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Effect of race, genetic population structure, and genetic models in two-locus association studies: clustering of functional renin-angiotensin system gene variants in hypertension association studies
Pereira, A. C; Mota, G. A; Benseñor, I; Lotufo, P. A; Krieger, J. E.
  • Pereira, A. C; Universidade de Säo Paulo. Faculdade de Medicina. Instituto do Coraçäo. Laboratório de Genética e Cardiologia Molecular. Säo Paulo. BR
  • Mota, G. A; Universidade de Säo Paulo. Faculdade de Medicina. Instituto do Coraçäo. Laboratório de Genética e Cardiologia Molecular. Säo Paulo. BR
  • Benseñor, I; Universidade de Säo Paulo. Faculdade de Medicina. Departamento de Clínica Médica. Säo Paulo. BR
  • Lotufo, P. A; Universidade de Säo Paulo. Faculdade de Medicina. Departamento de Clínica Médica. Säo Paulo. BR
  • Krieger, J. E; Universidade de Säo Paulo. Faculdade de Medicina. Instituto do Coraçäo. Laboratório de Genética e Cardiologia Molecular. Säo Paulo. BR
Braz. j. med. biol. res ; 34(11): 1421-1428, Nov. 2001. ilus, tab
Article Dans Anglais | LILACS | ID: lil-303317
ABSTRACT
Previous genetic association studies have overlooked the potential for biased results when analyzing different population structures in ethnically diverse populations. The purpose of the present study was to quantify this bias in two-locus association studies conducted on an admixtured urban population. We studied the genetic structure distribution of angiotensin-converting enzyme insertion/deletion (ACE I/D) and angiotensinogen methionine/threonine (M/T) polymorphisms in 382 subjects from three subgroups in a highly admixtured urban population. Group I included 150 white subjects; group II, 142 mulatto subjects, and group III, 90 black subjects. We conducted sample size simulation studies using these data in different genetic models of gene action and interaction and used genetic distance calculation algorithms to help determine the population structure for the studied loci. Our results showed a statistically different population structure distribution of both ACE I/D (P = 0.02, OR = 1.56, 95 percent CI = 1.05-2.33 for the D allele, white versus black subgroup) and angiotensinogen M/T polymorphism (P = 0.007, OR = 1.71, 95 percent CI = 1.14-2.58 for the T allele, white versus black subgroup). Different sample sizes are predicted to be determinant of the power to detect a given genotypic association with a particular phenotype when conducting two-locus association studies in admixtured populations. In addition, the postulated genetic model is also a major determinant of the power to detect any association in a given sample size. The present simulation study helped to demonstrate the complex interrelation among ethnicity, power of the association, and the postulated genetic model of action of a particular allele in the context of clustering studies. This information is essential for the correct planning and interpretation of future association studies conducted on this population
Sujets)
Texte intégral: Disponible Indice: LILAS (Amériques) Sujet Principal: Polymorphisme génétique / Système rénine-angiotensine / / Hypertension artérielle Type d'étude: Étude pronostique / Facteurs de risque Limites du sujet: Femelle / Humains / Mâle langue: Anglais Texte intégral: Braz. j. med. biol. res Thème du journal: Biologie / Médicament Année: 2001 Type: Article Pays d'affiliation: Brésil Institution/Pays d'affiliation: Universidade de Säo Paulo/BR

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Texte intégral: Disponible Indice: LILAS (Amériques) Sujet Principal: Polymorphisme génétique / Système rénine-angiotensine / / Hypertension artérielle Type d'étude: Étude pronostique / Facteurs de risque Limites du sujet: Femelle / Humains / Mâle langue: Anglais Texte intégral: Braz. j. med. biol. res Thème du journal: Biologie / Médicament Année: 2001 Type: Article Pays d'affiliation: Brésil Institution/Pays d'affiliation: Universidade de Säo Paulo/BR