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Polymorphisms of ATP binding cassette G5 and G8 transporters: their effect on cholesterol metabolism after moderate weight loss in overweight and obese hyperlipidemic women
Author(s) -
Santosa Sylvia,
Demonty Isabelle,
Lichtenstein Alice H,
Ordovas Jose,
Jones Peter JH
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a861
Subject(s) - single nucleotide polymorphism , medicine , endocrinology , cholesterol , weight loss , overweight , lipid metabolism , genotype , biology , obesity , chemistry , biochemistry , gene
Objective To determine the effect of polymorphisms ABCG5 and ABCG8 transporters on changes in lipid levels, cholesterol absorption rate (ABS), fractional synthesis rate (FSR), and turnover (TO) after moderate weight loss (WL) in women. Design Cholesterol metabolism was measured pre and post WL in 35 hyperlipidemic women (BMI 28–39 kg/m 2 ) 35–60 yr after a 6 mo weight loss trial. ABS was measured using the dual isotope ratio method, FSR by D 7 labelled water incorporation, and TO by D 7 cholesterol decay. Single nucleotide polymorphisms (SNP) C1950G, I18429 , I7892, and M216 on ABCG5, and C54Y, D19H, I14222 , and T400K on ABCG8 were determined using PCR‐based TaqMan allele discrimination assays Results Mean WL was 11.7±2.5 kg ( P< 0.0001). ABS changes were related to C1950G SNP. Individuals with the G/G genotype had significantly decreased (16.9%±3.0%), whereas individuals with the C/C and C/G genotypes had increased (4.4%±13.2% and 5.5%±13.7%, respectively) rates of ABS in response to WL. Absolute WL was similar among C1950G genotypes. There was no effect of ABCG5 or ABCG8 SNPs on changes in lipid level after WL. Changes in ABS, FSR and TO after WL were similar among other SNPs. Conclusion C1950G SNP on ABCG5 may predict individuals who would benefit from therapies that alter rates of cholesterol absorption. *This project was funded by CIHR. SS was funded by NSERC.