Location: Boston, MassachusettsTitle: The effects of ABCG5/G8 polymorphisms on HDL-cholesterol concentrations depend on ABCA1 genetic variants in the Boston Puerto Rican health study) Author
|Tucker, Katherine L.|
|Smith, Caren E.|
|Lane, Jacqueline M.|
|Lai, Chao Qiang|
|Ordovas, Jose M.|
Submitted to: Nutrition Metabolism and Cardiovascular Disease
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/6/2009
Publication Date: 10/1/2010
Citation: Junyent, M., Tucker, K., Smith, C., Lane, J., Mattei, J., Lai, C., Parnell, L.D., Ordovas, J. 2010. The effects of ABCG5/G8 polymorphisms on HDL-cholesterol concentrations depend on ABCA1 genetic variants in the Boston Puerto Rican health study. Nutrition Metabolism and Cardiovascular Disease. 20(8):558-566. Interpretive Summary: Blood lipoprotein levels are major risk factors for cardiovascular diseases. Among the three major circulating lipoproteins, LDL, HDL and VLDL, the first (LDL) is the best characterized and most dietary messages are aimed o reduce its levels in plasma. Less is known about the metabolism of HDL in part because its metabolism is much more complex. A number of enzymes and receptors have been found to be involved in defining blood HDL concentrations. Among them we have some members of a family of transporters (ATP-binding cassette transporters) more specifically those known as ABCA1, ABCG5 and ABCG8. To investigate the effect of genetic polymorphisms at these genes on HDL levels we genotyped some of the known variants in 788 Hispanic subjects (228 men and 560 women) who participated in the Boston Puerto Rican Health Study. We found significant cross-talk between ABCG8 and ABCA1 polymorphisms suggesting that is the combination of polymorphisms at several related genes what really impacts on HDL levels. Therefore, this knowledge contributes to our knowledge of HDL metabolism and helps to define the path of action to modify, using dietary approaches, this important cardiovascular risk factor.
Technical Abstract: Background and aims: 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 (i7892 T > C, 5U145A > C, T54CA > G, T400KC > A) and ABCA1 (i27943 G > A, i48168 G > A,K219RG > A, i125970 G > C, 3U8995A > G) genes with HDL-C concentrations. Methods and 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 geneegene interactions for HDL-C were found between ABCG8 (5U145A > C, T54CA > G, T400KC > A) SNPs and ABCA1_i48168 G > A genetic variant (PZ0.009, PZ0.042 and PZ0.036, 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 400 K allele at ABCG8 SNPs, only if they were also homozygous for the minor allele (A) at the aforementioned ABCA1 SNP. Conclusions: The geneegene 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.