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


CONCLUSIONS
Genetic variation in the NOC gene is associated with BMI in Chinese subjects.
Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Yi-Cheng
YC
Chang
Yen-Feng
YF
Chiu
Pi-Hua
PH
Liu
Siow Wei
SW
Hee
Tien-Jyun
TJ
Chang
Yi-Der
YD
Jiang
Wei-Jei
WJ
Lee
Po-Chu
PC
Lee
Hui-Yi
HY
Kao
Juey-Jen
JJ
Hwang
Lee-Ming
LM
Chuang
D000273:Adipose Tissue / Q000378:metabolism; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000235:genetics; D015992:Body Mass Index; D047390:Casein Kinase II / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D056426:Genetic Loci / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008660:Metabolism / Q000235:genetics; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D009765:Obesity / Q000097:blood / Q000235:genetics / Q000503:physiopathology; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D013624:Taiwan; D014157:Transcription Factors / Q000235:genetics*; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D009687:Nuclear Proteins; D014157:Transcription Factors; D014280:Triglycerides; C102804:nocturnin; D047390:Casein Kinase II