title: Interaction between a variant of CDKN2A/B-gene with lifestyle factors in determining dyslipidemia and estimated cardiovascular risk: A step toward personalized nutrition.
abstract: Several genome-wide-association-studies have identified genetic variants in a region on chromosome 9p21 that are associated with an increased risk of Cardiovascular disease (CVD) and diabetes. Here we have explored the interaction of a genetic variant of the CDKN2A/B-rs10811661 gene locus with cardiovascular risk factors and environmental-exposures (e.g., diet and physical activity) in 1165 individuals recruited from the Mashhad-Stroke and Heart-Atherosclerotic-Disorders cohort.
  
  
  
  Genotyping was carried out using TaqMan-real-time-PCR based method. The association of CDKN2A/B-rs10811661 locus and its interaction with dietary intake in association with the main determinants of dyslipidemia, and cardiovascular-risk-factors were assessed in 2 cohorts.
  
  
  
  Our data showed that obese subjects with a TT genotype had a higher level of TG, TG/HDL ratio and Hs-CRP, compared to the subjects with the wild type genotype, or individuals with a normal BMI. Moreover, the presence of a TT genotype was associated with increased risk of hypercholesterolemia, insulin resistance and CVD. These effects were more pronounced in the sub-group with low physical activity and a high dietary energy intake (e.g., the interaction between TT genotype and total energy intake on serum cholesterol was positive (RERI: 0.2, 95%CI (-0.96-1.3), AP: 0.1, 95%CI (-0.5-0.7) and SI: 1.2, 95%CI (0.3-5.1))).
  
  
  
  We have found a significant association between the CDKN2A-rs10811661 polymorphism with cardiovascular risk factors and dyslipidemia in a non-diabetic population. It is possible that a low energy diet and high physical activity could ameliorate the unfavorable effects of T allele of CDKN2A/B locus. Functional analysis is warranted to investigate the value of this genetic biomarker of CVD risk in obese people.
authors.affiliation: Molecular Medicine Group, Department of Modern Sciences and Technologies, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Mehrane
authors.initials: M
authors.lastname: Mehramiz
authors.affiliation: Molecular Medicine Group, Department of Modern Sciences and Technologies, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Biotechnology, Faculty of Medicine, Arak University of Medical Sciences, Arak, Iran.
authors.forename: Faeze
authors.initials: F
authors.lastname: Ghasemi
authors.affiliation: Department of Biostatistics & Epidemiology, School of Health, Management & Social Determinants of Health Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Habibollah
authors.initials: H
authors.lastname: Esmaily
authors.affiliation: Molecular Medicine Group, Department of Modern Sciences and Technologies, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Tayefi
authors.affiliation: Department of Medical Biochemistry, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Microanatomy Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Metabolic Syndrome Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Seyed Mahdi
authors.initials: SM
authors.lastname: Hassanian
authors.affiliation: Molecular Medicine Group, Department of Modern Sciences and Technologies, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Mahsa
authors.initials: M
authors.lastname: Sadeghzade
authors.affiliation: Molecular Medicine Group, Department of Modern Sciences and Technologies, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Sadabadi
authors.affiliation: Cardiovascular Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Moohebati
authors.affiliation: Cardiovascular Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Mahmoud Reza
authors.initials: MR
authors.lastname: Azarpazhooh
authors.affiliation: Metabolic Syndrome Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Seyed Mohammad Reza
authors.initials: SMR
authors.lastname: Parizadeh
authors.affiliation: Cardiovascular Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Alireza
authors.initials: A
authors.lastname: Heidari-Bakavoli
authors.affiliation: Biochemistry of Nutrition Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Safarian
authors.affiliation: Biochemistry of Nutrition Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Nematy
authors.affiliation: Cardiovascular Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Ebrahimi
authors.affiliation: Department of Molecular Microbiology and Immunology, St. Louis University School of Medicine, Saint Louis, MO, USA.
authors.forename: Mikhail
authors.initials: M
authors.lastname: Ryzhikov
authors.affiliation: Brighton & Sussex Medical School, Division of Medical Education, Falmer, Brighton, Sussex BN1 9PH, UK.
authors.forename: Gordon A
authors.initials: GA
authors.lastname: Ferns
authors.affiliation: Metabolic Syndrome Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: ghayourm@mums.ac.ir.
authors.forename: Majid
authors.initials: M
authors.lastname: Ghayour-Mobarhan
authors.affiliation: Metabolic Syndrome Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: avana@mums.ac.ir.
authors.forename: Amir
authors.initials: A
authors.lastname: Avan
mesh_terms: D001794:Blood Pressure; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000235:genetics / Q000517:prevention & control; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D004032:Diet / Q000706:statistics & numerical data*; D050171:Dyslipidemias / Q000453:epidemiology / Q000235:genetics / Q000517:prevention & control; D015444:Exercise; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008019:Life Style; D008055:Lipids / Q000097:blood; D008297:Male; D052756:Nutritional Sciences; D057285:Precision Medicine; D012307:Risk Factors
chemical_list: C000614131:CDKN2A protein, human; C493966:CDKN2B protein, human; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D008055:Lipids
keywords: CDKN2A/B; Coronary artery disease; Dietary intake; Physical activity