A recent study published by Kim et al. explained that dampness-phlegm is an impediment to Qi, energy that circulates in channels called meridians and that causes various symptoms and signs when blocked or disrupted because of its high turbidity, heaviness, stickiness, and downward flowing properties
[12, 19]. In addition, DP was related to clinical indicators, such as overweight, pale tongue, and slippery pulse
. In TKM, DP has long been a suspected as a cause for obesity. Dong-eui-bo-gam, which are the most extensively read medical texts by TKM doctors and are praised as one of the most important medical texts in TKM
, declared dampness-phlegm as a main factor of obesity, stating that overweight people have an abnormal biomechanical flow and that the Qi deficiency generates cold, cold generates dampness, and dampness generates phlegm, which finally leads to obesity
. Recently, there have been several scientific attempts to verify the relationship between DP and obesity. The study of the relationship of DP tongue diagnosis to hyperlipidemia in stroke suggests that serum lipid levels, such as total cholesterol, HDL cholesterol, and triglyceride, were higher in the DP group than those in the non-DP group
. In addition, Min et al. reported that TC, BMI and waist circumference were significantly increased in DP patients
. A case–control study of the relationship of DP and blood lipid levels revealed that DP was significantly correlated with increased LDL cholesterol and was an independent predictor of hyperlipoproteinemia
. However, few studies using a genetic analysis to prove the relationship between DP and obesity have been carried out up to now. An analysis on obesity-related genotype can provide a significant insight to present scientific evidence including a number of clinical trials that show the relationship between DP and obesity. UCP-1 is a major obesity-related gene that regulates energy homeostasis inside body
. When exposed to coldness, the expression of UCP-1 is promoted by adaptive thermogenesis, that is, heat generation consuming pH-gradient induced by oxidative phospholyation and by increased adrenergic stimulation, β3-agonists, retinoids, thyroid hormone, PPARγ ligand and leptin
However, the inhibition of gene expression or gene activity caused by genetic deficiency of UCP-1 may result in imbalance on heat generation inside body, which changes in the oxidation of free fatty acids in the mitochondria can alter the blood levels of lipids through tissue cholesterol transport and ultimately lead to obesity. Therefore, this mechanism to control blood lipids may be affected by genetic polymorphisms such as A-3826G polymorphism of UCP-1 gene
. This was proved by a study that showed lowered activation of sympathetic nerve and declined expression of UCP-1 in BAT of obese rats and by another in vivo study that reported overexpression of UCP-1 reduced degree of obesity induced by high fat diet. This signifies the acceleration of energy consumption by the expression of UCP-1 is effective to the prevention and suppression of obesity
The A-3826G, A-1766G and Ala64Thr, polymorphisms of UCP-1 gene, were previously associated with weight loss, abdominal obesity and metabolic disorder, which are risk factors of stroke. In the current study, we examined that A-3826G SNP were significantly associated with DP among Korean stroke patients. The G allele frequency of A-3826G was significantly higher than the A allele in the DP group (p=0.0247), and the number of subjects with the GG or GA genotype was larger than those with the AA type. A large distribution of G allele revealed after the analysis on A-3826G polymorphism among the patients with DP is also found among the obese
. Considering DP acts as a causative factor of obesity in TKM, and UCP-1 is regulator of obesity, DP and UCP-1 seem to be highly associated each other. Investigating the genetic polymorphic distribution is meaningful to predict and diagnose obesity.
Oberkoflr et al. reported that UCP-1 mRNA levels in visceral fat were lower in obese subjects and that UCP-1 mRNA levels in fat tissue were regulated by the UCP-1 genotype
[31, 32]. This result may have been observed because the G allele carrier of A-3826G in UCP-1 regulated by the extent of obesity may have reduced expression, which causes less energy dissipation as heat.
This study has several limitations. The first limitation relates to the diagnostic standard for PI. The PI types were confirmed by two experts with sufficient clinical experiences. Nevertheless, their diagnoses did not match. PI still has limitations in consistency and reproducibility because of its high dependence on subjective diagnostic indicators. Second, although DP in TKM is generally considered as a major causative factor for obesity, DP is not the sole cause that induces obesity, and other pattern such as Fire-Heat has also potential to result in obesity
. Third, sample size was not enough to generalize the association between UCP-1 polymorphisms and DP. Especially, the number of subjects in normal group was smaller than that of the patients group. Thus, a further study to confirm the association will be needed.
We already reported that polymorphisms of the PON1 and NPY genes, which were associated with stroke and obesity, were related to DP among Korean stroke patients. The results of this study replicate the relationship that other studies have found between genetic polymorphism and PI, and the A-3826G SNP of the UCP-1 gene might be a predictive genetic marker for DP pattern.