中国人群中 NOC 基因的遗传变异与体重指数相关。
Genetic variation in the NOC gene is associated with body mass index in Chinese subjects.
机构信息
Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
出版信息
PLoS One. 2013 Jul 26;8(7):e69622. doi: 10.1371/journal.pone.0069622. Print 2013.
UNLABELLED
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.
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生物钟基因是能量平衡和代谢的关键调节因子。然而，生物钟基因的变异是否与人类的代谢表型有关仍有待探索。在这项研究中，我们在台北和云林的 1510 名非糖尿病中国受试者中系统地对 8 个生物钟相关候选基因中的 20 个标签单核苷酸多态性（SNP）进行了基因分型，包括 CLOCK、BMAL1(ARNTL)、PER1、PER2、CRY1、CRY2、CSNK1E 和 NOC(CCRN4L)。分析了它们与代谢表型的关联。我们发现，NOC 基因中的遗传变异 rs9684900 与体重指数（BMI）相关（P = 0.0016，Bonferroni 校正后 P = 0.032）。CSNK1E 基因中的另一个变体 rs135764 与空腹血糖相关（P = 0.0023，Bonferroni 校正后 P = 0.046）。这些关联在台北和云林人群中都是一致的。在 BMI 和相关表型上观察到 SNP 之间的显著上位性和联合效应。此外，与非肥胖对照组相比，肥胖受试者的人腹部脂肪组织中的 NOC mRNA 水平显著升高。
结论
NOC 基因的遗传变异与中国受试者的 BMI 相关。
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