title: Common Variants in Cholesterol Synthesis- and Transport-Related Genes Associate with Circulating Cholesterol Responses to Intakes of Conventional Dairy Products in Healthy Individuals.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: Department of Human Nutritional Sciences and Richardson Centre for Functional Foods and Nutraceuticals, University of Manitoba, Winnipeg, Manitoba, Canada; and.
authors.forename: Mohammad Mh
authors.initials: MM
authors.lastname: Abdullah
authors.affiliation: Institute of Nutrition and Functional Foods, Laval University, Quebec City, Quebec, Canada.
authors.forename: Audrey
authors.initials: A
authors.lastname: Cyr
authors.affiliation: Institute of Nutrition and Functional Foods, Laval University, Quebec City, Quebec, Canada.
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Lépine
authors.affiliation: Department of Human Nutritional Sciences and Richardson Centre for Functional Foods and Nutraceuticals, University of Manitoba, Winnipeg, Manitoba, Canada; and.
authors.forename: Peter K
authors.initials: PK
authors.lastname: Eck
authors.affiliation: Institute of Nutrition and Functional Foods, Laval University, Quebec City, Quebec, Canada.
authors.forename: Patrick
authors.initials: P
authors.lastname: Couture
authors.affiliation: Institute of Nutrition and Functional Foods, Laval University, Quebec City, Quebec, Canada.
authors.forename: Benoît
authors.initials: B
authors.lastname: Lamarche
authors.affiliation: Department of Human Nutritional Sciences and Richardson Centre for Functional Foods and Nutraceuticals, University of Manitoba, Winnipeg, Manitoba, Canada; and peter_jones@umanitoba.ca.
authors.forename: Peter Jh
authors.initials: PJ
authors.lastname: Jones
mesh_terms: D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5 / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D002784:Cholesterol / Q000097:blood*; D002790:Cholesterol 7-alpha-Hydroxylase / Q000235:genetics*; D008078:Cholesterol, LDL / Q000097:blood; D003611:Dairy Products; D004032:Diet; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D050155:Lipogenesis / Q000235:genetics; D008074:Lipoproteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000235:genetics*; D055815:Young Adult
chemical_list: C416945:ABCG5 protein, human; D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D008078:Cholesterol, LDL; D008074:Lipoproteins; D002784:Cholesterol; C553219:CYP7A1 protein, human; D002790:Cholesterol 7-alpha-Hydroxylase; D044925:Oxidoreductases Acting on CH-CH Group Donors; C019995:7-dehydrocholesterol reductase
keywords: cardiovascular disease; cholesterol; dairy; gene-diet interaction; genotype