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CLOCK gene variation is associated with incidence of type-2 diabetes and cardiovascular diseases in type-2 diabetic subjects: dietary modulation in the PREDIMED randomized trial.

BACKGROUNDCircadian rhythms regulate key biological processes influencing metabolic pathways. Disregulation is associated with type 2 diabetes (T2D) and cardiovascular diseases (CVD). Circadian rhythms are generated by a transcriptional autoregulatory feedback loop involving core clock genes. CLOCK... Full description

Journal Title: Cardiovascular diabetology January 7, 2016, Vol.15, p.4
Main Author: Corella, Dolores
Other Authors: Asensio, Eva M , Coltell, Oscar , Sorlí, José V , Estruch, Ramón , Martínez-González, Miguel Ángel , Salas-Salvadó, Jordi , Castañer, Olga , Arós, Fernando , Lapetra, José , Serra-Majem, Lluís , Gómez-Gracia, Enrique , Ortega-Azorín, Carolina , Fiol, Miquel , Espino, Javier Díez , Díaz-López, Andrés , Fitó, Montserrat , Ros, Emilio , Ordovás, José M
Format: Electronic Article Electronic Article
Language: English
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ID: E-ISSN: 1475-2840 ; DOI: 1475-2840 ; DOI: 10.1186/s12933-015-0327-8
Link: http://search.proquest.com/docview/1760867974/?pq-origsite=primo
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title: CLOCK gene variation is associated with incidence of type-2 diabetes and cardiovascular diseases in type-2 diabetic subjects: dietary modulation in the PREDIMED randomized trial.
format: Article
creator:
  • Corella, Dolores
  • Asensio, Eva M
  • Coltell, Oscar
  • Sorlí, José V
  • Estruch, Ramón
  • Martínez-González, Miguel Ángel
  • Salas-Salvadó, Jordi
  • Castañer, Olga
  • Arós, Fernando
  • Lapetra, José
  • Serra-Majem, Lluís
  • Gómez-Gracia, Enrique
  • Ortega-Azorín, Carolina
  • Fiol, Miquel
  • Espino, Javier Díez
  • Díaz-López, Andrés
  • Fitó, Montserrat
  • Ros, Emilio
  • Ordovás, José M
subjects:
  • Aged–Genetics
  • Aged, 80 and Over–Diagnosis
  • Clock Proteins–Epidemiology
  • Cardiovascular Diseases–Genetics
  • Chi-Square Distribution–Physiopathology
  • Circadian Rhythm–Prevention & Control
  • Diabetes Mellitus, Type 2–Genetics
  • Diet, Mediterranean–Diagnosis
  • Gene Frequency–Epidemiology
  • Gene-Environment Interaction–Genetics
  • Genetic Predisposition to Disease–Physiopathology
  • Heterozygote–Prevention & Control
  • Homozygote–Epidemiology
  • Humans–Epidemiology
  • Incidence–Epidemiology
  • Kaplan-Meier Estimate–Epidemiology
  • Longitudinal Studies–Epidemiology
  • Male–Epidemiology
  • Middle Aged–Epidemiology
  • Multivariate Analysis–Epidemiology
  • Phenotype–Epidemiology
  • Polymorphism, Single Nucleotide–Epidemiology
  • Proportional Hazards Models–Epidemiology
  • Protective Factors–Epidemiology
  • Risk Assessment–Epidemiology
  • Risk Factors–Epidemiology
  • Spain–Epidemiology
  • Time Factors–Epidemiology
  • Treatment Outcome–Epidemiology
  • Clock Proteins
  • Clock Protein, Human
ispartof: Cardiovascular diabetology, January 7, 2016, Vol.15, p.4
description: BACKGROUNDCircadian rhythms regulate key biological processes influencing metabolic pathways. Disregulation is associated with type 2 diabetes (T2D) and cardiovascular diseases (CVD). Circadian rhythms are generated by a transcriptional autoregulatory feedback loop involving core clock genes. CLOCK (circadian locomotor output cycles protein kaput), one of those core genes, is known to regulate glucose metabolism in rodent models. Cross-sectional studies in humans have reported associations between this locus and obesity, plasma glucose, hypertension and T2D prevalence, supporting its role in cardiovascular risk. However, no longitudinal study has investigated the association between CLOCK gene variation and T2D or CVD incidence. Moreover, although in a previous work we detected a gene-diet interaction between the CLOCK-rs4580704 (C > G) single nucleotide polymorphism (SNP) and monounsaturated (MUFA) intake on insulin resistance, no interventional study has analyzed gene-diet interactions on T2D or CVD outcomes. METHODSWe analyzed the association between the CLOCK-rs4580704 SNP and incidence of T2D and CVD longitudinally in 7098 PREDIMED trial (ISRCTN35739639) participants after a median 4.8-year follow-up. We also examined modulation by Mediterranean diet (MedDiet) intervention (high in MUFA) on these associations. RESULTSWe observed a significant association between the CLOCK-rs4580704 SNP and T2D incidence in n = 3671 non-T2D PREDIMED participants, with variant allele (G) carriers showing decreased incidence (dominant model) compared with CC homozygotes (HR: 0.69; 95 % CI 0.54-0.87; P = 0.002). This protection was more significant in the MedDiet intervention group (HR: 0.58; 95 % CI 0.43-0.78; P < 0.001) than in the control group (HR: 0.95; 95 % CI 0.63-1.44; P = 0.818). Moreover, we detected a statistically significant interaction (P = 0.018) between CLOCK-rs4580704 SNP and T2D status on stroke. Thus, only in T2D subjects was CLOCK-rs4580704 SNP associated with stroke risk, G-carriers having decreased risk (HR: 0.61; 95 % CI 0.40-0.94; P = 0.024 versus CC) in the multivariable-adjusted model. CONCLUSIONSIn agreement with our previous results showing a protective effect of the G-allele against hyperglycemia, we extended our findings by reporting a novel association with lower T2D incidence and also suggesting a dietary modulation. Moreover, we report for the first time an association between a CLOCK polymorphism and stroke in T2D subjects, suggesting tha
language: eng
source:
identifier: E-ISSN: 1475-2840 ; DOI: 1475-2840 ; DOI: 10.1186/s12933-015-0327-8
fulltext: fulltext
issn:
  • 14752840
  • 1475-2840
url: Link


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titleCLOCK gene variation is associated with incidence of type-2 diabetes and cardiovascular diseases in type-2 diabetic subjects: dietary modulation in the PREDIMED randomized trial.
creatorCorella, Dolores ; Asensio, Eva M ; Coltell, Oscar ; Sorlí, José V ; Estruch, Ramón ; Martínez-González, Miguel Ángel ; Salas-Salvadó, Jordi ; Castañer, Olga ; Arós, Fernando ; Lapetra, José ; Serra-Majem, Lluís ; Gómez-Gracia, Enrique ; Ortega-Azorín, Carolina ; Fiol, Miquel ; Espino, Javier Díez ; Díaz-López, Andrés ; Fitó, Montserrat ; Ros, Emilio ; Ordovás, José M
contributorCorella, Dolores (correspondence author) ; Corella, Dolores (record owner)
ispartofCardiovascular diabetology, January 7, 2016, Vol.15, p.4
identifier
subjectAged–Genetics ; Aged, 80 and Over–Diagnosis ; Clock Proteins–Epidemiology ; Cardiovascular Diseases–Genetics ; Chi-Square Distribution–Physiopathology ; Circadian Rhythm–Prevention & Control ; Diabetes Mellitus, Type 2–Genetics ; Diet, Mediterranean–Diagnosis ; Gene Frequency–Epidemiology ; Gene-Environment Interaction–Genetics ; Genetic Predisposition to Disease–Physiopathology ; Heterozygote–Prevention & Control ; Homozygote–Epidemiology ; Humans–Epidemiology ; Incidence–Epidemiology ; Kaplan-Meier Estimate–Epidemiology ; Longitudinal Studies–Epidemiology ; Male–Epidemiology ; Middle Aged–Epidemiology ; Multivariate Analysis–Epidemiology ; Phenotype–Epidemiology ; Polymorphism, Single Nucleotide–Epidemiology ; Proportional Hazards Models–Epidemiology ; Protective Factors–Epidemiology ; Risk Assessment–Epidemiology ; Risk Factors–Epidemiology ; Spain–Epidemiology ; Time Factors–Epidemiology ; Treatment Outcome–Epidemiology ; Clock Proteins ; Clock Protein, Human
descriptionBACKGROUNDCircadian rhythms regulate key biological processes influencing metabolic pathways. Disregulation is associated with type 2 diabetes (T2D) and cardiovascular diseases (CVD). Circadian rhythms are generated by a transcriptional autoregulatory feedback loop involving core clock genes. CLOCK (circadian locomotor output cycles protein kaput), one of those core genes, is known to regulate glucose metabolism in rodent models. Cross-sectional studies in humans have reported associations between this locus and obesity, plasma glucose, hypertension and T2D prevalence, supporting its role in cardiovascular risk. However, no longitudinal study has investigated the association between CLOCK gene variation and T2D or CVD incidence. Moreover, although in a previous work we detected a gene-diet interaction between the CLOCK-rs4580704 (C > G) single nucleotide polymorphism (SNP) and monounsaturated (MUFA) intake on insulin resistance, no interventional study has analyzed gene-diet interactions on T2D or CVD outcomes. METHODSWe analyzed the association between the CLOCK-rs4580704 SNP and incidence of T2D and CVD longitudinally in 7098 PREDIMED trial (ISRCTN35739639) participants after a median 4.8-year follow-up. We also examined modulation by Mediterranean diet (MedDiet) intervention (high in MUFA) on these associations. RESULTSWe observed a significant association between the CLOCK-rs4580704 SNP and T2D incidence in n = 3671 non-T2D PREDIMED participants, with variant allele (G) carriers showing decreased incidence (dominant model) compared with CC homozygotes (HR: 0.69; 95 % CI 0.54-0.87; P = 0.002). This protection was more significant in the MedDiet intervention group (HR: 0.58; 95 % CI 0.43-0.78; P < 0.001) than in the control group (HR: 0.95; 95 % CI 0.63-1.44; P = 0.818). Moreover, we detected a statistically significant interaction (P = 0.018) between CLOCK-rs4580704 SNP and T2D status on stroke. Thus, only in T2D subjects was CLOCK-rs4580704 SNP associated with stroke risk, G-carriers having decreased risk (HR: 0.61; 95 % CI 0.40-0.94; P = 0.024 versus CC) in the multivariable-adjusted model. CONCLUSIONSIn agreement with our previous results showing a protective effect of the G-allele against hyperglycemia, we extended our findings by reporting a novel association with lower T2D incidence and also suggesting a dietary modulation. Moreover, we report for the first time an association between a CLOCK polymorphism and stroke in T2D subjects, suggesting that core clock genes may significantly contribute to increased CVD risk in T2D.
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2Coltell, Oscar
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6Salas-Salvadó, Jordi
7Castañer, Olga
8Arós, Fernando
9Lapetra, José
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11Gómez-Gracia, Enrique
12Ortega-Azorín, Carolina
13Fiol, Miquel
14Espino, Javier Díez
15Díaz-López, Andrés
16Fitó, Montserrat
17Ros, Emilio
18Ordovás, José M
titleCLOCK gene variation is associated with incidence of type-2 diabetes and cardiovascular diseases in type-2 diabetic subjects: dietary modulation in the PREDIMED randomized trial.
descriptionBACKGROUNDCircadian rhythms regulate key biological processes influencing metabolic pathways. Disregulation is associated with type 2 diabetes (T2D) and cardiovascular diseases (CVD). Circadian rhythms are generated by a transcriptional autoregulatory feedback loop involving core clock genes. CLOCK (circadian locomotor output cycles protein kaput), one of those core genes, is known to regulate glucose metabolism in rodent models. Cross-sectional studies in humans have reported associations between this locus and obesity, plasma glucose, hypertension and T2D prevalence, supporting its role in cardiovascular risk. However, no longitudinal study has investigated the association between CLOCK gene variation and T2D or CVD incidence. Moreover, although in a previous work we detected a gene-diet interaction between the CLOCK-rs4580704 (C > G) single nucleotide polymorphism (SNP) and monounsaturated (MUFA) intake on insulin resistance, no interventional study has analyzed gene-diet interactions on T2D or CVD outcomes. METHODSWe analyzed the association between the CLOCK-rs4580704 SNP and incidence of T2D and CVD longitudinally in 7098 PREDIMED trial (ISRCTN35739639) participants after a median 4.8-year follow-up. We also examined modulation by Mediterranean diet (MedDiet) intervention (high in MUFA) on these associations. RESULTSWe observed a significant association between the CLOCK-rs4580704 SNP and T2D incidence in n = 3671 non-T2D PREDIMED participants, with variant allele (G) carriers showing decreased incidence (dominant model) compared with CC homozygotes (HR: 0.69; 95 % CI 0.54-0.87; P = 0.002). This protection was more significant in the MedDiet intervention group (HR: 0.58; 95 % CI 0.43-0.78; P < 0.001) than in the control group (HR: 0.95; 95 % CI 0.63-1.44; P = 0.818). Moreover, we detected a statistically significant interaction (P = 0.018) between CLOCK-rs4580704 SNP and T2D status on stroke. Thus, only in T2D subjects was CLOCK-rs4580704 SNP associated with stroke risk, G-carriers having decreased risk (HR: 0.61; 95 % CI 0.40-0.94; P = 0.024 versus CC) in the multivariable-adjusted model. CONCLUSIONSIn agreement with our previous results showing a protective effect of the G-allele against hyperglycemia, we extended our findings by reporting a novel association with lower T2D incidence and also suggesting a dietary modulation. Moreover, we report for the first time an association between a CLOCK polymorphism and stroke in T2D subjects, suggesting that core clock genes may significantly contribute to increased CVD risk in T2D.
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0Aged–Genetics
1Aged, 80 and Over–Diagnosis
2Clock Proteins–Epidemiology
3Cardiovascular Diseases–Genetics
4Chi-Square Distribution–Physiopathology
5Circadian Rhythm–Prevention & Control
6Diabetes Mellitus, Type 2–Genetics
7Diet, Mediterranean–Diagnosis
8Gene Frequency–Epidemiology
9Gene-Environment Interaction–Genetics
10Genetic Predisposition to Disease–Physiopathology
11Heterozygote–Prevention & Control
12Homozygote–Epidemiology
13Humans–Epidemiology
14Incidence–Epidemiology
15Kaplan-Meier Estimate–Epidemiology
16Longitudinal Studies–Epidemiology
17Male–Epidemiology
18Middle Aged–Epidemiology
19Multivariate Analysis–Epidemiology
20Phenotype–Epidemiology
21Polymorphism, Single Nucleotide–Epidemiology
22Proportional Hazards Models–Epidemiology
23Protective Factors–Epidemiology
24Risk Assessment–Epidemiology
25Risk Factors–Epidemiology
26Spain–Epidemiology
27Time Factors–Epidemiology
28Treatment Outcome–Epidemiology
29Clock Proteins
30Clock Protein, Human
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titleCLOCK gene variation is associated with incidence of type-2 diabetes and cardiovascular diseases in type-2 diabetic subjects: dietary modulation in the PREDIMED randomized trial.
authorCorella, Dolores ; Asensio, Eva M ; Coltell, Oscar ; Sorlí, José V ; Estruch, Ramón ; Martínez-González, Miguel Ángel ; Salas-Salvadó, Jordi ; Castañer, Olga ; Arós, Fernando ; Lapetra, José ; Serra-Majem, Lluís ; Gómez-Gracia, Enrique ; Ortega-Azorín, Carolina ; Fiol, Miquel ; Espino, Javier Díez ; Díaz-López, Andrés ; Fitó, Montserrat ; Ros, Emilio ; Ordovás, José M
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1Aged, 80 and Over–Diagnosis
2Clock Proteins–Epidemiology
3Cardiovascular Diseases–Genetics
4Chi-Square Distribution–Physiopathology
5Circadian Rhythm–Prevention & Control
6Diabetes Mellitus, Type 2–Genetics
7Diet, Mediterranean–Diagnosis
8Gene Frequency–Epidemiology
9Gene-Environment Interaction–Genetics
10Genetic Predisposition to Disease–Physiopathology
11Heterozygote–Prevention & Control
12Homozygote–Epidemiology
13Humans–Epidemiology
14Incidence–Epidemiology
15Kaplan-Meier Estimate–Epidemiology
16Longitudinal Studies–Epidemiology
17Male–Epidemiology
18Middle Aged–Epidemiology
19Multivariate Analysis–Epidemiology
20Phenotype–Epidemiology
21Polymorphism, Single Nucleotide–Epidemiology
22Proportional Hazards Models–Epidemiology
23Protective Factors–Epidemiology
24Risk Assessment–Epidemiology
25Risk Factors–Epidemiology
26Spain–Epidemiology
27Time Factors–Epidemiology
28Treatment Outcome–Epidemiology
29Clock Proteins
30Clock Protein, Human
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7Castañer, Olga
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9Lapetra, José
10Serra-Majem, Lluís
11Gómez-Gracia, Enrique
12Ortega-Azorín, Carolina
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addauCorella, Dolores
atitleCLOCK gene variation is associated with incidence of type-2 diabetes and cardiovascular diseases in type-2 diabetic subjects: dietary modulation in the PREDIMED randomized trial.
jtitleCardiovascular diabetology
risdate20160107
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abstractBACKGROUNDCircadian rhythms regulate key biological processes influencing metabolic pathways. Disregulation is associated with type 2 diabetes (T2D) and cardiovascular diseases (CVD). Circadian rhythms are generated by a transcriptional autoregulatory feedback loop involving core clock genes. CLOCK (circadian locomotor output cycles protein kaput), one of those core genes, is known to regulate glucose metabolism in rodent models. Cross-sectional studies in humans have reported associations between this locus and obesity, plasma glucose, hypertension and T2D prevalence, supporting its role in cardiovascular risk. However, no longitudinal study has investigated the association between CLOCK gene variation and T2D or CVD incidence. Moreover, although in a previous work we detected a gene-diet interaction between the CLOCK-rs4580704 (C > G) single nucleotide polymorphism (SNP) and monounsaturated (MUFA) intake on insulin resistance, no interventional study has analyzed gene-diet interactions on T2D or CVD outcomes. METHODSWe analyzed the association between the CLOCK-rs4580704 SNP and incidence of T2D and CVD longitudinally in 7098 PREDIMED trial (ISRCTN35739639) participants after a median 4.8-year follow-up. We also examined modulation by Mediterranean diet (MedDiet) intervention (high in MUFA) on these associations. RESULTSWe observed a significant association between the CLOCK-rs4580704 SNP and T2D incidence in n = 3671 non-T2D PREDIMED participants, with variant allele (G) carriers showing decreased incidence (dominant model) compared with CC homozygotes (HR: 0.69; 95 % CI 0.54-0.87; P = 0.002). This protection was more significant in the MedDiet intervention group (HR: 0.58; 95 % CI 0.43-0.78; P < 0.001) than in the control group (HR: 0.95; 95 % CI 0.63-1.44; P = 0.818). Moreover, we detected a statistically significant interaction (P = 0.018) between CLOCK-rs4580704 SNP and T2D status on stroke. Thus, only in T2D subjects was CLOCK-rs4580704 SNP associated with stroke risk, G-carriers having decreased risk (HR: 0.61; 95 % CI 0.40-0.94; P = 0.024 versus CC) in the multivariable-adjusted model. CONCLUSIONSIn agreement with our previous results showing a protective effect of the G-allele against hyperglycemia, we extended our findings by reporting a novel association with lower T2D incidence and also suggesting a dietary modulation. Moreover, we report for the first time an association between a CLOCK polymorphism and stroke in T2D subjects, suggesting that core clock genes may significantly contribute to increased CVD risk in T2D.
doi10.1186/s12933-015-0327-8
urlhttp://search.proquest.com/docview/1760867974/
issue3
date2016-01-07