RANTES Polymorphisms Research Articles

The -2518 A/G MCP-1 and -403 G/A RANTES promoter gene polymorphisms are associated with psoriasis vulgaris.

Polymorphic variants of the genes encoding monocyte chemoattractant protein-1 (MCP-1/CCL2) and regulated upon activation normal T-cell expressed and secreted (RANTES/CCL5) and their protein serum levels have not been widely explored in psoriasis. To clarify the effect of the MCP-1 (-2518 A/G) and RANTES (-403 G/A) promoter gene polymorphisms on the risk and clinical manifestation of psoriasis. We enrolled 160 unrelated patients with psoriasis vulgaris and 160 healthy, unrelated, age- and sex-matched volunteers. The promoter gene polymorphisms were analysed using amplification refractory mutation system (ARMS)-PCR and single specific primer (SSP)-PCR. Serum levels of cytokines were measured using ELISA. The presence of the MCP-1-2518 GG genotype was statistically more frequent in patients and it was associated with an increased risk of psoriasis (OR = 1.94; P = 0.04). In patients with late-onset (≥ 40 years) psoriasis, the presence of the RANTES -403 AA genotype was statistically more frequent (OR = 3.65; P < 0.01) while -403 GG was less frequent (OR = 0.44; P < 0.01). Moreover, the A allele (AA or AG) in the -403 RANTES polymorphism was associated with an increased risk of developing severe psoriasis (OR = 2.02; P = 0.03). Serum levels of both chemokines were elevated. RANTES serum concentration was significantly higher in patients with Psoriasis Area and Severity Index > 15. The results of our analysis suggest that the -2518 A/G MCP-1 and -403 G/A RANTES promoter gene polymorphisms may be risk factors for psoriasis and may influence its clinical presentation.

A study on the association of autoantibodies, chemokine, and its receptor with disease activity in systemic lupus erythematosus in North Indian population

Systemic lupus erythematosus (SLE) is a chronic and complex autoimmune disease characterized by the production of autoantibodies against a spectrum of nuclear antigens. RANTES and its receptor CCR5 have been associated with the pathogenesis of SLE. The objective of this study is to analyze autoantibodies (DNA/RNA), allelic distribution of RANTES and the association of levels of RANTES and its receptor CCR5 in SLE patients in North Indian region. The RANTES-403 and RANTES-28 polymorphism in the promoter region of RANTES gene was studied in 80 patients and 80 healthy controls. The levels of chemokine RANTES, its receptor CCR5, anti-dsDNA, and anti-SSA antibodies levels were determined. Disease activity was assessed with the systemic lupus erythematosus disease activity index (SLEDAI) score. All the parameters were studied for statistical analysis by using t test (graph pad prism) and correlation by SPSS data. PCR-RFLP performed showed 28C/C and the 403G/G genotypes in both patients and controls, but no other genotypes such as 28C/G, 28G/G and 403A/G, 403A/A were found. Patients had higher levels of RANTES (1840.48 ± 739.42 vs. 835.44 ± 70.48 pg/ml; P < 0.0001) and its receptor CCR5 expression (26.49 ± 0.16 vs. 24.72 ± 3.02 %; P < 0.05) compared to controls. The levels of autoantibodies anti-dsDNA and anti-SSA were also higher in patients than controls. The patients showing elevated anti-dsDNA had negative correlation with SLEDAI score (P < 0.05) while borderline patients were not found to be correlated. In case of anti-Ro/anti-SSA antibody levels, the borderline patients showed a moderately significant negative correlation as compared to controls than patients with elevated autoantibody (P < 0.01). The levels of RANTES and CCR5 were also higher in case of patients than controls. But there was no significant correlation of RANTES and CCR5 with disease activity. We were unable to find an association of RANTES polymorphism with SLE in North Indian population in our sample. No significant difference in allele distribution of RANTES-28 and RANTES-403 in the sample of 160 individuals was detected. Of the two autoantibodies studied, anti-Ro/anti-SSA levels in borderline lupus patients appeared as an important parameter for monitoring/diagnosis of lupus patients.

Respiratory syncytial virus infection and chronic respiratory morbidity – is there a functional or genetic predisposition?

A systematic literature review has been undertaken. Respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) in infancy is associated with chronic respiratory morbidity. Premorbid abnormal lung function may predispose to RVS LRTI in prematurely born infants. Single-nucleotide polymorphisms in genes coding for IL-8, IL-19, IL-20, IL-13 mannose-binding lectin, IFNG and a RANTES polymorphism have been associated with subsequent wheeze following RSV LRTI in term-born infants.

RANTES, MCP-1 chemokines and factors describing rheumatoid arthritis

The MCP-1/CCL2 as well as RANTES/CCL5 chemokines are potent chemoattractants involved in immunoregulatory and inflammatory processes of rheumatoid arthritis. Recent studies demonstrated elevated levels of MCP-1 and RANTES in plasma, synovial fluid, and the synovial tissue of patients with RA. To examine the relationship among MCP-1 and RANTES single nucleotide polymorphisms and circulating levels and rheumatoid arthritis (RA), a total of 156 RA patients and 125 controls were recruited into the study. An association of −855 C/G MCP-1 polymorphism to IgM RF within the RA patients was observed. The lowest circulating levels of RANTES were observed in the AA variant of RANTES −403 G/A polymorphism. Furthermore, an association of −403 AA variant to circulating levels of IL-15 and IL-10 was found. No associations of factors describing rheumatoid arthritis (RFs, ANA, anti-CCP-positive/negative, DAS 28 score and number of swollen joints) with MCP-1 levels, genotype distribution, allelic frequencies and/or frequencies of haplotypes composed of all three studied polymorphisms in promoter region of MCP-1, and RANTES polymorphism were observed. We conclude that the RANTES promoter polymorphism is associated to circulating levels of RANTES, IL15 and IL10. However, our findings suggest that polymorphisms in the MCP-1 and RANTES gene promoters do not contribute significantly to the interindividual RA susceptibility and/or severity in Caucasians.

Relationship between &lt;i&gt;RANTES&lt;/i&gt; Polymorphisms and Respiratory Syncytial Virus Bronchiolitis in a Japanese Infant Population

Respiratory syncytial virus (RSV) is the most important virus associated with bronchiolitis in infants and young children. The regulated upon activation, normal T-cell expressed and secreted protein (RANTES, also known as CCL5) appears to be a key player in the etiology of RSV-infected airway inflammation. In this study, we genotyped three single-nucleotide polymorphisms in the RANTES gene: –403G/A, –28C/G, and In1.1T/C in 59 infants with severe RSV bronchiolitis and 201 control subjects. The frequencies of the –403G/A+A/A, –28C/G+G/G, and In1.1T/C+C/C genotypes were significantly lower in patients with severe RSV bronchiolitis than in control subjects, and the frequencies of the –403A, –28G, and In1.1C alleles were significantly lower in RSV patients than in control subjects. The present results suggest that RANTES polymorphisms may confer risk for severe RSV bronchiolitis.

Polymorphisms in theRANTESGene Increase Susceptibility to Active Tuberculosis in Tunisia

RANTES plays a pivotal role in attracting and activating various leukocyte populations that control Mycobacterium tuberculosis infection. The present study investigated the relationship between the RANTES polymorphisms (-28C/G; rs2280788, and -403G/A; rs2107538) and susceptibility to active tuberculosis (TB) in Tunisian populations. A total of 168 patients with pulmonary TB (pTB), 55 with extrapulmonary TB (epTB), and 150 control subjects were studied. Genotype analyses were carried out using polymerase chain reaction-restriction fragment length polymorphism method. We found that the -28 GG genotype was significantly associated with susceptibility to pTB (odds ratio [OR]=11.19; 95% confidence intervals [CI], 5.14-25; P corrected for the number of genotypes [Pc]=10(-8)) and epTB (OR=11.67; 95% CI, 4.74-29.33; Pc=10(-8)). However, the -28 CC genotype was found to be significantly associated with resistance to pTB (OR=0.08; 95% CI, 0.04-0.16; Pc=10(-8)) and epTB development (OR=0.11; 95% CI, 0.05-0.27; Pc=10(-8)). -403A allele was associated with increased risk development of epTB (OR=2.21; 95% CI, 1.18-4.14; p=0.007). G-G and A-C haplotypes and the AG/GC diplotype were associated with increase susceptibility to pTB (OR=7.88, 95% CI, 5.38-11.55; Pc=3.10(-8); OR=2.32, 95% CI, 1.32-4.11; Pc=3.10(-3); OR=13.26, 95% CI, 6.06-29.89; Pc=3.10(-8); respectively) and epTB (OR=6.64, 95% CI, 4-11.05; Pc=3.10(-8); OR=2.6, 95% CI, 1.26-5.35; Pc=12.10(-3); OR=11.26, 95% CI, 4.44-29.28; Pc=3.10(-8); respectively). Collectively, our findings suggested an association of the RANTES -28C/G and -403G/A functional polymorphisms with susceptibility to Mycobacterium tuberculosis infection in Tunisian populations.

RANTES Gene Polymorphisms and Asthma Risk: A Meta-Analysis

RANTES is a chemokine that assists the recruitment of inflammatory cells including eosinophils. Previous studies revealed that polymorphisms of RANTES were implicated in susceptibility to asthma, but a large number of studies reported apparently conflicting results. We performed a meta-analysis to investigate the association of these polymorphisms and asthma risk. Literature-based meta-analysis was supplemented by tabular data from investigation of all relevant studies regarding all polymorphisms of RANTES available before November 30, 2009, with investigation on potential sources of heterogeneity. Ten case/control studies were included in the meta-analysis, involving a total of 1706 cases and 1685 controls. In a combined analysis, no significant associations with asthma risk were found on these two polymorphisms (-403G/A and -28C/G) without any publication bias. For the -403G/A polymorphism, in subgroup analysis by ethnicity, no significant associations were found in Asians, Europeans or African-Americans; in subgroup analysis by age, no significant associations were found in adults or children. In subgroup analysis by atopic status, the -403G/A polymorphism was significantly associated with asthma risk in atopic asthma (dominant model [OR = 1.38, 95% CI = 1.09-1.76, p = 0.009; P(het) = 0.10]; A vs. G model [OR = 1.25, 95% CI = 1.04-1.51, p = 0.02; P(het) = 0.11] and AG vs. GG model [OR = 1.37, 95% CI = 1.06-1.77, p = 0.02; P(het) = 0.14]). This meta-analysis suggested that RANTES gene -403G/A polymorphism would be a risk factor among atopic asthma patients. To further evaluate gene-to-gene and gene-to-environment interactions on RANTES polymorphisms and asthma risk, more studies with thousands of patients are required.

MCP-1, RANTES, and SDF-1 polymorphisms in Mexican patients with systemic lupus erythematosus

Chemokines and cytokines play an important role in the inflammatory development and progression of autoimmune diseases. The aim of the present study was to evaluate the role of MCP-1, SDF-1, and RANTES polymorphisms as susceptibility markers for systemic lupus erythematosus (SLE) in a group of Mexican patients. MCP-1-2518, SDF-1 G801A, and RANTES-28 polymorphisms were determined in 242 patients with SLE and 220 ethnically matched healthy controls by the polymerase chain reaction-restriction fragment length polymorphism technique. The differences between patients and healthy controls were evaluated by chi(2), Fisher's exact test, and Woolf method for odds ratio. A moderately increased frequency of MCP-1-2518 A allele (p = 0.033, pC = NS) and AA genotype (p = 0.017, pC = NS) existed in SLE patients compared with healthy controls. There was a relationship between polymorphisms and some clinical and laboratory characteristics. SLE patients with and without antiphospholipid syndrome demonstrated different distribution of SDF-1 G801A genotype frequencies. On the other hand, patients with leukopenia, anti-dsDNA, and antiphospholipid autoantibodies demonstrated different MCP-1-2518 genotype distribution compared with patients without these features. Our results suggest that MCP-1 polymorphism is moderately associated with the genetic susceptibility to SLE in Mexican individuals. The polymorphisms could be related to specific clinical and laboratory characteristics in these patients.

A Polymorphism That Reduces RANTES Expression Is Associated with Protection from Death in HIV‐Seropositive Ugandans with Advanced Disease

We investigated the effect of RANTES polymorphisms on human immunodeficiency virus type 1 (HIV-1) disease progression in an urban population of Uganda. HIV-positive individuals homozygous for the INT1.1C polymorphism, which had been associated previously with low RANTES expression, were less likely to die than were those with other genotypes (hazard ratio, 0.53 [95% confidence interval, 0.33-0.83]; P=.007). This report of a non-human leukocyte antigen genetic association with HIV-1 and/or acquired immunodeficiency syndrome disease progression in an African population reveals a genetic effect different from that reported elsewhere for African Americans and may impact therapeutic strategies targeting the RANTES pathway in HIV infection.