Please use this identifier to cite or link to this item: http://ds.saudeindigena.icict.fiocruz.br/handle/bvs/6776
Title: A functional ABCA1 gene variant is associated with low HDL-cholesterol levels and shows evidence of positive selection in Native Americans
Authors: Acuña-Alonzo, Víctor
Flores-Dorantes, Teresa
Kruit, Janine K.
Villarreal-Molina, Teresa
Arellano-Campos, Olimpia
Hünemeier, Tábita
Moreno-Estrada, Andrés
Ortiz-López, Ma Guadalupe
Villamil-Ramírez, Hugo
León-Mimila, Paola
Villalobos-Comparan, Marisela
Jacobo-Albavera, Leonor
Ramírez-Jiménez, Salvador
Sikora, Martin
Zhang, Lin-Hua
Pape, Terry D.
Granados-Silvestre, Ma de Angeles
Montufar-Robles, Isela
Tito-Alvarez, Ana M.
Zurita-Salinas, Camilo
Bustos-Arriaga, José
Cedillo-Barrón, Leticia
Gómez-Trejo, Celta
Barquera-Lozano, Rodrigo
Vieira Filho, João Paulo B.
Granados, Julio
Romero-Hidalgo, Sandra
Huertas-Vázquez, Adriana
González-Martín, Antonio
Gorostiza, Amaya
Bonatto, Sandro L.
Rodríguez-Cruz, Maricela
Wang, Li
Tusié-Luna, Teresa
Aguilar-Salinas, Carlos A.
Lisker, Ruben
Moises, Regina S.
Menjivar, Marta
Salzano, Francisco M.
Knowler, William C.
Bortolini, M. Cátira
Hayden, Michael R.
Baier, Leslie J.
Canizales-Quinteros, Samuel
Abstract: It has been suggested that the higher susceptibility of Hispanics to metabolic disease is related to their Native American heritage. A frequent cholesterol transporter ABCA1 (ATP-binding cassette transporter A1) gene variant (R230C, rs9282541) apparently exclusive to Native American individuals was associated with low high-density lipoprotein cholesterol (HDL-C) levels, obesity and type 2 diabetes in Mexican Mestizos. We performed a more extensive analysis of this variant in 4405 Native Americans and 863 individuals from other ethnic groups to investigate genetic evidence of positive selection, to assess its functional effect in vitro and to explore associations with HDL-C levels and other metabolic traits. The C230 allele was found in 29 of 36 Native American groups, but not in European, Asian or African individuals. C230 was observed on a single haplotype, and C230-bearing chromosomes showed longer relative haplotype extension compared with other haplotypes in the Americas. Additionally, single-nucleotide polymorphism data from the Human Genome Diversity Panel Native American populations were enriched in significant integrated haplotype score values in the region upstream of the ABCA1 gene. Cells expressing the C230 allele showed a 27% cholesterol efflux reduction (P< 0.001), confirming this variant has a functional effect in vitro. Moreover, the C230 allele was associated with lower HDL-C levels (P = 1.77 x 10(-11)) and with higher body mass index (P = 0.0001) in the combined analysis of Native American populations. This is the first report of a common functional variant exclusive to Native American and descent populations, which is a major determinant of HDL-C levels and may have contributed to the adaptive evolution of Native American populations.
Keywords: Health of Indigenous Peoples
Cholesterol, HDL / blood
Cholesterol, HDL / genetics
Gene Frequency
ATP Binding Cassette Transporter 1
ATP-Binding Cassette Transporters / genetics
Alleles
Genome-Wide Association Study
Haplotypes
Linkage Disequilibrium
Selection, Genetic
Keywords: Saúde de Populações Indígenas
Epidemiologia
Estudos Epidemiológicos
Genética Humana
Doenças Crônicas não Transmissíveis
Índios Latino-Americanos
DeCS: Saúde de Populações Indígenas
Seleção Genética
Alelos
Transportador 1 de Cassete de Ligação de ATP / genética
Transportador 1 de Cassete de Ligação de ATP/ fisiologia
HDL-Colesterol / sangue
HDL-Colesterol / genética
Estudo de Associação Genômica Ampla
Haplótipos
Issue Date: 2010
Publisher: Oxford University Press
Citation: ACUÑA-ALONZO, Víctor; et al. A functional ABCA1 gene variant is associated with low HDL-cholesterol levels and shows evidence of positive selection in Native Americans. Human Molecular Genetics, v. 19, n. 14, p. 2877-2885, 2010.
metadata.dc.identifier.doi: 10.1093/hmg/ddq173
ISSN: 1460-2083
Other Identifiers: 10.1093/hmg/ddq173
1460-2083
Copyright: open access
Appears in Collections:GH - Artigos de Periódicos



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