Sex modifies the association between the CLOCK variant rs1801260 and BMI in school-age children

Abstract

Disruption of circadian rhythms and variations in the FTO gene may interfere with energy homeostasis and play a role in the development of obesity. The current study assessed the association of common polymorphisms in the CLOCK and FTO genes with standardized body mass index scores (BMI z-scores) and their potential modification of the impact of a culinary nutrition and physical activity intervention in school-age children. Anthropometric measurements were collected in 121 children at the baseline and one-year follow-up of a controlled trial of a school-based culinary nutrition and physical activity intervention. Genotypes of the CLOCK polymorphism (rs1801260) and the FTO polymorphism (rs9939609) were obtained from buccal swabs. Linear mixed-effects regression was applied to evaluate the genetic association and adjust for clusters within families and schools. In our participants, obesity affected 6.6% (8/121) of the children at the baseline and 6.4% (7/109) of the children at the follow-up. The associations between the age-and sex-adjusted BMI z-scores and the two polymorphisms did not reach statistically significance. Yet, sex potentially modified the association between rs1801260 and BMI z-scores. In girls, the G allele carriers had a higher BMI z-scores at the baseline and the follow-up. These polymorphisms did not modify the effect of our culinary nutrition and physical activity intervention on BMI z-scores. Sex is a potential modifier for the association between the CLOCK polymorphism, rs1801260, and BMI z-scores in school-age children. Further investigation is warranted to delineate the sex-dependent role of the CLOCK polymorphisms in the development of childhood obesity.

CLOCK 3111TT Genotype Is Associated with Increased Total Cholesterol and Low-Density Lipoprotein Levels in Menopausal Women with a Body Mass Index of at Least 25 kg/m2

“…It is currently supposed that being overweight may be associated with 3111T/C SNP of the CLOCK gene, but the results of studies on the matter are ambiguous [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ]. Here, we found no differences in the prevalence of genotypes and alleles of 3111T/C SNP of the CLOCK gene in women that had a normal weight or were overweight.…”

“…In a study examining the effect of diet on the lipid profile in overweight and obese patients, including those with metabolic syndrome and coronary heart disease, there were no differences in lipid profile parameters in groups with different 3111T/C SNPs of their CLOCK gene [ 14 , 15 , 16 ]. It should be noted that the researchers did not differentiate their groups by gender, although it has been found that 3111T/C SNP of the CLOCK gene is associated with the risk of overweight/obesity only in women [ 17 , 18 ].…”

“…The results of studies by Galbete C et al (2012) showed that the minor allele SNP 3111T/C of the CLOCK gene could be associated with decreased overweight/obesity risk in elderly women [ 17 ]. A study involving girls showed C -allele and an increased body mass index (BMI) association [ 18 ]. Data on lipid profile parameters depending on the studied polymorphism genotype were not presented in either study.…”

CLOCK Gene Variation Is Associated with the Incidence of Metabolic Syndrome Modulated by Monounsaturated Fatty Acids

“…CLOCK rs1801260 polymorphisms have been suggested to be associated with obesity [ 4 , 15 , 30 , 31 , 32 , 33 ], depression [ 16 ] and Parkinson’s disease [ 34 ]. Among obese patients, individuals with the G minor alleles of rs1801260 (GG + AG) showed higher BMI values compared with those carrying the major allele (AA), and obese patients with the minor allele of rs1801260 were resistant to losing weight compared to those with the major allele [ 31 ].…”

“…This suggests that the CLOCK rs1801260 polymorphism is associated with body weight reduction. In school-age girls with the G allele, carriers of rs1801260 showed increased BMI z-scores at baseline and follow-up [ 30 ]. Elderly subjects with the minor allele (rs1801260 GG type) had lower scores on the depression geriatric scale, predisposing greater risk for depression [ 16 ].…”