.8% of patients (n = 161) using an FPR of 10%. A higher frequency of the 5.75% FPR predicted R5 tropism was associated with the CX3CR1 A allele (P = 0.027). Lower additive genetic scores were associated with an increased frequency of 5.75% FPR predicted R5 tropism (P = 0.0059), with the trend confirmed by logistic regression [odds ratio (OR) 0.5819; 95% confidence interval (CI) 0.3457-0.9795; P = 0.0416]. Viral load tended to increase with decreasing genetic score in the logistic regression analysis (slope = -0.127 ± 0.076; P = 0.095; r(2) = 0.161). The CX3CR1 A allele and lower genetic scores may restrict the switch of HIV-1 tropism from R5 to X4. This effect may be associated with the amount of co-receptor on the cell surface. Chemokine receptor gene polymorphisms influence both disease progression and tropism variability.

Impact of CCL2 and Its Receptor CCR2 Gene Polymorphism in North Indian Population: A Comparative Study in Different Ethnic Groups Worldwide

Chemokine are small, inducible pro-inflammatory cytokines involved in many biological processes, such as migration of leukocytes, atherosclerosis, angiogenesis, tumor growth, and metastasis. Chemokine are also known to influence tumor cell's activity. Specifically, tumor cells express chemokine receptors in a non random manner suggesting a role of chemokine in metastatic destination of tumor cells. The present study was conducted to determine distribution of (Chemokine receptor 2) CCR2 V64I, Chemokine ligand 2 CCL2 I/D, and CCL2 2518 A>G gene polymorphisms in North Indian population and compare with different populations globally. Polymerase chain reaction (PCR)-based analysis was conducted in 200 normal healthy individuals of similar ethnicity. Allelic frequencies in wild type (GG) of CCR2 V64I G>A were 63% G; CCL2 I/D 42% II; CCL2 2518 A>G 40.5% A. The minor variant allele frequency in our population was as follows: 19.5% for CCR2 V64I, 35.5% for CCL2 I/D, 35.3% for CCL2 2518 A>G. We further compared frequency distribution for these genes with various published studies in different ethnicity. Our results suggested that frequency in chemokine genes exhibit distinctive pattern in India that could be attributed to ethnicity variation. This could assist in high-risk screening of human exposed to environmental carcinogens and cancer predisposition in different ethnic groups. Thus, they signify an impact of ethnicity and provide a basis for future epidemiological and clinical studies.

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.

MCP‐1 and CCR2 gene variants in oral squamous cell carcinoma

We aimed to investigate a possible association of the MCP-1 and CCR2 polymorphisms with the risk of developing oral squamous cell carcinoma (OSCC). MCP-1 A2518G and CCR2 V64I gene polymorphisms were performed by polymerase chain reaction and restriction fragment length polymorphism, in 129 patients with OSCC and 140 healthy control subjects. Individuals who had G allele and GG genotype of MCP-1, and 64I allele and wt/64I genotype of CCR2 had increased risk for OSCC (P<0.05.) In contrast, individuals with CCR2 wt/wt genotype seem to be protected from OSCC (P < 0.01). Haplotype analysis revealed that MCP-1G: CCR2 64I haplotype frequencies were significantly higher in patients than those of controls (P = 0.001). We can suggest that the G allele of MCP-1 and 64I allele of CCR2 may be risk factors for OSCC.

The Role of the CCR2 Gene Polymorphism in Abdominal Aortic Aneurysms

Chronic inflammation play an important role on abdominal aortic aneurysms (AAA) formation. Chemokine receptor-2 (CCR2) is involved in regulation of the inflammatory response. However, relation between CCR2 polymorphism and AAA formation in human has not yet been investigated. In this study, we aimed to investigate the relationship between AAA and CCR2-V64I gene polymorphism. In this study, 100 consecutive patients with AAA and 138 individuals with normal aortic diameter were included. CCR2-V64I gene polymorphism were analyzed by PCR-RFLP technique. Genotype distribution and allele frequencies of CCR2-V64I gene polymorphism in patients with AAA and healthy subjects were compared. CCR2 heterozygote V64I polymorphism and allele frequency were more frequently observed in the AAA group (p = 0.01, p = 0.004). Significant relationship was observed between CCR2 V64I polymorphism (OR:2.31, 95% CI:1.19-4.46, p = 0.01) and presence of AAA in multivariate regression analysis. The present study, showed us a relationship between CCR2-V64I polymorphism and AAA.

Genetic polymorphism of CCR2‐64I increased the susceptibility of hepatocellular carcinoma

The purpose of this study was to investigate genetic impact of monocyte chemoattractant protein-1 (MCP-1) and its receptor chemokine receptor-2 (CCR2) gene polymorphisms on the susceptibility and clinicopathological characteristics of hepatocellular carcinoma (HCC). A total of 446 subjects, including 344 healthy controls and 102 patients with HCC, were recruited in this study and subjected to PCR-RFLP to estimate the impact of these two polymorphic variants on HCC. No relationship between MCP-1 -2518G/A gene polymorphism and HCC risk was found among our recruited HCC patients and healthy controls. However, there was a significantly increased risk (AOR = 1.91; 95% CI = 1.11-3.29) of having HCC among subjects with GA heterozygotes of CCR2 V64I after adjusting for other confoundings. There was no synergistic effect between gene polymorphism and environmental risk factors, including tobacco and alcohol consumptions, as well as clinicopathological parameters of HCC for MCP-1 -2518G/A and CCR2 V64I genes, respectively. CCR2-64I gene polymorphism is an important factor for the susceptibility of HCC but it might not influence the clinical pathological progression of HCC, and the contribution of CCR2-64I gene polymorphism on the susceptibility of HCC could be not through the affection of liver injury-related clinical pathological characteristics.

Genetic correlates of protection against HIV infection: the ally within

Repeated exposure to HIV does not necessarily result in infection and HIV infection does not inevitably lead to the development of the AIDS. Multiple immunological and genetic features can confer resistance to HIV acquisition and progression at different steps in viral infection; a full understanding of these mechanisms could result in the development of novel therapeutic and vaccine approaches for HIV infection. In this review, we focus on the genetic mechanisms associated with resistance to HIV infection and to the progression to AIDS.

Effects of CCR2 and CCR5 Polymorphisms on HIV-1 Infection in Thai Females

Polymorphisms in CCR2 and CCR5 genes reportedly affect HIV-1 transmission and disease progression in HIV-1-infected individuals. In the study presented here, we examined the effects of CCR2 and CCR5 polymorphisms on HIV-1 transmission in 74 Thai females who were exposed to HIV but seronegative (ESN) and in 347 HIV-seropositive females. We found that the combination of 2 non-synonymous substitutions, CCR2 V64I and CCR5 G316A, tended to occur more frequently in ESN females (2 of 74) than in HIV-1 infected females (1 of 347) (P = 0.08). This suggested that non-synonymous substitution in the CCR5 gene also affects HIV-1 transmission in an Asian population in which the CCR5-Delta32 is very rare.

Genetic control of chemokines in severe human internal carotid artery stenosis

Background and purpose: Atherosclerosis is an inflammatory disease. Chemokines and chemokine receptors are known to be involved in atherogenesis. Common single nucleotide polymorphisms (SNPs) affect transcription in response to inflammatory stimuli. The aim of this study was to evaluate the correlations between MCP-1, RANTES, SDF-1, CCR2, and CCR5 gene polymorphisms with increased risk of internal carotid artery (ICA) stenosis. Methods: Hundred and twelve patients, consecutively recruited for ICA occlusive disease, and 282 controls were genotyped for MCP-1-2518G, RANTES-403A, CCR5Δ32, CCR2 V64I, and SDF-1-801A polymorphisms. Results: The frequency of the SDF-1A allele was significantly different between cases and controls: 0.32 vs. 0.20, respectively (OR 1.81; 95% CI 1.25–2.60; p = 0.007). The frequency of the RANTES-403G allele was significantly higher in patients with stenosis >70% (OR, 2.45; 95% CI 1.12–5.71; p = 0.015). No significant differences were observed with the other polymorphisms. Conclusion: The reported results seem to correlate the polymorphisms of the genes encoding for SDF-1, RANTES with pathogenesis and progression of ICA occlusive disease. Although suggestive, these results need confirmation in prospective cross-sectional studies.

Chemokine Receptor Gene Polymorphisms and Severity of Acute Graft-Versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation from Sibling Donors.

Background: Single nucleotide polymorphisms (SNPs) and other genetic variations in various genes involved in the immune response have been variably associated with acute graft-versus-host-disease (GVHD). The interaction of chemokines with their receptors is crucial for organ-specific recruitment of immune cells. Trafficking of recipient antigen presenting cells as well as donor lymphocytes between lymph nodes and target tissues are especially important events in acute GVHD pathogenesis. In this pilot, retrospective study, we sought to examine the role of recipient and donor chemokine receptor gene polymorphisms in determining the incidence of severe acute GVHD in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) from matched sibling donors.Methods: Patient and donor samples were genotyped for the following chemokine receptor polymorphisms: CCR5 -59029 A/G, CCR2 190 A/G (V64I), CX3CR1 745 A/G (V249I) and CX3CR1 839 C/T (T280M) and CCR5Δ32. Due to the extreme rarity of homozygosity for the Δ32 deletion in CCR5, the CCR5Δ32 homozygotes and heterozygotes were grouped together for analysis. The relationship between polymorphism genotypes and acute GVHD outcomes (Grade 0 vs Grades III/IV) were evaluated.Results: A total of 103 donor-recipient pairs were analyzed which included 58 recipients who experienced severe acute GVHD (Grades III/IV) and 45 recipients who did not develop acute GVHD (Grade 0). Compared to the wild type CCR5 allele, the presence of the CCR5Δ32 allele in the donor conferred an increased risk for severe acute GVHD (P=0.04). The odds ratio is estimated to be 6.16 (95% CI [0.73, 52.05]). Presence of CCR5Δ32 in the recipient was not associated with increased acute GVHD risk (P=0.14). For the CCR5 -59029 A/G polymorphism, there was the suggestion of a decreased trend for developing severe acute GVHD if the donor had the A/A genotype (P=0.09). A trend for an association with the incidence of severe acute GVHD was observed for the CCR2 V64I polymorphism in the recipient. (P= 0.08). Donor genotype for this polymorphism was not associated with severe GVHD (P=0.17). A trend towards increased incidence of severe GVHD was observed for the 745 A/G (V249I) polymorphism (P=0.1). No significant effect was observed for the CX3CR1 839 C/T (T280M) polymorphism in this study.Conclusions: CCR5Δ32 polymorphism in the donor was associated with severe acute GVHD in this study. This and other functional chemokine receptor polymorphisms are potential candidates for evaluation in large prospective studies in future to precisely determine their association with acute GVHD.

Distribution of CCR2 polymorphism in HIV‐1‐infected and healthy subjects in North India

Substitution of V64I in CCR2 relates to delayed progression to AIDS and protects against HIV-1 infection. We examined the distribution of V64I in HIV-infected and healthy North Indian subjects. No significant difference in the allele or genotype distribution of CCR2 V64I polymorphism was observed, indicating that there is no association between CCR2 V64I polymorphism and susceptibility to HIV infection in North Indian population.

RANTES, MCP-1, CCR2, CCR5, CXCR1 and CXCR4 Gene Polymorphisms are not Associated with the Outcome of Hepatitis B Virus Infection: Results from a Large Scale Single Ethnic Population

Recovery from hepatitis B virus (HBV) infection depends on the cellular immune responses. Chemokines and their receptors play significant roles in immune defense. This study was undertaken to investigate the association between HBV infection and single nucleotide polymorphisms (SNPs) of genes for the chemokines and their receptors. Between March 2002 and February 2004, a total of 957 single ethnic Korean patients were enrolled into two different groups; "HBV clearance group" (n=350), who have recovered from HBV infection, and "HBV persistence group" (n=607), who were repeatedly HBsAg-positive. The HBV persistence group was subdivided into "inactive carrier" and "HBV progression group (chronic hepatitis and cirrhosis)". We assessed polymorphisms in regulated and normal T-cell expressed and secreted (RANTES) at position -403, monocyte chemoattractant protein-1 (MCP-1) at position -2518, CCR2 V64I, CCR5 -2459, CXCR1 S276T and CXCR4 I138I using single primer extension assay. Genotype distributions of the "HBV clearance versus persistence group" and "inactive carrier versus HBV progression group" were compared. On the basis of unconditional logistic regression analysis with adjustment for age and sex, no statistically significant association with susceptibility to persistent HBV infection was observed with RANTES -403, MCP-1 -2518, CCR2 V64I, CCR5 -2459, CXCR1 S276T, and CXCR4 I138I polymorphisms. In addition, no association of analyzed SNPs with HBV disease progression was found.

Genetic Polymorphism of the Chemokine Co-Receptors CCR5, CXCR4 and CCR2 in Bulgarians Living with HIV

ABSTRACTThe aim of this study was to investigate the most spread genetic polymorphisms of the chemokine co-receptors CCR5, CXCR4 and CCR2—namely the allele frequency of CCR5del32, SDF-1 3'A and CCR2 V64I in 177 Bulgarians living with HIV, as well as to correlate the results to the clinical course of HIV-infection and the same allele frequency for general population. The persons studied were of different duration of HIV-infection—registered during the period 1987–2004. Fourteen persons (7.9%) showed slow progression to AIDS, received therapy after no treatment for 7–10 years and were considered Long Term Survivors (LTSs). All HIV(+)s have been screened for CCR5 (CCR5del32) and 48 - for CXCR4 (SDF-1) (SDF-1 3'A) and CCR2 (CCR2 V64I) polymorphisms. No one from HIV positives has been found with a homozygous—CCR5del32/CCR5del32 - status, 6 out of all studied (3.2%) had heterozygous (CCR5/CCR5del32) genotype (only two LTSs). Seven out of 48 persons studied (14.6 %) had homozygous (SDF-1 3'A/SDF- 1 3'A) genotype, (3 - LTSs), another 12 (25%) showed heterozygocity for CCR2 (CCR2/CCR2V64I - 2 - LTSs). The LTSs heterozygous by CCR5 (CCR5/CCR5del32), those displaying (SDF-1 3'A/SDF-1 3'A) homozygocity and both (13.33%) demonstrating (CCR2/CCR2V64I) heterozygous genotype were different persons. Although low numbers of persons studied, the results obtained coincide well to the literature ones. The genetic studies will be used to predict the results of HAART treatment as well as the onset to AIDS.

Late survival after heart transplantation: are we getting better at long-term management?

migration of these cells to the site of inflammation. Recently single nucleotide polymorphisms (SNPs) in some chemokine receptors have been shown to alter leukocyte recruitment and have been linked to atherosclerosis. We therefore analyzed their importance in a cardiac transplant recipient (CTR) cohort and their association with transplant vasculopathy (TV). Methods: 84 patients were enrolled from our heart transplant clinic. The following SNPs were genotyped: CX3CR1 V249I and T280M, CCR2 V64I and CCR5 A59029G. In 48 CTR two or more angiograms were available to compare transplant vasculopathy (TV) development: 25 subjects were judged to have TV. Mean time from transplant was 7.3 2.8 years. Results: The frequencies of the SNP alleles were in accordance with published data. Demographic data and pretransplant diagnosis were not significantly different among the SNP genotypes. The table shows significant associations with TV for the variant alleles CX3CR1 I249, CX3CR1 M280 and CCR2 I64. In conclusion, common SNPs of the genes encoding the receptors of fractalkine and MCP-1 may have a pathogenic role in the development of TV. The likely mechanism underlying these associations is a modified leukocyte-graft interaction in the vessel wall. Further research is needed to replicate the associations and to establish these mechanisms.

CCR5 Promoter Polymorphism Influences the Interferon Response of Patients with Chronic Hepatitis C in Japan

Objective: Chemokines and chemokine receptors play important roles in the pathogenesis of chronic hepatitis C. Here, we explore the influence of genetic polymorphisms of chemokine and chemokine receptors such as regulated upon activation and T cell secreted (RANTES), CC chemokine receptor 5 (CCR5) and CCR2 on the outcome of interferon (IFN) monotherapy. Methods: In a cohort of 105 patients with chronic hepatitis C as well as in 50 sustained responders and 55 nonresponders the presence of polymorphisms such as CCR5-Δ32, CCR5 59029G/A, CCR2 V64I and RANTES –403G/C was determined. Results: Gender, age, liver histological staging, pretreatment ALT levels, total dose of IFN and frequencies of polymorphisms (CCR2 V64I and RANTES –403G/C) did not significantly differ between the two groups. A low viral load, hepatitis C virus (HCV) serotype 2 and CCR5 59029G/G were significantly associated with a higher probability of a sustained response (p < 0.01, p < 0.05, p < 0.05, respectively). Multiple logistic regression analysis showed that a low viral load, HCV serotype 2 and CCR5 59029G/G were independently associated with a sustained response [odds ratio 3.980 (1.647–9.621), p = 0.002; 3.584 (1.439–8.924), p = 0.006; 3.638 (1.163–11.379), p = 0.026, respectively]. Conclusion: These findings indicate that CCR5 59029 is a host genetic factor that is associated with responses to IFN therapy among Japanese patients with chronic hepatitis C.