OS 33-09 ASSOCIATION OF CLOCK GENE POLYMORPHISM WITH INSULIN RESISTANCE IN HYPERTENSION: A CASE-CONTROL STUDY.

OBJECTIVE: Circadian rhythm disruption is shown to be the cause of various health disorders. CLOCK and BMAL1, two core circadian transcription factors, were associated with the regulation of glucose homeostasis. This study evaluated the association between single nucleotide polymorphisms in CLOCK and BMAL1 gene and insulin resistance (IR) in hypertensive patients.

DESIGN AND METHOD: We collected 334 outpatients with essential hypertension (EH), who have not taken any antihypertensive agents or stopped the medications for at least a week for this case-control study. The value of homeostasis model assessment of insulin resistance (HOMA-IR) more than 2.69 was considered as IR positive. Clock T3111C & Bmal1 A1420G genotypes were determined by PCR and automated DNA sequencer using peripheral blood DNA as a template.

RESULTS: A total of 334 patients were analyzed (103 in the HOMA-IR positive group and 231 in the HOMA-IR negative group). Compared with the negative group, waist circumference, body mass index, HbA1C, total cholesterol, triglyceride and plasminogen activator inhibitor-1 were significantly increased, while HDL-C was significantly decreased in the HOMA-IR positive group (P < 0.05-0.001). The results of 24-h ambulatory blood pressure (BP) monitoring showed that 24-h mean systolic BP, especially the night systolic BP was higher in the HOMA-IR positive group (P < 0.05). Notably, the distribution frequency of the C allele of Clock T3111C and the GG genotype of Bmal1 A1420G were significantly higher in the HOMA-IR positive group (29.1vs 10.8%, p < 0.000 and 43.7vs 27.7%, p = 0.007). We found a strong association between the absence of the C allele of Clock T3111C (odds ratio [OR] = 4.128, CI 95% 2.313-7.368, p = 0.000), as well as the GG genotype of Bmal1 A1420G (OR = 1.983, CI 95% 1.117-3.521, p = 0.019), and the increased HOMA-IR in Chinese EH patients.

CONCLUSIONS: Hypertensive patients with the C allele of Clock T3111C or the GG genotype of Bmal1 A1420G might be susceptibility to IR, which could be associated with higher night SBP.