title: CRY1 circadian gene variant interacts with carbohydrate intake for insulin resistance in two independent populations: Mediterranean and North American.
abstract: Dysregulation in the circadian system induced by variants of clock genes has been associated with type 2 diabetes. Evidence for the role of cryptochromes, core components of the system, in regulating glucose homeostasis is not supported by CRY1 candidate gene association studies for diabetes and insulin resistance in human, suggesting possible dietary influences. The purpose of this study was to test for interactions between a CRY1 polymorphism, rs2287161, and carbohydrate intake on insulin resistance in two independent populations: a Mediterranean (n = 728) and an European origin North American population (n = 820). Linear regression interaction models were performed in two populations to test for gene-diet interactions on fasting insulin and glucose and two insulin-related traits, homeostasis model assessment of insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI). In addition, fixed effects meta-analyses for these interactions were performed. Cohort-specific interaction analyses showed significant interactions between the CRY1 variant and dietary carbohydrates for insulin resistance in both populations (p < 0.05). Findings from the meta-analyses of carbohydrate-single nucleotide polymorphism interactions indicated that an increase in carbohydrate intake (% of energy intake) was associated with a significant increase in HOMA-IR (p = 0.011), fasting insulin (p = 0.007) and a decrease in QUICKI (p = 0.028), only among individuals homozygous for the minor C allele. This novel finding supports the link between the circadian system and glucose metabolism and suggests the importance this CRY1 locus in developing personalized nutrition programs aimed at reducing insulin resistance and diabetes risk.
authors.affiliation: Nutrition and Genomics Laboratory, Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging, Tufts University , Boston, MA , USA .
authors.forename: Hassan S
authors.initials: HS
authors.lastname: Dashti
authors.forename: Caren E
authors.initials: CE
authors.lastname: Smith
authors.forename: Yu-Chi
authors.initials: YC
authors.lastname: Lee
authors.forename: Laurence D
authors.initials: LD
authors.lastname: Parnell
authors.forename: Chao-Qiang
authors.initials: CQ
authors.lastname: Lai
authors.forename: Donna K
authors.initials: DK
authors.lastname: Arnett
authors.forename: José M
authors.initials: JM
authors.lastname: Ordovás
authors.forename: Marta
authors.initials: M
authors.lastname: Garaulet
mesh_terms: D000328:Adult; D000407:Alabama / Q000453:epidemiology; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D002940:Circadian Rhythm / Q000235:genetics*; D056931:Cryptochromes / Q000235:genetics*; D004032:Diet / Q000208:ethnology; D004040:Dietary Carbohydrates / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000208:ethnology / Q000235:genetics*; D016014:Linear Models; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D013030:Spain / Q000453:epidemiology; D044465:White People / Q000235:genetics*
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; C538963:CRY1 protein, human; D056931:Cryptochromes; D004040:Dietary Carbohydrates; D007328:Insulin
keywords: CRY1; Carbohydrate intake; diabetes; genetic epidemiology; gene–diet interaction