Differential Association of Uncoupling Protein 2 Polymorphisms with Pattern Identification among Korean Stroke Patients: A Diagnostic System in Traditional Korean Medicine

Uncoupling protein 2 (UCP2), a mitochondrial protein present in many organs and cell types, is known to dissipate the proton gradient formed by the electron transport chain. Its function is correlated with predictive parameters, such as obesity, diabetes, and metabolic syndromes. We analyzed the distribution of UCP2 polymorphisms in stroke patients diagnosed with one of the following four stroke subtypes based on the TKM standard pattern identification (PI): Qi-deficiency (QD), Dampness and Phlegm (D&P), Yin-deficiency (YD), and Fire and Heat (F&D). We studied a total of 1,786 stroke patients (397/QD, 645/D&P, 223/YD, and 522/F&D, 586/normal). Genotyping for the G-1957A, G-866A and A55V UCP2 polymorphisms was performed using the TaqMan. G-866A and A55V were significantly associated with the D&P and H&F subtypes. The frequency of subjects with the A allele of G-866A was significantly lower than the frequency of subjects with the GG type. The A55V polymorphism was also shown similar effect with G-866A in the dominant model. In contrast, no SNPs were shown to be associated with the QD or YD subtypes in this study. These results showed that the G-866A and A55V UCP2 polymorphisms may be genetic factors for specific PI types among Korean stroke patients.

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Clinical Approach to the Standardization of Oriental Medical Diagnostic Pattern Identification in Stroke Patients

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2011/768492 ◽

2011 ◽

Vol 2011 ◽

pp. 1-7 ◽

Cited By ~ 20

Author(s):

Han Jung Kim ◽

Hyung Sup Bae ◽

Seong Uk Park ◽

Sang Kwan Moon ◽

Jung Mi Park ◽

...

Keyword(s):

Regression Analysis ◽

Blood Stasis ◽

Diagnostic System ◽

Binary Logistic Regression ◽

Pattern Identification ◽

Binary Logistic Regression Analysis ◽

Clinical Approach ◽

Stroke Patients ◽

Logistic Equations ◽

Yin Deficiency

In Korea, many stroke patients receive oriental medical care, in which pattern-identification plays a major role. Pattern-identification is Oriental Medicine's unique diagnostic system. This study attempted to standardize oriental medical pattern-identification for stroke patients. This was a community-based multicenter study that enrolled stroke patients within 30 days after their ictus. We assessed the patients' general characteristics and symptoms related to pattern-identification. Each patient's pattern was determined when two doctors had the same opinion. To determine which variables affect the pattern-identification, binary logistic regression analysis was used with the backward method. A total of 806 stroke patients were enrolled. Among 480 patients who were identified as having a certain pattern, 100 patients exhibited the Fire Heat Pattern, 210 patients the Phlegm Dampness Pattern, nine patients the Blood Stasis Pattern, 110 patients the Qi Deficiency Pattern, and 51 patients the Yin Deficiency Pattern. After the regression analysis, the predictive logistic equations for the Fire Heat, Phlegm Dampness, Qi Deficiency, and Yin Deficiency patterns were determined. The Blood Stasis Pattern was omitted because the sample size was too small. Predictive logistic equations were suggested for four of the patterns. These criteria would be useful in determining each stroke patient's pattern in clinics. However, further studies with large samples are necessary to validate and confirm these criteria.

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Pattern Identifications for Stroke Patients admitted to National Rehabilitation Center using Korean Standard Pattern Identification for Stroke-III

Integrative Medicine Research ◽

10.1016/j.imr.2015.04.139 ◽

2015 ◽

Vol 4 (1) ◽

pp. 89

Author(s):

Chihyoung Son ◽

Jung Sup Lee ◽

Go Eun Lee

Keyword(s):

Pattern Identification ◽

Rehabilitation Center ◽

Stroke Patients ◽

Standard Pattern

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Nutritional manipulation between early to mid-gestation: effects on uncoupling protein-2, glucocorticoid sensitivity, IGF-I receptor and cell proliferation but not apoptosis in the ovine placenta

Reproduction ◽

10.1530/rep-06-0369 ◽

2007 ◽

Vol 134 (4) ◽

pp. 615-623 ◽

Cited By ~ 19

Author(s):

M G Gnanalingham ◽

P Williams ◽

V Wilson ◽

J Bispham ◽

M A Hyatt ◽

...

Keyword(s):

Cell Proliferation ◽

Uncoupling Protein ◽

Mitochondrial Protein ◽

Mrna Abundance ◽

Uncoupling Protein 2 ◽

Type I ◽

Voltage Dependent Anion Channel ◽

Glucocorticoid Sensitivity ◽

Ucp2 Mrna ◽

Glucocorticoid Action

In sheep, modest maternal nutrient restriction (NR) over the period of rapid placental growth restricts placentome growth and results in offspring in which glucocorticoid action is enhanced. Therefore, this study investigated the placental effects of early to mid-gestational NR on glucocorticoid receptor (GR), 11β-hydroxysteroid dehydrogenase type 2 (11βHSD2), uncoupling protein-2 (UCP2), and IGF type-I receptor (IGF-IR) mRNA abundance together with cell proliferation and apoptosis as determined histologically, and the mitochondrial proteins voltage-dependent anion channel and cytochrome c that are involved in apoptosis. Placenta was sampled at 80 and 140 days gestation (dGA; term ~147 dGA). NR was imposed between 28 and 80 days gestation when control and nutrient-restricted groups consumed 150 or 60% respectively of their total metabolizable energy requirements. All mothers were then fed to requirements up to term. Total fetal placentome weights were decreased by NR at 80 dGA but were heavier at 140 dGA following 60 days of nutritional rehabilitation. GR and UCP2 mRNA abundance increased whilst 11βHSD2 mRNA decreased with gestational age. NR persistently up-regulated GR and UCP2 mRNA abundance. 11βHSD2 mRNA was reduced by NR at 80 dGA but increased near to term. IGF-IRmRNA abundance was only decreased at 80 dGA. Placental apoptosis and mitochondrial protein abundance were unaffected by NR, whereas cell proliferation was markedly reduced. In conclusion, placental UCP2 and local glucocorticoid action are affected by the gestational nutritional status and may result in the offspring showing enhanced glucocorticoid sensitivity, thereby predisposing them to disease in later life.

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Uncoupling Protein 2 as a pathogenic determinant and therapeutic target in cardiovascular and metabolic diseases

Current Neuropharmacology ◽

10.2174/1570159x19666210421094204 ◽

2021 ◽

Vol 19 ◽

Author(s):

Rosita Stanzione ◽

Maurizio Forte ◽

Maria Cotugno ◽

Franca Bianchi ◽

Simona Marchitti ◽

...

Keyword(s):

Mitochondrial Membrane ◽

Metabolic Disorders ◽

Uncoupling Protein ◽

Heart Diseases ◽

Mitochondrial Protein ◽

Uncoupling Protein 2 ◽

Obesity And Diabetes ◽

Ucp2 Expression ◽

Increased Risk ◽

Wide Range

: Uncoupling protein 2 (UCP2) is a mitochondrial protein that acts as an anion carrier. It is involved in the regulation of several processes including mitochondrial membrane potential, generation of reactive oxygen species within the inner mitochondrial membrane and calcium homeostasis. UCP2 expression can be regulated at different levels: genetic (gene variants), transcriptional [by peroxisome proliferator-activated receptors (PPARs) and microRNAs], and post-translational. Experimental evidence indicates that activation of UCP2 expression through the AMPK/PPAR-α axis exerts a protective effect toward renal damage and stroke occurrence in an animal model of ischemic stroke (IS) associated with hypertension. UCP2 plays a key role in heart diseases (myocardial infarction and cardiac hypertrophy) and metabolic disorders (obesity and diabetes). In humans, UCP2 genetic variants (-866G/A and Ala55Val) associate with an increased risk of type 2 diabetes mellitus and of IS development. Over the last few years, many agents that modulate UCP2 expression have been identified. Some of them are natural compounds of plant origin such as Brassica oleracea, curcumin, berberine and resveratrol. Other molecules, currently used in clinical practice, include anti-diabetic (gliptin) and chemotherapeutic (doxorubicin and taxol) drugs. This evidence highlights the relevant role of UCP2 for the treatment of a wide range of diseases, which affect the national health systems of the Western countries. We will review current knowledge on the physiological and pathological implications of UCP2 with particular regard to cardiovascular and metabolic disorders and will focus on the available therapeutic approaches affecting UCP2 level for the treatment of human diseases.

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