Abstract

BackgroundPatients with stroke have various syndromes and symptoms. Through pattern identification (PI), traditional Korean medicine (TKM) classifies the several syndromes and symptoms of stroke patients into five categories: Fire-heat (FH), Dampness-phlegm (DP), Yin-deficiency (YD), Qi-deficiency (QD) and Blood-stasis (BS). DP has been associated with obesity and hyperlipidemia. Uncoupling protein-1 (UCP-1), which plays a major role in thermogenesis and energy expenditure can increase the risk of obesity and can be related metabolic disorders. In this study, we elucidated the association of three polymorphisms located in the UCP-1 promoter and coding region with DP among Korean stroke patients.Methods1,593 patients with cerebral infarction (583/DP, 1,010/non-DP) and 587 normal subjects were enrolled. The genotypes A-3826G, G-1766A and Ala64Thr (G+1068A) for each subject were determined by polymerase chain reaction with TaqMan probes and five percent of subjects were re-genotyped by sequencing method to confirm the accuracy of genotyping. The results were analyzed using a multiple logistic regression model to evaluate the genetic associations: the UCP-1polymorphisms of normal versus those of DP subjects and those of normal versus those of non-DP subjects.ResultsA significantly higher percentage of subjects in the DP group possessed the A-3826G G allele than the A allele (OR=1.508, p=0.006). Furthermore, the number of subjects with the GG type of A-1766G was significantly lower in the non-DP group than the normal group in the recessive model (OR=0.606, p=0.042). In addition, an analysis of the relationship among 2 SNPs of UCP-1 and lipid serum concentration showed that the serum level of HDL cholesterol was significantly higher in subjects with the A-3826G G allele in the normal group (p=0.032). Serum triglyceride and HDL cholesterol were also associated with the A-1766G variant in the recessive model (p=0.002, p=0.046).ConclusionsThese results suggest that that the A-3826G and A-1766G UCP-1 polymorphisms, which are related to obesity, might be candidate genetic markers for the DP pattern in the TKM diagnosis system.

Highlights

  • Patients with stroke have various syndromes and symptoms

  • The A1766G, which was found from Korean women, was related with body fat mass and abdominal fat, and haplotype (GAG) constructed by A-3826G, A-1766G and Ala64Thr was shown to be associated with less reduction of waist-hip ratio (WHR) and body fat mass than in non-carriers among Korea women [5,6,7]

  • The results showed that body characteristics values in DP group were significantly higher than those in normal group (p< 0.0001)

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Summary

Introduction

Patients with stroke have various syndromes and symptoms. Through pattern identification (PI), traditional Korean medicine (TKM) classifies the several syndromes and symptoms of stroke patients into five categories: Fire-heat (FH), Dampness-phlegm (DP), Yin-deficiency (YD), Qi-deficiency (QD) and Blood-stasis (BS). Uncoupling protein-1 (UCP-1), which plays a major role in thermogenesis and energy expenditure can increase the risk of obesity and can be related metabolic disorders. We elucidated the association of three polymorphisms located in the UCP-1 promoter and coding region with DP among Korean stroke patients. UCP-1 plays important roles in energy homeostasis, and UCP-1 gene polymorphisms have been implicated in the pathogenesis of obesity and related metabolic disorders, including lipid disorders [3,4]. The G allele of A-3826G was reported to be associated with higher body fat gain, increased BMI, and reduced postprandial thermogenesis by Nagai et al and Oppert et al [4,5] and known to be related with resistance against diet-induced weight loss, reduced resting energy expenditure (REE) in young women, reinforcing the metabolic action of BAT and its effect on resting energy balance in adults [6]. The Ala64Thr (G+1068A) is known to be associated with increased WHR among Caucasians as well as lower fat content and WHR [8]

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