BACKGROUND: While involvement of ABCB1 is well known in drug transport, its metabolite transport role is not so well understood. Like other ABC transporters, ABCB1 might be implicated in cholesterol homeostasis and ABCB1 polymorphisms which are responsible for drug resistance might affect lipid homeostasis. Our objective was thus to investigate the implication of ABCB1 polymorphisms and haplotypes in the genetic variability of lipid constituents in healthy people. METHODS: T-129C, G-1A, A61G, G1199A, C1236T, T-76A, G2677T/A and C3435T polymorphisms were genotyped in 371 supposed healthy individuals from the STANISLAS cohort. Each polymorphism was tested with plasma concentrations of total cholesterol, HDL and LDL cholesterol, triglycerides and apolipoproteins A1, B, C3 and E. RESULTS: After adjustment for covariates, carriers of at least one 3435T allele had a significant higher level of apolipoprotein A1 (p = 0.005). In addition, significant correlations were observed in a sex-dependent manner. Women carrying either T-76 or 1236T allele (tendency with G-1 and 2677T/A) had lower total cholesterol (p < or = 0.01) and apolipoprotein B (T-76 exclusively, p=0.002). Haplotypes analysis was not more informative than the single polymorphisms except G2677T/A-C3435T haplotypes for apolipoprotein A1 concentration. CONCLUSION: ABCB1 polymorphisms contribute to the genetic variability of plasma values of lipids and lipoproteins in healthy people.
BACKGROUND: While involvement of ABCB1 is well known in drug transport, its metabolite transport role is not so well understood. Like other ABC transporters, ABCB1 might be implicated in cholesterol homeostasis and ABCB1 polymorphisms which are responsible for drug resistance might affect lipid homeostasis. Our objective was thus to investigate the implication of ABCB1 polymorphisms and haplotypes in the genetic variability of lipid constituents in healthy people. METHODS:T-129C, G-1A, A61G, G1199A, C1236T, T-76A, G2677T/A and C3435T polymorphisms were genotyped in 371 supposed healthy individuals from the STANISLAS cohort. Each polymorphism was tested with plasma concentrations of total cholesterol, HDL and LDL cholesterol, triglycerides and apolipoproteins A1, B, C3 and E. RESULTS: After adjustment for covariates, carriers of at least one 3435T allele had a significant higher level of apolipoprotein A1 (p = 0.005). In addition, significant correlations were observed in a sex-dependent manner. Women carrying either T-76 or 1236T allele (tendency with G-1 and 2677T/A) had lower total cholesterol (p < or = 0.01) and apolipoprotein B (T-76 exclusively, p=0.002). Haplotypes analysis was not more informative than the single polymorphisms except G2677T/A-C3435T haplotypes for apolipoprotein A1 concentration. CONCLUSION:ABCB1 polymorphisms contribute to the genetic variability of plasma values of lipids and lipoproteins in healthy people.
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