A panel of rhythm gene polymorphisms is involved in susceptibility to type 2 diabetes mellitus and bipolar disorder

Biological rhythm is closely related to health. We aimed to identify the potential correlations of rhythm gene polymorphisms to type 2 diabetes mellitus (DM) or bipolar disorder (BD), which both have many abnormal rhythmic activities, in a sample of Chinese Han origin.

A total of 136 patients with BD, 166 patients with DM, and 130 healthy controls were collected. We screened 28 single nucleotide polymorphisms (SNPs) located in rhythm genes CLOCK, ARNTL, PER2, PER3, CRY1, and CRY2 respectively. Snapshot typing technology was used for genotyping.

Both the rs10832022-G and rs11022765-A allele frequencies of the ARNTL gene were significantly higher in patients with DM than in those with BD (corrected P=0.03, 0.004, respectively). The frequency of rs10832022-G, rs1022765-A, and rs11022762-T haplotypes, which was significantly lower in patients with BD than in controls (P=0.003, OR =0.579), was significantly higher in patients with DM than in those with BD (P=0.0002, OR =1.878). The rs2292910-CC genotypic frequency of the CRY2 gene was significantly higher in patients with BD than in controls (OR of regression =2.203, P=0.01), while the frequency of the AA genotype was significantly lower than in patients with DM (P=0.01). The frequency of rs1972874-G and rs36124720-G haplotype of the PER2 gene was significantly higher in patients with DM than in controls (P=0.01, OR =1.577).

Our study preliminarily suggested that both BD and type 2 DM could be considered as dysrhythmias with different rhythmic genetic backgrounds, which contribute to the early prediction of an individual's susceptibility to different rhythm disorders and early intervention.