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Common Variants in Cholesterol Synthesis– and Transport–Related Genes Associate with Circulating Cholesterol Responses to Intakes of Conventional Dairy Products in Healthy Individuals
- Source :
- The Journal of Nutrition. 146:1008-1016
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
Abstract
- Background Dairy intake has been associated with varying impacts on circulating cholesterol concentrations across nutritional epidemiology and intervention studies, with findings attributed mainly to differences in the nature of dairy products consumed or study designs. The contribution of the genomic architecture to such observations has yet to be revealed. Objective We assessed the impact of multiple common genetic variations in cholesterol-related genes on responses of serum cholesterol to the recommended amount of dairy product intake in Canada. Methods In a multicenter, randomized crossover design, 101 normolipidemic adults (n = 29 men and 72 women), with a mean ± SD age of 41.7 ± 16.7 y and a body mass index (BMI, in kg/m(2)) of 25.9 ± 4.3 consumed 3 servings/d of dairy [375 mL 1% milk-fat (MF) milk, 175 g 1.5% MF yogurt, and 30 g of 34% MF cheese] or energy-matched control products (juice, cashews, and cookies) provided within a prudent background diet for 4 wk each, separated by a 4- to 8-wk washout period. Serum lipid variables were determined by standard enzymatic methods by using an autoanalyzer. Candidate single nucleotide polymorphisms were assessed by TaqMan genotyping assay. Results The responsiveness of serum total cholesterol (TC) and LDL cholesterol to the dairy compared with the control diet was associated with individuals' genotypes. The cholesterol transport gene ATP-binding cassette subfamily G, member 5 (ABCG5) rs6720173-GG homozygotes had higher concentrations of TC (+0.18 mmol/L; P = 0.0118) and LDL cholesterol (+0.17 mmol/L; P = 0.0056) relative to C-allele carriers (-0.07 and -0.06 mmol/L, respectively). The bile acid synthesis gene cholesterol 7α-hydroxylase (CYP7A1) rs3808607-G-allele carriers had higher TC (+0.20 to +0.28 mmol/L; P = 0.0026) and LDL cholesterol (+0.19 mmol/L for GT genotype; P = 0.0260) relative to TT homozygotes (-0.11 and -0.03 mmol/L, respectively). In addition, the cholesterol synthesis gene 7-dehydrocholesterol reductase (DHCR7) rs760241-A-allele carriers had higher LDL cholesterol (+0.26 mmol/L; P = 0.0399) relative to GG homozygotes (+0.06 mmol/L). Conclusion Genetic variations in ABCG5, CYP7A1, and DHCR7 may contribute to differing responses of serum cholesterol to dairy intake among healthy adults. This trial was registered at clinicaltrials.gov as NCT01444326.
- Subjects :
- Adult
Male
0301 basic medicine
Oxidoreductases Acting on CH-CH Group Donors
medicine.medical_specialty
Adolescent
Genotype
Lipoproteins
Medicine (miscellaneous)
Single-nucleotide polymorphism
030204 cardiovascular system & hematology
Reductase
Biology
Cholesterol 7 alpha-hydroxylase
AutoAnalyzer
Young Adult
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Internal medicine
medicine
Humans
ATP Binding Cassette Transporter, Subfamily G, Member 5
Cholesterol 7-alpha-Hydroxylase
Aged
030109 nutrition & dietetics
Nutrition and Dietetics
Cholesterol
Lipogenesis
Genetic Variation
Cholesterol, LDL
Middle Aged
Crossover study
Diet
Endocrinology
Biochemistry
chemistry
ABCG5
biology.protein
Female
Dairy Products
Body mass index
Subjects
Details
- ISSN :
- 00223166
- Volume :
- 146
- Database :
- OpenAIRE
- Journal :
- The Journal of Nutrition
- Accession number :
- edsair.doi.dedup.....49b8f446d6416f1ceb9cab1ebd7e5ca1