Beneficial effect of CLOCK gene polymorphism rs1801260 in combination with low-fat diet on insulin metabolism in the patients with metabolic syndrome.
Study Goal
The researchers aimed to determine whether a low-fat diet modulates associations between CLOCK gene polymorphisms and glucose/lipid metabolism traits in MetS patients compared to a Mediterranean diet.
Results Summary
The study found that a low-fat diet improved insulin sensitivity and reduced insulin resistance in MetS patients homozygous for the major allele (TT) of the CLOCK gene rs1801260 SNP, while no significant effects were observed in the Mediterranean diet group.
Population
475 MetS patients participating in the CORDIOPREV clinical trial.
Effective Dosage
28% fat (12% MUFA) in the low-fat diet group.
Duration
12 months.
Interactions
None mentioned.
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
low-fat diet | decrease | plasma insulin concentrations | MetS subjects homozygous for the major allele (TT) at rs1801260 SNP | - | displayed lower | #1 |
low-fat diet | decrease | insulin resistance (HOMA-IR) | MetS subjects homozygous for the major allele (TT) at rs1801260 SNP | - | displayed lower | #2 |
low-fat diet | increase | insulin sensitivity (QUICKI) | MetS subjects homozygous for the major allele (TT) at rs1801260 SNP | - | displayed higher | #3 |
Mediterranean diet enriched with olive oil | no change | glucose and insulin-related traits | MetS subjects with different CLOCK genotypes (rs1801260 SNP) | - | no significant differences were found | #4 |
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.