Genetic variation in the NOC gene is associated with body mass index in Chinese subjects

PLoS One. 2013 Jul 26;8(7):e69622. doi: 10.1371/journal.pone.0069622. Print 2013.

Abstract

Circadian clock genes are critical regulators of energy homeostasis and metabolism. However, whether variation in the circadian genes is associated with metabolic phenotypes in humans remains to be explored. In this study, we systemically genotyped 20 tag single nucleotide polymorphisms (SNPs) in 8 candidate genes involved in circadian clock, including CLOCK, BMAL1(ARNTL), PER1, PER2, CRY1, CRY2, CSNK1E,, and NOC(CCRN4L) in 1,510 non-diabetic Chinese subjects in Taipei and Yunlin populations in Taiwan. Their associations with metabolic phenotypes were analyzed. We found that genetic variation in the NOC gene, rs9684900 was associated with body mass index (BMI) (P = 0.0016, Bonferroni corrected P = 0.032). Another variant, rs135764 in the CSNK1E gene was associated with fasting glucose (P = 0.0023, Bonferroni corrected P = 0.046). These associations were consistent in both Taipei and Yunlin populations. Significant epistatic and joint effects between SNPs on BMI and related phenotypes were observed. Furthermore, NOC mRNA levels in human abdominal adipose tissue were significantly increased in obese subjects compared to non-obese controls.

Conclusion: Genetic variation in the NOC gene is associated with BMI in Chinese subjects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / metabolism
  • Alleles
  • Asian People / genetics*
  • Blood Glucose / metabolism
  • Blood Pressure / genetics
  • Body Mass Index*
  • Casein Kinase II / genetics
  • Female
  • Genetic Association Studies*
  • Genetic Loci / genetics
  • Humans
  • Linkage Disequilibrium / genetics
  • Male
  • Metabolism / genetics
  • Middle Aged
  • Nuclear Proteins / genetics*
  • Obesity / blood
  • Obesity / genetics
  • Obesity / physiopathology
  • Phenotype
  • Polymorphism, Single Nucleotide / genetics*
  • Risk Factors
  • Taiwan
  • Transcription Factors / genetics*
  • Triglycerides / blood

Substances

  • Blood Glucose
  • Nuclear Proteins
  • Transcription Factors
  • Triglycerides
  • nocturnin
  • Casein Kinase II

Grants and funding

This work was supported in part by a grant (NSC 97–2314-B-002-047-MY3) from the National Science Council of Taiwan and a grant (99C101–601) from the National Taiwan University College of Medicine, Taipei, Taiwan. This study is also partially supported by the grant PH-102-PP-04 from the National Health Research Institutes in Taiwan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.