Association of BMAL1 clock gene polymorphisms with fasting glucose in children

Abstract

Background The brain and muscle Arnt-like protein-1 (BMAL1) gene is an important circadian clock gene and previous studies have found that certain polymorphisms are associated with type 2 diabetes in adults. However, it remains unknown if such polymorphisms can affect fasting glucose in children and if other factors modify the associations. Methods A school-based cross-sectional study with 947 Chinese children was conducted. A multivariable linear regression model was used to analyze the association between BMAL1 gene polymorphisms and fasting glucose level. Results After adjusting for age, sex, body mass index (BMI), physical activity, and unhealthy diet, GG genotype carriers of BMAL1 rs3789327 had higher fasting glucose than AA/GA genotype carriers (b = 0.101, SE = 0.050, P = 0.045). Adjusting for the same confounders, rs3816358 was shown to be significantly associated with fasting glucose (b = 0.060, SE = 0.028, P = 0.032). Furthermore, a significant interaction between rs3789327 and nutritional status on fasting glucose was identified (Pinteraction = 0.009); rs3789327 was associated with fasting glucose in the overweight/obese subgroup (b = 0.353, SE = 0.126, P = 0.006), but not in non-overweight/non-obese children. Conclusions BMAL1 polymorphisms were significantly associated with the fasting glucose level in children. Additionally, the observed interaction between nutritional status and BMAL1 supports promoting an optimal BMI in children genetically predisposed to higher glucose level. Impact Polymorphisms in the essential circadian clock gene BMAL1 were associated with fasting blood glucose levels in children. Additionally, there was a significant interaction between nutritional status and BMAL1 affecting fasting glucose levels. BMAL1 rs3789327 was associated with fasting glucose only in overweight/obese children. This finding could bring novel insights into mechanisms by which nutritional status influences fasting glucose in children.

The circadian rhythm: an influential soundtrack in the diabetes story

“…Risk factors for developing metabolic syndrome (such as hypertension) are also associated to a SNP presented in the structure of neuronal PAS domain protein 2 (NPAS2), a paralog of CLOCK with the ability of binding to the BMAL1 ( 115 ). Bmal1 SNPs are associated with high blood pressure in addition to T2DM, hyperglycemia, and gestational diabetes ( 116 , 117 ). Patients with Cry2 and Per2 SNPs are prone to the glucose tolerance disorder, and individuals with Per2 SNPs, who overeat and experience stress-related eating, tend to acquire more weight ( 115 , 118 , 119 ).…”