Interaction of Cry1 Gene Polymorphisms and Dominant Food Patterns on Obesity: A Cross‑Sectional Study

Hadith Tangestani, Hadi Emamat, Mir Saeed Yekaninejad, Mohsen Alipour, Seyed Ali Keshavarz, Khadijeh Mirzaei


Background: Evidence suggests that there is some relationship between circadian clock gene variants and obesity. However, there are few examinations supporting this observation in human subjects. This study was aimed to investigate the interaction between Cry1 circadian gene polymorphism and major dietary patterns on obesity measurements.

Methods: Healthy overweight and obese women aged 18–53 years old were recruited from health centers in Tehran, Iran by a multistage cluster random sampling method (n = 377). Major dietary patterns were elicited after assessing the intake of 16 food groups using a valid and reliable 147‑item food frequency questionnaire (FFQ). Anthropometric measurements were performed for each and every participant. Body composition was analyzed using bioelectrical impedance analysis (BIA). Socio‑demographic and physical activity data were also collected by a validated Farsi demographic questionnaire and the international physical activity questionnaire (IPAQ). The Cry1 rs2287161 polymorphism were genotyped using polymerase chain reaction‑restriction fragment length polymorphism (PCR‑RFLP). Generalized linear models were used for interaction analysis.

Results: Two major dietary patterns, including healthy and unhealthy dietary pattern (HDP and UDP, respectively) were determined using factor analysis. Our study showed a significant higher weight (P = 0.003), body mass index (BMI) (P = 0.042), hip circumference (P = 0.052), and body fat mass (P = 0.028) in carriers of C allele compared with G allele. Moreover, a significant gene‑diet interaction was observed between being a carrier of C allele and BMI (P = 0.099 for CC genotype; P = 0.1 for CG genotype) and fat mass (P = 0.1 for CG genotype).

Conclusions: The current study suggests a significant interaction of Cry1 rs2287161 gene polymorphisms in people following a healthy dietary pattern on BMI and fat mass among carriers of C allele compared to carriers of G allele.


Circadian clocks; diet; dietary patterns and Cry1 gene polymorphisms; fat body; geneenvironment interaction; obesity

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Collaboration NRF. Trends in adult body‑mass index in 200

countries from 1975 to 2014: A pooled analysis of 1698

population‑based measurement studies with 19·2 million

participants. Lancet 2016;387:1377‑96.

Nair SC, Sheikh SM, Ibrahim H. Higher physician body mass

index is associated with increased weight bias in an Arab Country

with high prevalence of obesity. Int J Prev Med 2019;10:93.

Finkelstein EA, Khavjou OA, Thompson H, Trogdon JG, Pan L,

Sherry B, et al. Obesity and severe obesity forecasts through

Am J Prev Med 2012;42:563‑70.

Sepúlveda J, Murray C. The state of global health in 2014.

Science 2014;345:1275‑8.

Haidari F, Abiri B, Haghighizadeh M‑H, Kayedani GA,

Birgani NK. Association of hematological parameters with

obesity‑induced inflammation among young females in Ahvaz,

South‑West of Iran. Int J Prev Med 2020;11:55.

Milagro F, Mansego M, De Miguel C, Martinez J. Dietary

factors, epigenetic modifications and obesity outcomes:

Progresses and perspectives. Mol Aspects Med 2013;34:782‑812.

Lavebratt C, Almgren M, Ekström T. Epigenetic regulation in

obesity. Int J Obes 2012;36:757‑65.

Qi L. Gene–diet interaction and weight loss. Curr Opin Lipidol


Ripperger JA, Schibler U. Circadian regulation of gene

expression in animals. Curr Opin Cell Biol 2001;13:357‑62.

Lowrey PL, Takahashi JS. Mammalian circadian biology:

Elucidating genome‑wide levels of temporal organization. Annu

Rev Genomics Hum Genet 2004;5:407‑41.

Moynihan Ramsey K, Marcheva B, Kohsaka A, Bass J. The

clockwork of metabolism. Annu Rev Nutr 2007;27:219‑40.

Zhang EE, Liu Y, Dentin R, Pongsawakul PY, Liu AC,

Hirota T, et al. Cryptochrome mediates circadian regulation

of cAMP signaling and hepatic gluconeogenesis. Nature Med


Ando H, Yanagihara H, Hayashi Y, Obi Y, Tsuruoka S,

Takamura T, et al. Rhythmic messenger ribonucleic acid

expression of clock genes and adipocytokines in mouse visceral

adipose tissue. Endocrinology 2005;146:5631‑6.

Turek FW, Joshu C, Kohsaka A, Lin E, Ivanova G,

McDearmon E, et al. Obesity and metabolic syndrome in

circadian Clock mutant mice. Science 2005;308:1043‑5.

Ye D, Cai S, Jiang X, Ding Y, Chen K, Fan C, et al. Associations

of polymorphisms in circadian genes with abdominal obesity in

Chinese adult population. Obes Res Clin Pract 2016;10:S133‑41.

Reutrakul S, Hood MM, Crowley SJ, Morgan MK, Teodori M,

Knutson KL. The relationship between breakfast skipping,

chronotype, and glycemic control in type 2 diabetes. Chronobiol

Int 2014;31:64‑71.

Kanerva N, Kronholm E, Partonen T, Ovaskainen ML,

Kaartinen NE, Konttinen H, et al. Tendency toward eveningness

is associated with unhealthy dietary habits. Chronobiol Int


Patterson F, Malone SK, Lozano A, Grandner MA, Hanlon AL.

Smoking, screen‑based sedentary behavior, and diet associated

with habitual sleep duration and chronotype: Data from the UK

Biobank. Ann Behav Med 2016;50:715‑26.

Newby P, Tucker KL. Empirically derived eating patterns using

factor or cluster analysis: A review. Nutr Rev 2004;62:177‑203.

Peduzzi P, Concato J, Kemper E, Holford TR, Feinstein AR.

A simulation study of the number of events per variable in

logistic regression analysis. J Clin Epidemiol 1996;49:1373‑9.

Garmaroudi GR, Moradi A. Socio‑economic status in Iran:

A study of measurement index. Payesh (Health Monitor)


Asghari G, Rezazadeh A, Hosseini‑Esfahani F, Mehrabi Y,

Mirmiran P, Azizi F. Reliability, comparative validity and

stability of dietary patterns derived from an FFQ in the Tehran

Lipid and Glucose Study. Br J Nutr 2012;108:1109‑17.

Lee PH, Macfarlane DJ, Lam TH, Stewart SM. Validity

of the international physical activity questionnaire short

form (IPAQ‑SF): A systematic review. Int J Behav Nutr Phys Act


Moghaddam MB, Aghdam FB, Jafarabadi MA,

Allahverdipour H, Nikookheslat SD, Safarpour S. The Iranian

Version of International Physical Activity Questionnaire (IPAQ)

in Iran: Content and construct validity, factor structure, internal

consistency and stability. World Appl Sci J 2012;18:1073‑80.

Committee IR. Guidelines for data processing and analysis of the

International Physical Activity Questionnaire (IPAQ)‑short and

long forms. Available from: http://www ipaq ki se/scoring.pdf.

[Last accessed on 2022 Aug 03].

Garaulet M, Lee Y‑C, Shen J, Parnell LD, Arnett DK, Tsai MY,

et al. CLOCK genetic variation and metabolic syndrome risk:

Modulation by monounsaturated fatty acids. Am J Clin Nutr


Sánchez‑Muniz F, Simón Martín C. Clock genes,

chronodisruption, nutrition and obesity. Curr Res Diabetes Obes

J 2 017;3:1-6

Wang T, Heianza Y, Sun D, Huang T, Ma W, Rimm EB, et al.

Improving adherence to healthy dietary patterns, genetic risk,

and long term weight gain: Gene‑diet interaction analysis in

two prospective cohort studies. BMJ 2018;360. doi: 10.1136/


Xiang L, Wu H, Pan A, Patel B, Xiang G, Qi L, et al. FTO

genotype and weight loss in diet and lifestyle interventions:

A systematic review and meta‑analysis. Am J Clin Nutr


Lopez‑Minguez J, Gómez‑Abellán P, Garaulet M. Circadian

rhythms, food timing and obesity. Proc Nutr Soc 2016;75:501‑11.

Garaulet M, Tardido AE, Lee Y, Smith C, Parnell L, Ordovas J.

SIRT1 and CLOCK 3111T>C combined genotype is associated

with evening preference and weight loss resistance in a behavioral

therapy treatment for obesity. Int J Obes 2012;36:1436‑41.

Sherman H, Genzer Y, Cohen R, Chapnik N, Madar Z, Froy O.

Timed high‑fat diet resets circadian metabolism and prevents

obesity. FASEB J 2012;26:3493‑502.

Duez H, Staels B. Rev‑erbα gives a time cue to metabolism.

FEBS Lett 2008;582:19‑25.

Yin L, Wu N, Curtin JC, Qatanani M, Szwergold NR, Reid RA,

et al. Rev‑erbα, a heme sensor that coordinates metabolic and

circadian pathways. Science 2007;318:1786‑9.

Yanagihara H, Ando H, Hayashi Y, Obi Y, Fujimura A. High‐fat

feeding exerts minimal effects on rhythmic mRNA expression

of clock genes in mouse peripheral tissues. Chronobiol Int


Cano P, Jiménez‑Ortega V, Larrad A, Toso CFR, Cardinali DP,

Esquifino AI. Effect of a high‑fat diet on 24‑h pattern of

circulating levels of prolactin, luteinizing hormone, testosterone,

corticosterone, thyroid‑stimulating hormone and glucose, and

pineal melatonin content, in rats. Endocrine 2008;33:118‑25.

Garaulet M, Corbalán‑Tutau MD, Madrid JA, Baraza JC,

Parnell LD, Lee Y‑C, et al. PERIOD2 variants are associated with

abdominal obesity, psycho‑behavioral factors, and attrition in the

dietary treatment of obesity. J Am Diet Assoc 2010;110:917‑21.

Soria V, Martínez‑Amorós È, Escaramís G, Valero J,

Pérez‑Egea R, García C, et al. Differential association of

circadian genes with mood disorders: CRY1 and NPAS2

are associated with unipolar major depression and CLOCK

and VIP with bipolar disorder. Neuropsychopharmacology


McElroy SL, Kotwal R, Malhotra S, Nelson EB, Keck PE Jr,

Nemeroff CB. Are mood disorders and obesity related? A

review for the mental health professional. J Clin Psychiatry


Mansur RB, Brietzke E, McIntyre RS. Is there a “metabolic‑mood

syndrome”? A review of the relationship between obesity and

mood disorders. Neurosci Biobehav Rev 2015;52:89‑104.

Oishi K, Ohkura N, Wakabayashi M, Shirai H, Sato K,

Matsuda J, et al. CLOCK is involved in obesity‐induced

disordered fibrinolysis in ob/ob mice by regulating PAI‐1 gene

expression. J Thromb Haemost 2006;4:1774‑80.

Rudic RD, McNamara P, Curtis A‑M, Boston RC, Panda S,

Hogenesch JB, et al. BMAL1 and CLOCK, two essential

components of the circadian clock, are involved in glucose

homeostasis. PLoS Biol 2004;2:e377.

Naska A, Lagiou A, Lagiou P. Dietary assessment methods in

epidemiological research: Current state of the art and future

prospects. F1000Research 2017;6:926.