title: The effects of ABCG5/G8 polymorphisms on HDL-cholesterol concentrations depend on ABCA1 genetic variants in the Boston Puerto Rican Health Study.
abstract: OBJECTIVE
  ATP-binding cassette transporters G5/G8 (ABCG5/G8) are associated with HDL-C concentrations. To assess whether the effect of ABCG5/G8 genetic variants on HDL-C concentrations is dependent on ATP-binding cassette transporters A1 (ABCA1), we studied potential interactions between single nucleotide polymorphisms (SNPs) at ABCG5/G8 (i7892T > C, 5U145A > C, T54CA > G, T400KC > A) and ABCA1 (i27943G > A, i48168G > A, K219RG > A, i125970G > C, 3U8995A > G) genes with HDL-C concentrations.
  
  
  RESULTS
  ABCG5/G8 and ABCA1 SNPs were genotyped in 788 subjects (228 men and 560 women) who participated in the Boston Puerto Rican Health Study. Biochemical measurements were determined by standard procedures. Genotyping was performed using TaqMan assays according to routine laboratory protocols. Significant gene-gene interactions for HDL-C were found between ABCG8 (5U145A > C, T54CA > G, T400KC > A) SNPs and ABCA1_i48168G > A genetic variant (P = 0.009, P = 0.042 and P = 0.036, respectively), in which carriers of the 5U145C and 54C alleles, and homozygotes for the T400 allele at ABCG8 genetic variants displayed lower HDL-C concentrations than homozygotes for the 5U145A and T54 alleles, and heterozygotes for the 400K allele at ABCG8 SNPs, only if they were also homozygous for the minor allele (A) at the aforementioned ABCA1 SNP.
  
  
  CONCLUSIONS
  The gene-gene interactions reported in the present study support the hypothesis that the effect of ABCG5/G8 genetic variants on HDL-C concentrations is dependent on ABCA1 expression. Replication of these analyses to further populations, particularly with low HDL-C, is clearly warranted.
authors.affiliation: The Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging, Tufts University School of Medicine, Boston, MA 02111, USA. mireia.junyent@tufts.edu
authors.forename: M
authors.initials: M
authors.lastname: Junyent
authors.forename: K L
authors.initials: KL
authors.lastname: Tucker
authors.forename: C E
authors.initials: CE
authors.lastname: Smith
authors.forename: J M
authors.initials: JM
authors.lastname: Lane
authors.forename: J
authors.initials: J
authors.lastname: Mattei
authors.forename: C Q
authors.initials: CQ
authors.lastname: Lai
authors.forename: L D
authors.initials: LD
authors.lastname: Parnell
authors.forename: J M
authors.initials: JM
authors.lastname: Ordovas
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000368:Aged; D001900:Boston; D008076:Cholesterol, HDL / Q000097:blood*; D004843:Epistasis, Genetic; D005260:Female; D006630:Hispanic or Latino / Q000235:genetics*; D006801:Humans; D008074:Lipoproteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: C577836:ABCA1 protein, human; C416945:ABCG5 protein, human; C416946:ABCG8 protein, human; D064286:ATP Binding Cassette Transporter 1; D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters; D008076:Cholesterol, HDL; D008074:Lipoproteins
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