Garcia-Rios Antonio, Gomez-Delgado Francisco Jesus, Garaulet Marta, Alcala-Diaz Juan Francisco, Delgado-Lista Francisco Javier, Marin Carmen, Rangel-Zuñiga Oriol Alberto, Rodriguez-Cantalejo Fernando, Gomez-Luna Purificacion, Ordovas Jose Maria, Perez-Jimenez Francisco, Lopez-Miranda Jose, Perez-Martinez Pablo
Lipids and Atherosclerosis Unit, IMIBIC/Hospital Universitario Reina Sofía/Universidad de Córdoba , Cordoba , Spain .
Chronobiol Int. 2014 Apr;31(3):401-8. doi: 10.3109/07420528.2013.864300. Epub 2013 Dec 11.
Genetic variation at the Circadian Locomotor Output Cycles Kaput (CLOCK) locus has been associated with lifestyle-related conditions such as obesity, metabolic syndrome (MetS) and cardiovascular diseases. In fact, it has been suggested that the disruption of the circadian system may play a causal role in manifestations of MetS. The aim of this research was to find out whether habitual consumption of a low-fat diet, compared with a Mediterranean diet enriched with olive oil, modulates the associations between common CLOCK single nucleotide polymorphisms (SNPs) (rs1801260, rs3749474 and rs4580704) and lipid and glucose-related traits among MetS patients. Plasma lipid and insulin concentrations, indexes related with insulin resistance (homeostasis model assessment of insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI)) and CLOCK SNPs were determined in 475 MetS subjects participating in the CORDIOPREV clinical trial (NCT00924937). Gene-diet interactions were analyzed after a year of dietary intervention (Mediterranean diet (35% fat, 22% monounsaturated fatty acids (MUFA)) versus low-fat diet (28% fat, 12% MUFA)). We found significant gene-diet interactions between rs1801260 SNP and the dietary pattern for insulin concentrations (p = 0.009), HOMA-IR (p = 0.014) and QUICKI (p = 0.028). Specifically, after 12 months of low-fat intervention, subjects who were homozygous for the major allele (TT) displayed lower plasma insulin concentrations (p = 0.032), lower insulin resistance (HOMA-IR; p = 0.027) and higher insulin sensitivity (QUICKI; p = 0.024) compared with carriers of the minor allele C (TC + CC). In contrast, in the Mediterranean intervention group a different trend was observed although no significant differences were found between CLOCK genotypes after 12 months of treatment. Our data support the notion that a chronic consumption of a healthy diet may play a contributing role in triggering glucose metabolism by interacting with the rs1801260 SNP at CLOCK gene locus in MetS patients. Due to the complex nature of gene-environment interactions, dietary adjustment in subjects with the MetS may require a personalized approach.
昼夜运动输出周期蛋白（CLOCK）基因座的遗传变异与肥胖、代谢综合征（MetS）和心血管疾病等与生活方式相关的疾病有关。事实上，有人提出昼夜节律系统的紊乱可能在MetS的表现中起因果作用。本研究的目的是探究与富含橄榄油的地中海饮食相比，习惯性食用低脂饮食是否会调节常见CLOCK单核苷酸多态性（SNP）（rs1801260、rs3749474和rs4580704）与MetS患者脂质和血糖相关性状之间的关联。在参与CORDIOPREV临床试验（NCT00924937）的475名MetS受试者中测定了血浆脂质和胰岛素浓度、与胰岛素抵抗相关的指标（胰岛素抵抗稳态模型评估（HOMA-IR）和定量胰岛素敏感性检查指数（QUICKI））以及CLOCK SNP。在进行一年的饮食干预后（地中海饮食（35%脂肪，22%单不饱和脂肪酸（MUFA））与低脂饮食（28%脂肪，12% MUFA））分析基因-饮食相互作用。我们发现rs1801260 SNP与饮食模式在胰岛素浓度（p = 0.009）、HOMA-IR（p = 0.014）和QUICKI（p = 0.028）方面存在显著的基因-饮食相互作用。具体而言，在进行12个月的低脂干预后，与次要等位基因C（TC + CC）携带者相比，主要等位基因（TT）纯合子受试者的血浆胰岛素浓度较低（p = 0.032）、胰岛素抵抗较低（HOMA-IR；p = 0.027）且胰岛素敏感性较高（QUICKI；p = 0.024）。相比之下，在地中海干预组中观察到了不同的趋势，尽管在治疗12个月后CLOCK基因型之间未发现显著差异。我们的数据支持这样一种观点，即长期食用健康饮食可能通过与MetS患者CLOCK基因座的rs1801260 SNP相互作用，在触发葡萄糖代谢中发挥作用。由于基因-环境相互作用的复杂性，MetS患者的饮食调整可能需要个性化方法。
