Abstract
Chemokines and chemokine receptors are major mediators of leukocyte trafficking into the sites of the immune response. They participate in defence against microbial infection, in Th1/Th2 polarization of the immune response, allograft rejection and angiogenesis/angiostasis as well as in tumorigenesis and metastasis. To date, several functional polymorphisms of chemokine and chemokine receptor genes have been discovered that are able to deregulate chemokine system and, therefore, they may interfere with the pathogenesis of a large number of inflammatory and other diseases. In this review we focus on the known polymorphisms of two chemokines: CCL2, CCL5 and their corresponding receptors (CCR2, CCR5) and we also discuss their associations with susceptibility and progression to selected immune-mediated diseases. Based on relevant literature this article gives a short overview of case-control and family studies regarding effect of the genetic factors on diseases such as coronary artery disease, systemic lupus erythematosus, diabetes mellitus, lung diseases and others. Recent advance in the identification of chemokine genetic background of the diseases could provide opportunity for pharmacological treatment. However, we need more information about posttranscriptional events to understand functional relevance of polymorphisms and to discovery new avenues to blocking disease development.
Highlights
Chemokines are low-molecular-weight molecules characterized by the presence, as a common structural pattern, of four cysteine residues and are divided into four main families (CXC, CC, C and CX3C) according to the number of amino acids between the residues of the two most amino-proximal cysteines[1, 2].Chemokines are trophic molecules; that is, they signal leukocytes to move in a specific direction, along gradient of chemokine concentration
3.3.1 Atherosclerosis When Simeoni et al explored distribution of RANTES-403 G/A in coronary artery disease (CAD), -403*A variant was associated with increased risk of CAD and it remained significant after multivariate adjustment[16]
By contrast to the Multicenter acquired immunodeficiency syndrome (AIDS) Cohort Study (MACS) study Zhao et al observed that the haplotype 1 (-403G, -28C) and -403*G allele are over-represented in Chinese HIV positive patients, whereas -403 A/A genotype was associated with lower susceptibility to HIV infection[88]
Summary
Chemokines and chemokine receptors are major mediators of leukocyte trafficking into the sites of the immune response. They participate in defence against microbial infection, in Th1/Th2 polarization of the immune response, allograft rejection and angiogenesis/angiostasis as well as in tumorigenesis and metastasis. Several functional polymorphisms of chemokine and chemokine receptor genes have been discovered that are able to deregulate chemokine system and, they may interfere with the pathogenesis of a large number of inflammatory and other diseases. In this review we focus on the known polymorphisms of two chemokines: CCL2, CCL5 and their corresponding receptors (CCR2, CCR5) and we discuss their associations with susceptibility and progression to selected immune-mediated diseases
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