<i>CCR5Δ32</i>and the genetic susceptibility to rheumatoid arthritis in admixed populations: a multicentre study

Toson, Bruno; Santos, Eduardo José dos; Adelino, José Eduardo; Sandrin-Garcia, Paula; Crovella, Sérgio; Louzada‐Júnior, Paulo; Oliveira, Rejane Barbosa de; Pedroza, Larysse Santa Rosa Aquino; Sauma, Maria de Fátima Lobato da Cunha; Lima, Clayton Pereira Silva de; Barbosa, Fabíola Brasil; Brenol, Claiton Viegas; Xavier, Ricardo Machado; Veit, Tiago Degani

doi:10.1093/rheumatology/kew398

Cited by 9 publications

(15 citation statements)

References 8 publications

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“…According to a meta-analysis, rs3093024 and several other SNPs (single nucleotide polymorphism) in CCR6 are associated with RA in European and Asian populations [ 6 , 24 ]. At the same time, a 32-bp deletion in another chemokine receptor gene, CCR5, has a protective effect, according to a case–control study in Brazil with samples of 740 RA patients and 676 controls [ 25 ].…”

Section: Genetic Predisposition For Rheumatoid Arthritismentioning

confidence: 99%

Genetic Polymorphisms Associated with Rheumatoid Arthritis Development and Antirheumatic Therapy Response

Mikhaylenko

Немцова

Bure

et al. 2020

IJMS

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Rheumatoid arthritis (RA) is the most common inflammatory arthropathy worldwide. Possible manifestations of RA can be represented by a wide variability of symptoms, clinical forms, and course options. This multifactorial disease is triggered by a genetic predisposition and environmental factors. Both clinical and genealogical studies have demonstrated disease case accumulation in families. Revealing the impact of candidate gene missense variants on the disease course elucidates understanding of RA molecular pathogenesis. A multivariate genomewide association study (GWAS) based analysis identified the genes and signalling pathways involved in the pathogenesis of the disease. However, these identified RA candidate gene variants only explain 30% of familial disease cases. The genetic causes for a significant proportion of familial RA have not been determined until now. Therefore, it is important to identify RA risk groups in different populations, as well as the possible prognostic value of some genetic variants for disease development, progression, and treatment. Our review has two purposes. First, to summarise the data on RA candidate genes and the increased disease risk associated with these alleles in various populations. Second, to describe how the genetic variants can be used in the selection of drugs for the treatment of RA.

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Section: Genetic Predisposition For Rheumatoid Arthritismentioning

confidence: 99%

Genetic Polymorphisms Associated with Rheumatoid Arthritis Development and Antirheumatic Therapy Response

Mikhaylenko

Немцова

Bure

et al. 2020

IJMS

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“…CCR5 and its ligands C‐C motif ligand 3 (CCL3; also termed macrophage inflammatory protein [MIP]‐1α), CCL4 (MIP‐1β), CCL5 (regulated upon activation, normal T cell expressed and secreted [RANTES]), and CCL3L1 have been associated with exacerbation of chronic inflammatory and autoimmune diseases. Despite varying information due probably to ethnicity effects (Lee et al , ; Schauren et al , ), further complicated in admixed populations (Toson et al , ), epidemiological studies support the ccr5 Δ32 allele as a marker for good prognosis for these overreactive immune diseases (Vangelista & Vento, ). In contrast, ccr5 Δ32 homozygotes are prone to fatal infections by several pathogens such as influenza, West Nile, and tick‐borne encephalitis viruses (Lim & Murphy, ; Falcon et al , ; Ellwanger & Chies, ).…”

Section: Introductionmentioning

confidence: 99%

CCR 5 deficiency impairs CD 4 ⁺ T‐cell memory responses and antigenic sensitivity through increased ceramide synthesis

et al. 2020

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CCR5 is not only a coreceptor for HIV‐1 infection in CD4+ T cells, but also contributes to their functional fitness. Here, we show that by limiting transcription of specific ceramide synthases, CCR5 signaling reduces ceramide levels and thereby increases T‐cell antigen receptor (TCR) nanoclustering in antigen‐experienced mouse and human CD4+ T cells. This activity is CCR5‐specific and independent of CCR5 co‐stimulatory activity. CCR5‐deficient mice showed reduced production of high‐affinity class‐switched antibodies, but only after antigen rechallenge, which implies an impaired memory CD4+ T‐cell response. This study identifies a CCR5 function in the generation of CD4+ T‐cell memory responses and establishes an antigen‐independent mechanism that regulates TCR nanoclustering by altering specific lipid species.

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“…Rheumatoid arthritis is a systemic autoimmune disease characterized by progressive damage to the joints caused by chronic inflammation in the synovial fluid. Given the intense migration of immune cells to the inflammation sites, the role of CCR5 in rheumatoid arthritis appears to be of great importance (179,180). In Brazil, two studies investigating the role of the CCR5D32 variant in rheumatoid arthritis were published.…”

Section: Sickle Cell Disease (Scd)mentioning

confidence: 99%

CCR5Δ32 in Brazil: Impacts of a European Genetic Variant on a Highly Admixed Population

Kulmann-Leal

Ellwanger

2021

Front. Immunol.

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The genetic background of Brazilians encompasses Amerindian, African, and European components as a result of the colonization of an already Amerindian inhabited region by Europeans, associated to a massive influx of Africans. Other migratory flows introduced into the Brazilian population genetic components from Asia and the Middle East. Currently, Brazil has a highly admixed population and, therefore, the study of genetic factors in the context of health or disease in Brazil is a challenging and remarkably interesting subject. This phenomenon is exemplified by the genetic variant CCR5Δ32, a 32 base-pair deletion in the CCR5 gene. CCR5Δ32 originated in Europe, but the time of origin as well as the selective pressures that allowed the maintenance of this variant and the establishment of its current frequencies in the different human populations is still a field of debates. Due to its origin, the CCR5Δ32 allele frequency is high in European-derived populations (~10%) and low in Asian and African native human populations. In Brazil, the CCR5Δ32 allele frequency is intermediate (4-6%) and varies on the Brazilian States, depending on the migratory history of each region. CCR5 is a protein that regulates the activity of several immune cells, also acting as the main HIV-1 co-receptor. The CCR5 expression is influenced by CCR5Δ32 genotypes. No CCR5 expression is observed in CCR5Δ32 homozygous individuals. Thus, the CCR5Δ32 has particular effects on different diseases. At the population level, the effect that CCR5Δ32 has on European populations may be different than that observed in highly admixed populations. Besides less evident due to its low frequency in admixed groups, the effect of the CCR5Δ32 variant may be affected by other genetic traits. Understanding the effects of CCR5Δ32 on Brazilians is essential to predict the potential use of pharmacological CCR5 modulators in Brazil. Therefore, this study reviews the impacts of the CCR5Δ32 on the Brazilian population, considering infectious diseases, inflammatory conditions, and cancer. Finally, this article provides a general discussion concerning the impacts of a European-derived variant, the CCR5Δ32, on a highly admixed population.

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CCR5Δ32and the genetic susceptibility to rheumatoid arthritis in admixed populations: a multicentre study

Cited by 9 publications

References 8 publications

Genetic Polymorphisms Associated with Rheumatoid Arthritis Development and Antirheumatic Therapy Response

Genetic Polymorphisms Associated with Rheumatoid Arthritis Development and Antirheumatic Therapy Response

CCR 5 deficiency impairs CD 4 ⁺ T‐cell memory responses and antigenic sensitivity through increased ceramide synthesis

CCR5Δ32 in Brazil: Impacts of a European Genetic Variant on a Highly Admixed Population

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CCR5Δ32and the genetic susceptibility to rheumatoid arthritis in admixed populations: a multicentre study

Cited by 9 publications

References 8 publications

Genetic Polymorphisms Associated with Rheumatoid Arthritis Development and Antirheumatic Therapy Response

Genetic Polymorphisms Associated with Rheumatoid Arthritis Development and Antirheumatic Therapy Response

CCR 5 deficiency impairs CD 4 + T‐cell memory responses and antigenic sensitivity through increased ceramide synthesis

CCR5Δ32 in Brazil: Impacts of a European Genetic Variant on a Highly Admixed Population

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CCR 5 deficiency impairs CD 4 ⁺ T‐cell memory responses and antigenic sensitivity through increased ceramide synthesis