The CCR5Δ32 polymorphism as a pre-eclampsia susceptibility marker: an evaluation in Brazilian women

Abstract

a cluster with other chemokine receptor genes [5]. the CCr5Δ32 (rs333) is an allelic variant of which 32 bp were deleted in the coding region resulting in a nonfunctional receptor. First described as a co-receptor for hIV-1 virus infection, this variant was also associated to several inflam-matory conditions (see Vargas et al. for a review). homozy-gous individuals for CCr5Δ32 do not express a functional protein, while heterozygous may express low amounts of the functional receptor when compared to the wild-type homozygous individuals.Pre-eclampsia, for instance, is one of the most common pregnancy complications and along with other hyperten-sive disorders, is a major contributor to maternal mortal-ity worldwide [6]. Despite its severity, the etiology of Pe is not fully elucidated, affecting 5–10% of all pregnan -cies globally. In Brazil, this disease accounts for more than 7 % of maternal–fetal mortality. thus, the understanding of such phenomenon is of great importance to elucidate the immunological mechanisms involved during the gesta-tional period. Pe is characterized, among others symptoms, by the occurrence of hypertension (diastolic blood pres-sure of ≥90 mm hg), edema and substantial proteinuria (≥300 mg in 24 h) at or after 20 weeks of gestation [7]. 6, Furthermore, Pe is characterized by events of endothelial dysfunction and excessive inflammation, mainly in the first trimester of pregnancy [6]. One of the pathophysiologi-cal mechanisms of Pe is a failure to develop an adequate blood supply to the placenta, leading to placental oxidative stress and excessive release of placental factors in mater-nal circulation. In addition, an inadequate trophoblast inva-sion results in an incomplete remodeling of uterine spiral arteries, being the main cause of placental ischemia in PeImmunogenetics laboratory, Department of[8, 9]. It is known that genetic factors play a role in pre-eclampsia. Also, an immune unbalance in pre-eclampsia has been reported. Altered cytokine production and marked Dear Sir,We read with interest the manuscript by Gurdol et al. [1] that suggested a protective effect of the CCr5Δ32 poly-morphic variant of the CCr5 gene in inflammation asso-ciated to pre-eclampsia (Pturkish women. e) in the CCr5Δ32 allelic variant was observed in a lower fre-quency among pre-eclamptic women as compared to con-trols, and therefore the authors suggested that its presence conferred protection against this disease. As it is well-estab-lished, chemokines are chemotactic cytokines involved in several cellular processes including innate immunity, cellu-lar recruitment, cell activation, induction of adhesion mol-ecules expression and inflammation [2]. Chemokine recep-tors (CCr) are members of the G protein-coupled receptors and present seven transmembrane domains, being con-sidered as important determinants of early inflammatory responses [2]. Different works already evaluated the asso-ciation of CCr genes polymorphisms as well as cytokine levels and the inflammatory state and pathogenesis of pre-eclampsia [3, 4]. CCr5 is a member of the CC chemokine receptors mainly expressed in immune system cells, such as macrophages and t lymphocytes. CCr5 plays an impor-tant role in migration of immune cells to inflammatory sites. It has been shown that chemokines are essential for the regulation of immune responses, being crucial in patho-genesis of both autoimmune and hypersensitivity-based diseases [2t]. he gene encoding CCr5 (