Elsevier

Human Immunology

Volume 68, Issue 12, December 2007, Pages 980-985
Human Immunology

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

https://doi.org/10.1016/j.humimm.2007.10.007Get rights and content

Summary

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 χ2, 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.

Introduction

Systemic lupus erythematosus (SLE) is a chronic and systemic autoimmune disease that is characterized by autoantibody production, abnormalities of immune–inflammatory system function, and inflammatory manifestation in several organs [1]. Genetic factors play an important role in the susceptibility to its development. Particular attention has been focused on the association of disease with genetic markers located within the major histocompatibility complex region on the short arm of chromosome 6. The mechanism by which these genes determine susceptibility is not completely understood and the participation of non-HLA genes has been suggested [2], [3], [4]. In this respect, there are several lines of evidence that chemokines and cytokines play an important role in the inflammatory development and progression of autoimmune diseases such as SLE [5], [6], [7], [8]. According to previous reports, monocyte chemoattractant protein 1 (MCP-1), stromal cell-derived factor-1 (SDF-1), and regulated on activation normal T cell expressed and secreted (RANTES) are candidate chemokines for study in SLE. MCP-1 and RANTES are involved in the physiology and pathophysiology of acute and chronic inflammatory processes by recruitment of monocytes, T lymphocytes, and eosinophils to sites of inflammation [9], [10]. High serum levels of these chemokines have been reported in SLE patients [11]. SDF-1 (CXCL12) is a chemokine that plays an important role in the regulation of migration, proliferation, and differentiation of hematopoietic cells [12], [13]. In the mouse model NZB/W, SDF-1 participates in the chemotaxis, proliferation, and survival of B1a cells, which produce pathogenic autoantibodies directed against nuclear cells, including anti-dsDNA, which carry a lethal nephritis [14]. Several reports suggest that some genetic variants of the genes that code these chemokines can affect the transcriptional activity and subsequent protein expression in humans [15], [16], [17]. In the distal region of the MCP-1 gene, a guanine (G) to adenine (A) transition was identified at position -2518 upstream from the major transcription site (MCP-1-2518), and this polymorphism has been associated with circulating MCP-1 levels. When stimulated by IL-1 β, monocytes/macrophages from homozygous G/G individuals produce up to 1.7 times more MCP-1 than those homozygous for A/A [15]. A genetic polymorphism exists in the nontranslated 3′ region (3′UTR) of gene SDF-1 in position 801, which seems to increase the amount of SDF-1 messenger RNA, with an apparently protective effect against rapid progression toward AIDS [18]. The RANTES-28 polymorphism has a modest effect on the increase of the transcription of the gene [19] and has been associated with high initial levels of antinuclear antibodies (ANAs), low levels of C3, and a high incidence of neuropsychiatric lupus in Chinese children with SLE [20]. Also, some of these polymorphisms have been analyzed in case–control studies in SLE patients with heterogeneous results in different populations [5], [6], [21], [22], [23]. Thus, the aim of the present study was to investigate the role of MCP-1, SDF-1, and RANTES polymorphisms as contributors to genetic susceptibility and clinical manifestation of the SLE in Mexican Mestizo patients.

Section snippets

Studied population

The study included 242 unrelated SLE Mexican patients, 220 women and 22 men. All patients fulfilled at least four of the American College of Rheumatology criteria for SLE [24]. One hundred twenty-one of the patients showed lupus nephritis, 73 (60.3%) of which were confirmed with biopsy. The no-biopsy group satisfied at least four of the following criteria: (i) creatinine clearance < 70 mL/minute, (ii) proteinuria greater than 1 g/24 hours, (iii) granular and erythrocytic casts in urine, (iv)

Results

A total of 242 patients with SLE diagnosis were included in the study (220 women and 22 men). Demographical and clinical characteristics of the studied patients are shown in Table 1. Clinical manifestations were presented at least once during the evolution period of the disease, measured from the time of diagnosis to the moment when a blood sample was drawn.

Allele and genotype frequencies of MCP-1-2518, SDF-1 G801A, and RANTES-28 polymorphisms in SLE patients and healthy controls are shown in

Discussion

Several lines of evidence suggest that chemokines and cytokines play an important role in the inflammatory process and progression of SLE [6], [7], [8]. Chemokines such as MCP-1, SDF-1, and RANTES have been involved in inflammatory pathologies. In the present study, we assessed the association between MCP-1-2518, SDF-1 G801A, and RANTES-28 polymorphisms and the genetic susceptibility to developing SLE in a group of Mexican patients. The relationship between these polymorphisms and

Acknowledgments

The authors are grateful to the study participants. Institutional review board approval was obtained for all sample collections.

References (34)

  • R. Mehrian et al.

    Synergistic effect between IL-10 and bcl-2 genotypes in determining susceptibility to systemic lupus erythematosus

    Arthritis Rheum

    (1998)
  • M. Aoki et al.

    Mast cells in basal cell carcinoma express VEGF, IL-8 and RANTES

    Int Arch Allergy Immunol

    (2003)
  • G.H. Tesch et al.

    Monocyte chemoattractant protein 1-dependent leukocytic infiltrates are responsible for autoimmune disease in MRL-Fas(lpr) mice

    J Exp Med

    (1999)
  • L.C. Lit et al.

    Raised plasma concentration and ex vivo production of inflammatory chemokines in patients with systemic lupus erythematosus

    Ann Rheum Dis

    (2006)
  • H.E. Broxmeyer et al.

    Effects of CC, CXC, C, and CX3C chemokines on proliferation of myeloid progenitor cells, and insights into SDF-1-induced chemotaxis of progenitors

    Ann NY Acad Sci

    (1999)
  • C.C. Bleul et al.

    A highly efficacious lymphocyte chemoattractant, stromal cell-derived factor 1 (SDF-1)

    J Exp Med

    (1999)
  • K. Balabanian et al.

    Role of the chemokine stromal cell-derived factor 1 in autoantibody production and nephritis in murine lupus

    J Immunol

    (2003)
  • Cited by (45)

    • MCP-1: Function, regulation, and involvement in disease

      2021, International Immunopharmacology
      Citation Excerpt :

      The MCP-1 A-2518G polymorphism is not involved in the development of Alzheimer’s disease [29]. MCP-1 polymorphism is also associated with systemic lupus erythematosus (SLE), in Mexican population there is a moderate association of MCP-1-2518 with the genetic susceptibility to SLE while in Indian SLE patients it has been correlated with renal disorders [30,31]. In early phase of inflammation in gastric ulceration, the expression of MCP-1 is induced by tumor necrosis factor-α (TNF-α) which further regulates the leukocyte recruitment, thus playing key role in the ulceration [32].

    • A functional SNP MCP-1 (−2518A/G) predispose to renal disorder in Indian Systemic Lupus Erythematosus patients

      2017, Cytokine
      Citation Excerpt :

      Various studies on genetic polymorphisms in regulatory region of the MCP-1 gene have been proposed to be associated with clinical manifestations in SLE patients. A biallelic A/G polymorphism at −2518 of the MCP-1 gene has been described to be associated with lupus nephritis [11]. This nucleotide base transition influences overall transcriptional activity and produces more MCP-1 transcripts and protein in SLE patients homozygous for a variant allele G among SLE patients.

    • CCR5 promoter region polymorphisms in systemic lupus erythematosus

      2024, International Journal of Immunogenetics
    View all citing articles on Scopus
    View full text