Molecular basis for cold-intolerant yang-deficient constitution of traditional Chinese medicine

Based on the theory of constitution of Traditional Chinese Medicine (TCM), the human population can be classified into nine constitutions including a balanced constitution and eight unbalanced constitutions (Yang-deficient, Yin-deficient, Qi-deficient, Phlegm-wetness, Wetness-heat, Stagnant blood, Depressed, and Inherited special constitutions). Generally, unbalanced constitutions are more susceptible to certain diseases than balanced constitutions. However, whether such constitution classification has modern genetic and biochemical basis is poorly understood. Here we examined gene expression profiles in peripheral white blood cells from eight individuals with Yang-deficient constitutions and six individuals with balanced constitutions using Affymetrix U133 plus 2.0 expression array. Based on a q < 0.05 and fold-change > or = 2 cutoff, we have identified that 785 genes are up-regulated and 954 genes are down-regulated in Yang-deficient constitution compared to a balanced constitution. Importantly, we found that the expression of thyroid hormone receptor beta (TRbeta) and several key nuclear receptor coactivators including steroid receptor coactivator 1 (SRC1), steroid receptor coactivator 3 (SRC3), cAMP-response element-binding protein (CREB) binding protein (CBP) and Mediator is significantly decreased. Such decreased expression of TR transcription complex may lead to impaired thermogenesis, providing a molecular explanation of the main symptom associated with Yang-deficient constitution, cold intolerance. Future studies are needed to validate these gene expression changes in additional populations and address the underlying mechanisms for differential gene expression.