CLOCK 3111T/C Genetic Variant Influences the Daily Rhythm of Autonomic Nervous Function: Relevance to Body Weight Control

Overview

Journal Int J Obes (Lond)

Specialty Endocrinology

Date 2017 Jul 25

PMID 28736443

Citations 5

Authors

M-T Lo

C Bandin

H-W Yang

F A J L Scheer

K Hu

M Garaulet

Affiliations

Soon will be listed here.

Abstract

Background/objectives: Humans carrying the genetic risk variant C at the circadian CLOCK (Circadian Locomotor Output Cycles Kaput) 3111T/C have been shown to have more difficulties to achieve desired weight loss than TT carriers. We tested the hypothesis that the daily rhythm of autonomic nervous function differs in CLOCK 3111C carriers, leading to reduced effectiveness in weight control.

Subjects/methods: We recruited 40 overweight/obese Caucasian women (body mass index>25), 20 carrying CLOCK 3111C (CC and TC) and 20 non-carriers with matched age and body mass index who participated in a dietary obesity treatment program of up to 30 weeks. Following the treatment, ambulatory electrocardiography was continuously monitored for up to 3.5 days when subjects underwent their normal daily activities. To assess autonomic function, heart rate variability analysis (HRV) was performed hourly to obtain mean inter-beat interval between two consecutive R waves (mean RR) and s.d. of normal-to-normal heartbeat intervals (SDNN), and two parasympathetic measures, namely, proportion of differences between adjacent NN intervals that are >50 ms (pNN50), and high-frequency (HF: 0.15-0.4 Hz) power.

Results: In the TT carriers, all tested HRV indices showed significant daily rhythms (all P-values <0.0001) with lower mean RR, SDNN, pNN50, and HF during the daytime as compared with the nighttime. The amplitudes of these rhythms except for SDNN were reduced significantly in the C carriers (mean RR: ~19.7%, P=0.001; pNN50: 58.1%, P=0.001; and HF: 41.1%, P=0.001). In addition, subjects with less weight loss during the treatment program had smaller amplitudes in the rhythms of mean RR (P<0.0001), pNN50 (P=0.007) and HF (P=0.003). Furthermore, the rhythmicity-weight loss associations were much stronger in the C carriers as compared to the TT carriers (mean RR: P=0.028, pNN50: P=0.0002; HF: P=0.015).

Conclusions: The daily rhythm of parasympathetic modulation may play a role in the influence of the CLOCK variation on body weight control.

Citing Articles

Independent effects of the human circadian system and sleep/eating cycles on caloric intake in adolescents vary by weight status.

Barker D, Carskadon M, Gredvig-Ardito C, Hart C, Raynor H, Scheer F Proc Natl Acad Sci U S A. 2025; 122(8):e2407907122.

PMID: 39964717 PMC: 11874483. DOI: 10.1073/pnas.2407907122.

Effects of Dietary Fat to Carbohydrate Ratio on Obesity Risk Depending on Genotypes of Circadian Genes.

Shon J, Han Y, Park Y Nutrients. 2022; 14(3).

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Aggregating heart rate variability indices across sleep stage epochs ignores significant variance through the night.

Eddie D, Bentley K, Bernard R, Mischoulon D, Winkelman J Sleep Med. 2022; 90:262-266.

PMID: 35228137 PMC: 8923916. DOI: 10.1016/j.sleep.2021.11.020.

Daily Rhythm of Fractal Cardiac Dynamics Links to Weight Loss Resistance: Interaction with 3111T/C Genetic Variant.

Yang H, Garaulet M, Li P, Bandin C, Lin C, Lo M Nutrients. 2021; 13(7).

PMID: 34371977 PMC: 8308644. DOI: 10.3390/nu13072463.

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

Meng Y, Lohse B, Cunningham-Sabo L PLoS One. 2020; 15(8):e0236991.

PMID: 32785234 PMC: 7423126. DOI: 10.1371/journal.pone.0236991.

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