|DASHTI, HASSAN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|SMITH, CAREN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|LEE, YU-CHI - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|Lai, Chao Qiang|
|ARNETT, DONNA - University Of Alabama|
|ORDOVAS, JOSE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|GARAULET, MARTA - Universidad De Murcia|
Submitted to: Chronobiology International
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/20/2014
Publication Date: 6/1/2014
Citation: Dashti, H.S., Smith, C.E., Lee, Y., Parnell, L.D., Lai, C., Arnett, D.K., Ordovas, J.M., Garaulet, M. 2014. CRY1 circadian gene variant interacts with carbohydrate intake for insulin resistance in two independent populations: Mediterranean and North American. Chronobiology International. 31(5):660-668. DOI: 10.3109/07420528.2014.886587.
Interpretive Summary: The body’s circadian system governs numerous aspects of human physiology, including the sleep-wake cycle and glucose metabolism. This system has an underlying genetic component and is maintained by a group of genes including CLOCK, BMAL1 and two cryptochromes, CRY1 and CRY2. The cryptochrome genes specifically are also known to influence glucose metabolism, additionally, suggesting that genetic variants disrupting the function of these genes may be associated with increased risk for insulin resistance, insensitive response to insulin increase, and type 2 diabetes in human. Diet is also a regulator of these genes. Therefore we examined how genetic variation in CRY1 could alter the association between carbohydrate intake and insulin resistance in two independent populations: a Mediterranean and a European origin North American population. Our results suggest that consuming a diet high in carbohydrates can increase insulin resistance, only among individuals with a specific CRY1 genetic variant, whereas individuals lacking that genetic variant and consuming a high carbohydrate diet do not have an increased risk of insulin resistance. Therefore, the harmful effects of high carbohydrate diet on insulin resistance are only evident in specific individuals. These results provide further evidence of the link between circadian system and insulin resistance. More importantly, these findings assist in identifying personalized nutrition therapies aimed at lowering the risk of insulin resistance and type 2 diabetes.
Technical 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 a 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. Additionally, 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 < .05). Findings from the meta-analyses of carbohydrate-SNP interactions indicated that an increase in carbohydrate intake (% of energy intake) was associated with a significant increase in HOMA-IR (P = .011), fasting insulin (P = .007) and a decrease in QUICKI (P = .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.