title: The ABCA1 gene R230C variant is associated with decreased risk of premature coronary artery disease: the genetics of atherosclerotic disease (GEA) study.
abstract: BACKGROUND
  ABCA1 genetic variation is known to play a role in HDL-C levels and various studies have also implicated ABCA1 variation in cardiovascular risk. The functional ABCA1/R230C variant is frequent in the Mexican population and has been consistently associated with low HDL-C concentrations. Although it has been associated with other cardiovascular risk factors such as obesity and type 2 diabetes mellitus, it is not known whether it is associated with coronary artery disease (CAD).
  
  
  OBJECTIVE
  The purpose of the study was to analyze whether the ABCA1/R230C variant is associated with premature CAD in a case-control association study (GEA or Genetics of Atherosclerotic Disease), and to explore whether BMI modulates the effect of the C230 allele on other metabolic traits using a population-based design.
  
  
  RESULTS
  The C230 allele was significantly associated with both lower HDL-C levels and a lower risk of premature CAD as compared to controls (OR = 0.566; P(add) = 1.499×10(-5)). In addition, BMI modulated the effect of R230C on body fat distribution, as the correlation between BMI and visceral to subcutaneous adipose tissue (a metric of the propensity to store fat viscerally as compared to subcutaneously) was negative in RR homozygous individuals, but positive in premenopausal women bearing the C230 allele, with a statistically significant interaction (P = 0.005). BMI-R230C interaction was also significant for triglyceride levels in women regardless of their menopausal status (P = 0.036).
  
  
  CONCLUSIONS
  This is the first study assessing the effect of the R230C/ABCA1 variant in remature CAD. C230 was associated with both decreased HDL-C levels and a lower risk of premature CAD, and gender-specific BMI-R230C interactions were observed for different metabolic traits. These interactions may help explain inconsistencies in associations, and underscore the need to further analyze interactions of this functional and frequent variant with diet, exercise and other environmental factors.
authors.affiliation: Laboratorio de Genómica de Enfermedades Cardiovasculares, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City, Mexico. mvillareal@inmegen.gob.mx
authors.forename: Teresa
authors.initials: T
authors.lastname: Villarreal-Molina
authors.forename: Carlos
authors.initials: C
authors.lastname: Posadas-Romero
authors.forename: Sandra
authors.initials: S
authors.lastname: Romero-Hidalgo
authors.forename: Erika
authors.initials: E
authors.lastname: Antúnez-Argüelles
authors.forename: Araceli
authors.initials: A
authors.lastname: Bautista-Grande
authors.forename: Gilberto
authors.initials: G
authors.lastname: Vargas-Alarcón
authors.forename: Eric
authors.initials: E
authors.lastname: Kimura-Hayama
authors.forename: Samuel
authors.initials: S
authors.lastname: Canizales-Quinteros
authors.forename: Juan Gabriel
authors.initials: JG
authors.lastname: Juárez-Rojas
authors.forename: Rosalinda
authors.initials: R
authors.lastname: Posadas-Sánchez
authors.forename: Guillermo
authors.initials: G
authors.lastname: Cardoso-Saldaña
authors.forename: Aída
authors.initials: A
authors.lastname: Medina-Urrutia
authors.forename: María Del Carmen
authors.initials: Mdel C
authors.lastname: González-Salazar
authors.forename: Rocío
authors.initials: R
authors.lastname: Martínez-Alvarado
authors.forename: Esteban
authors.initials: E
authors.lastname: Jorge-Galarza
authors.forename: Alessandra
authors.initials: A
authors.lastname: Carnevale
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000273:Adipose Tissue / Q000378:metabolism; D019943:Amino Acid Substitution / Q000235:genetics*; D050197:Atherosclerosis / Q000235:genetics*; D015992:Body Mass Index; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000235:genetics* / Q000378:metabolism; D003710:Demography; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017697:Premenopause / Q000235:genetics; D012307:Risk Factors
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters