Circadian rhythm of homocysteine is hCLOCK genotype dependent.

Homocysteine (Hcy) is known to be a prognostic marker for neurological, cardiovascular and cerebrovascular diseases and several other pathophysiological conditions. A sudden surge in Hcy can increase cardiovascular events. Hemodynamic modulations are known to be associated with individual's chronotype. Therefore, precise monitoring of Hcy is crucial for evaluating its impact on risk. The aim of the present study was to investigate the rhythmicity of Hcy under controlled dietary conditions and whether this rhythmicity is under the genetic control of circadian rhythm. Five subjects were selected from 200 Malayalam speaking healthy ethnic individuals who were screened for functionally critical variants of MTHFR and hCLOCK genes. MTHFR is the rate-limiting enzyme in the methionine cycle and critical for regulating Hcy levels while hCLOCK is a critical gene responsible in regulating the day and night cycles. Rhythmicity in Hcy levels were observed in all the subjects with a consensus on a morning nadir and an evening peak. Gender specific stratification of Hcy levels were observed among similar genotypes of MTHFR and hCLOCK genes. Variations from the conventional rhythmicity of Hcy were observed among similar genotypes of MTHFR and dissimilar hCLOCK genotypes. A reduced plasma Hcy in hCLOCK rs1801260 CC genotype individuals were observed in contrast to CT genotype individuals. The study tends to suggest that Hcy and body time are genetically interdependent and throws light on some of the previously unexplained reasons for variability in Hcy levels. A population specific variation of MTHFR and hCLOCK genes also highlights ethnicity specific risk management.