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The CCR5?32 (rs333) polymorphism is not a predisposing factor for severe pandemic influenza in the Brazilian admixed population.

ABSTRACT: Recent studies have tried to identify host genetic variants that could explain severe cases and deaths in infection with Influenza A(H1N1)pdm09, especially among children and young adults. CCR5 is a chemokine receptor expressed on T cells, macrophages and dendritic cells, which is an important mediator of leukocyte chemotaxis during the immune response. A deletion mutation (?32) in this gene interferes with the response of immune cells, impairing viral clearance. We evaluated the CCR5?32 polymorphism (rs333) in individuals of the Brazilian admixed population with a diagnosis of Influenza A(H1N1)pdm09 infection.A total of 330 subjects with a diagnosis of Influenza A(H1N1)pdm09, evaluated at health services in the northern and northeastern regions of Brazil between June 2009 and August 2010, were genotyped for the ?32 deletion (rs333). The cases were classified according to the progression of infection into a group of hospitalized patients (n = 156) and a group of non-hospitalized patients (n = 174).No significant differences in the allele or genotype frequencies of the CCR5?32 polymorphism were observed between non-hospitalized and hospitalized patients (p = 0.289 and p = 0.431, respectively).The ?32 deletion in the CCR5 gene is not associated with an unfavorable outcome in patients infected with Influenza A(H1N1)pdm09 in the Brazilian admixed population.

SUBMITTER: Maestri A

PROVIDER: S-EPMC4520097 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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The CCR5Δ32 (rs333) polymorphism is not a predisposing factor for severe pandemic influenza in the Brazilian admixed population.

Maestri Alvino A dos Santos Mirleide Cordeiro MC Ribeiro-Rodrigues Elzemar M EM de Mello Wyller Alencar WA Sousa Rita Catarina Medeiros RC dos Santos Sidney Emanuel SE Sortica Vinicius Albuquerque VA

BMC research notes 20150730

<h4>Background</h4>Recent studies have tried to identify host genetic variants that could explain severe cases and deaths in infection with Influenza A(H1N1)pdm09, especially among children and young adults. CCR5 is a chemokine receptor expressed on T cells, macrophages and dendritic cells, which is an important mediator of leukocyte chemotaxis during the immune response. A deletion mutation (Δ32) in this gene interferes with the response of immune cells, impairing viral clearance. We evaluated ...[more]

PMID: 26223981

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Project description: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.

Dataset Information

The CCR5?32 (rs333) polymorphism is not a predisposing factor for severe pandemic influenza in the Brazilian admixed population.

Publications

The CCR5Δ32 (rs333) polymorphism is not a predisposing factor for severe pandemic influenza in the Brazilian admixed population.

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