Polymorphism Of Uncoupling Protein Research Articles

Effect of maternal pregestational diabetes mellitus on congenital heart diseases.

The increasing population of diabetes mellitus in adolescent girls and women of childbearing age contributes to a large number of pregnancies with maternal pregestational diabetes mellitus. Congenital heart diseases are a common adverse outcome in mothers with pregestational diabetes mellitus. However, there is little systematic information between maternal pregestational diabetes mellitus and congenital heart diseases in the offspring. Literature selection was performed in PubMed. One hundred and seven papers were cited in our review, including 36 clinical studies, 26 experimental studies, 31 reviews, eight meta-analysis articles, and six of other types. Maternal pregestational diabetes mellitus poses a high risk of congenital heart diseases in the offspring and causes variety of phenotypes of congenital heart diseases. Factors such as persistent maternal hyperglycemia, oxidative stress, polymorphism of uncoupling protein 2, polymorphism of adiponectin gene, Notch 1 pathway, Nkx2.5 disorders, dysregulation of the hypoxia-inducible factor 1, and viral etiologies are associated with the occurrence of congenital heart diseases in the offspring of mothers with pregestational diabetes mellitus. Treatment options including blood sugar-reducing, anti-oxidative stress drug supplements and exercise can help to prevent maternal pregestational diabetes mellitus from inducing congenital heart diseases. Our review contributes to a better understanding of the association between maternal pregestational diabetes mellitus and congenital heart diseases in the offspring and to a profound thought of the mechanism, preventive and therapeutic measurements of congenital heart diseases caused by maternal pregestational diabetes mellitus.

Effect of -55C/T Polymorphism of Uncoupling Protein 3 Gene on Risk for New-Onset Diabetes in Chinese Peritoneal Dialysis Patients: A Prospective Cohort Study

Background: A high-glucose load in therapy can cause new-onset diabetes (NOD) in peritoneal dialysis (PD) patients. Genetic variability may result in risk modulation. Objectives: This study aims to investigate the association between −55C/T polymorphism of uncoupling protein 3 (UCP3) gene and the risk of NOD in PD patients. Methods: Nondiabetic incident PD patients between May 2005 and January 2017 were recruited (n = 154). −55C/T polymorphism of the UCP3 was genotyped in all participants at baseline. The cohort of wild group (−55CC) and mutant group (−55CT or −55TT) was built based on the genotypic difference. Insulin resistance was evaluated by the homeostasis model assessment method (HOMA-IR) during the follow-up. Binary logistic regression was performed to explore the association between HOMA-IR and genotypes. Competitive risk analysis was used to analyze the impact of −55C/T polymorphism of UCP3 on risk for NOD. Results: The cohort was followed for up to 164.6 months (median: 58.3 months; interquartile range: 30.7 months). During the follow-up, 14 NODs occurred in the mutant group, while only 3 occurred in the wild group. Patients in the mutant group had higher HOMA-IR (Odd ratio: 2.210; 95% CI: 1.043–4.680; p = 0.038). Genotype with the variant T allele turned out to be an independent predictor for NOD morbidity (HR: 7.639; 95% CI: 1.798–32.451; p = 0.006). Conclusions: The variant of T allele of UCP3 −55C/T polymorphism was an independent predictor for NOD in PD patients. Early identification of the genotype may provide scientific basis for patients’ clinic management.

UCP2 and PPARG gene polymorphisms and their association with milk yield and composition traits in goats

Abstract With the present study, we aimed to identify polymorphisms in the genes encoding mitochondrial uncoupling protein 2 (UCP2) and peroxisome proliferator-activated receptor gamma (PPARG), and to evaluate their associations with breeding values for milk production and composition traits in goats. Breeding values were estimated from milk yield and composition data of Saanen and Alpine animals using a single-trait model. The number of animals used for the estimation of breeding values ranged from 1,094 to 1,292, depending on the trait studied. After identification of the polymorphisms, the animals were genotyped for association analysis. Among animals with estimated breeding values, we randomly genotyped 185 for the UCP2.29614171G/A polymorphism located in the promoter region of the UCP2 gene, 176 for the UCP2.29615319G/A polymorphism located in exon 2 of the UCP2 gene, and 194 for the PPARG-A/B polymorphism located in the promoter region of the PPARG gene. For the UCP2 gene, the UCP2.29614171G/A polymorphism showed association (P

Association of UCP1 polymorphisms with type 2 diabetes mellitus and their interaction with physical activity and sedentary behavior.

Uncoupling protein 1 (UCP1) has been reported to be associated with type 2 diabetes mellitus (T2DM) in different populations, however, little is reported in Chinese population. The present study aimed to explore the association between some polymorphisms of UCP1 with T2DM and the interactions between UCP1 and physical activity/sedentary behavior (PA/SB) lifestyle in Chinese population. Three polymorphisms (rs1472268, rs3811790 and rs3811791) were genotyped in 929 T2DM patients and 1044 nondiabetic controls. The data of PA and SB were acquired. Logistic regression and linear regression were conducted to assess the association of UCP1 and T2DM and related traits. The CC genotype of rs3811791 was significantly associated with an increased risk of T2DM [odds ratio (OR)=1.42, P=0.042] and a higher level of triglyceride (TG) (β=0.048, P=0.034). This association still existed in the group of SB≥3h/d (OR=1.66, P=0.009) and the group of PA≥150min/week and SB≥3h/d (OR=1.60, P=0.034). In the group of PA<150min/week and SB<3h/d, CC genotype was associated with a higher level of homeostatic model assessment of insulin resistance (HOMA-IR) index, and in the group of PA<150min/week and SB≥3h/d, CC genotype was associated with increased level of TG and decreased high-density lipoprotein cholesterol (HDL-C). This study suggests that rs3811791 of UCP1 may be associated with T2DM and TG. Moreover, we demonstrate that SB interacted with rs3811791 of UCP1 was associated with T2DM, and PA interacted with rs3811791 of UCP1 was associated with the level of HOMA-IR, HDL-C, and TG.

-866G/A and Ins/Del polymorphisms in the UCP2 gene and diabetic kidney disease: case-control study and meta-analysis.

Uncoupling protein 2 (UCP2) decreases reactive oxygen species (ROS). ROS overproduction is a key contributor to the pathogenesis of diabetic kidney disease (DKD). Thus, UCP2 polymorphisms are candidate risk factors for DKD; however, their associations with this complication are still inconclusive. Here, we describe a case-control study and a meta-analysis conducted to investigate the association between UCP2 -866G/A and Ins/Del polymorphisms and DKD. The case-control study comprised 385 patients with type 1 diabetes mellitus (T1DM): 223 patients without DKD and 162 with DKD. UCP2 -866G/A (rs659366) and Ins/Del polymorphisms were genotyped by real-time PCR and conventional PCR, respectively. For the meta-analysis, a literature search was conducted to identify all studies that investigated associations between UCP2 polymorphisms and DKD in patients with T1DM or type 2 diabetes mellitus. Pooled odds ratios were calculated for different inheritance models. Allele and genotype frequencies of -866G/A and Ins/Del polymorphisms did not differ between T1DM case and control groups. Haplotype frequencies were also similar between groups. Four studies plus the present one were eligible for inclusion in the meta-analysis. In agreement with case-control data, the meta-analysis results showed that the -866G/A and Ins/Del polymorphisms were not associated with DKD. In conclusion, our case-control and meta-analysis studies did not indicate an association between the analyzed UCP2 polymorphisms and DKD.

The -866G/A polymorphism in the promoter of the UCP2 gene is associated with risk for type 2 diabetes and with decreased insulin levels

Background and aimOxidative stress and impaired insulin secretion is an underlying major risk factor for the development of type 2 diabetes (T2D). Uncoupling protein-2 (UCP2) is involved in the regulation of reactive oxygen species production, insulin secretion, and lipid metabolism. Based on this we aimed to find an association of UCP2 (G-866A) polymorphism with the risk of T2D in South Indian population. MethodsA total of 318 T2D patients and 312 controls were enrolled in this study. All the study subjects were genotyped for UCP2 (G-866A) polymorphism using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Fasting blood glucose, HbA1c, serum lipid profile, systolic and diastolic blood pressure were measured by standard biochemical methods. Fasting serum insulin level was measured by ELISA. ResultsIn UCP2 (G-866A) polymorphism, the distribution of GA (46%) and AA (14%) genotypes were significantly higher in T2D patients than the healthy controls. The frequency of GA and AA genotypes have high risk towards the development of T2D with an Odds Ratio (OR) of 1.55 (P = 0.01) and 2.04 (P = 0.01) respectively. Moreover, SNP-866 G>A allele was found to be significantly associated with T2D (OR = 1.48, P = 0.001, 95% CI = 1.16–1.88). Further, the UCP2 AA genotype showed significantly decreased level of insulin by the reduction in pancreatic β-cell function in T2D patients. ConclusionUCP2 (G-866A) polymorphism may play a crucial role in the pathogenesis of insulin secretion thus leads to the development of T2D.

Association of Uncoupling Protein 1 (UCP1) gene polymorphism with obesity: a case-control study

BackgroundObesity is one of the main causes of morbidity and mortality worldwide. More than 120 genes have been shown to be associated with obesity related phenotypes. The aim of this study was to determine the effect of selected genetic polymorphisms in Uncoupling protein 1 (UCP1) and Niemann-Pick C1 (NPC1) genes in an obese population in Saudi Arabia.MethodsThe genotypes of rs1800592, rs10011540 and rs3811791 (UCP1 gene) and rs1805081 and rs1805082 (NPC1 gene) were determined in a total of 492 subjects using TaqMan chemistry by Real-time PCR. In addition, capillary sequencing assay was performed to identify two specific polymorphisms viz., rs45539933 (exon 2) and rs2270565 (exon 5) of UCP1 gene.ResultsA significant association of UCP1 polymorphisms rs1800592 [OR, 1.52 (1.10–2.08); p = 0.009] was observed in the obese cohort after adjusting with age, sex and type 2 diabetes. Further BMI based stratification revealed that this association was inconsistent with both moderate and extreme obese cohort. A significant association of UCP1 polymorphisms rs3811791 was observed only in the moderate-obese cohort [OR = 2.89 (1.33–6.25); p = 0.007] but not in the extreme-obese cohort indicating an overlying genetic complexity between moderate-obesity and extreme-obesity. The risk allele frequencies, which were higher in moderate-obese cohort, had abnormal HDL, LDL and triglyceride levels.ConclusionThe rs1800592 and rs3811791 of UCP1 gene are associated with obesity in general and in the moderate-obese group in particular. The associated UCP1 polymorphisms in the moderate-obese group may regulate the impaired energy metabolism which plays a significant role in the initial stages of obesity.

Uncoupling Protein 2 and Peroxisome Proliferator-Activated Receptor γ Gene Polymorphisms in Association with Diabetes Susceptibility in Chinese Han Population with Variant Glucose Tolerance.

Objective To investigate the association of polymorphisms in uncoupling protein 2 (UCP2) and peroxisome proliferator-activated receptor (PPARγ) with glucolipid metabolism in Chinese Han population. Methods Five hundred eighty-nine subjects were divided into normal glucose tolerance (NGT) group (n = 198) and abnormal glucose tolerance group (n = 358). HbA1c, blood lipid profile, plasma glucose, and insulin were determined. Insulin sensitivity (HOMA-IR and Matsuda index (ISIM)) and insulin secretion indexes (HOMA-β, early and total phase disposition index) were evaluated. Eight potential functional SNPs in UCP2 and 7 in PPARγ were selected. SNPs were genotyped on Sequenom MassARRAY platform. Results The GG genotype of rs2920502 in PPARγ was associated with decreased risk of impaired glucose tolerance (G allele: OR: 0.818, 95%CI: 0.526–0.969, P = 0.042; GG: OR: 0.715, 95%CI: 0.527–0.97, P = 0.031). The TT genotype of rs3856806 in PPARγ was associated with increased risk of impaired glucose tolerance (T allele: OR: 1.46, 95%CI: 1.055–2.017, P = 0.022; TT: OR: 1.58, 95%CI: 1.104–2.761, P = 0.032). The GG genotype of rs2920502 in PPARγ had better blood glucose and increased insulin secretion and had lower HOMA-IR than GC/CC genotypes. Conclusion It probably could prevent insulin resistance in early stage by classifying the genotype of rs649446 and rs7109266 in UCP2. The GG genotype of rs2920502 in PPARγ had a decreased risk for diabetes. The TT genotype of rs3856806 in PPARγ had an increased risk for diabetes.

Uncoupling protein 2 haplotype does not affect human brain structure and function in a sample of community-dwelling older adults.

Uncoupling protein 2 (UCP2) is a mitochondrial membrane protein that plays a role in uncoupling electron transport from adenosine triphosphate (ATP) formation. Polymorphisms of the UCP2 gene in humans affect protein expression and function and have been linked to survival into old age. Since UCP2 is expressed in several brain regions, we investigated in this study whether UCP2 polymorphisms might 1) affect occurrence of neurodegenerative or mental health disorders and 2) affect measures of brain structure and function. We used structural magnetic resonance imaging (MRI), diffusion-weighted MRI and resting-state functional MRI in the neuroimaging sub-study of the Whitehall II cohort. Data from 536 individuals aged 60 to 83 years were analyzed. No association of UCP2 polymorphisms with the occurrence of neurodegenerative disorders or grey and white matter structure or resting-state functional connectivity was observed. However, there was a significant effect on occurrence of mood disorders in men with the minor alleles of -866G>A (rs659366) and Ala55Val (rs660339)) being associated with increasing odds of lifetime occurrence of mood disorders in a dose dependent manner. This result was not accompanied by effects of UCP2 polymorphisms on brain structure and function, which might either indicate that the sample investigated here was too small and underpowered to find any significant effects, or that potential effects of UCP2 polymorphisms on the brain are too subtle to be picked up by any of the neuroimaging measures used.

Association of UCP2 -866G>A Polymorphism With Nonalcoholic Fatty Liver Disease in Patients From North-West of Iran.

To investigate the association of uncoupling protein-2 (UCP2) -866G > A gene polymorphism (rs659366) with nonalcoholic fatty liver disease (NAFLD). We performed a case-control study with a cohort of 75 patients with NAFLD (of Iranian ethnicity) and 76 healthy individuals of Iranian ethnicity. The UCP2 -866G > A polymorphism (rs659366) was determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Patients with AA and AG genotypes were 71% and 68%, respectively, more likely to have NAFLD, compared with individuals with the GG genotype (reference group). In subjects with a GG genotype, serum triglyceride (TG) concentration was significantly higher in patients with NAFLD (P = .04). Serum alanine aminotransferase (ALT) concentrations in all 3 genotypes and serum aspartate aminotransferase (AST) concentrations in AG and GG genotypes of UCP2 gene polymorphism were significantly higher in patients (P <.05). Our results revealed a modest modifier effect of -866G>A UCP2 polymorphism in patients with NAFLD.

Interactions between UCP2 SNPs and telomere length exist in the absence of diabetes or pre-diabetes.

Mitochondrial uncoupling protein 2 (UCP2) can affect oxidative stress levels. UCP2 polymorphisms are associated with leukocyte telomere length (LTL) in Type 2 Diabetes, which also induces considerable background oxidative stress. The effects of UCP2 polymorphisms on LTL in populations without diabetes have not been well described. Our aims are to evaluate the interaction between LTL and UCP2 polymorphisms in 950 subjects without diabetes. The monochrome multiplex quantitative PCR method was used to measure relative LTL. Taqman SNP genotyping assay was applied to genotypes for UCP2 rs659366 and rs660339. We found shorter LTL associated with increased age (P < 0.001) and triglyceride levels (P = 0.041). After adjustment for cardiovascular risk factors, rs659336 GG genotype carriers demonstrated a shorter LTL (1.257 ± 0.186), compared to GA carriers (1.288 ± 0.230, P = 0.022) and AA carriers (1.314 ± 0.253, P = 0.002). LTL was shorter in the CC rs660339 genotype (1.254 ± 0.187) compared to TT (1.297 ± 0.242, P = 0.007) and CT carriers (1.292 ± 0.229, P = 0.016). The T allele of rs660339 is associated with a longer LTL of approximately 0.04 compared to CC homozygotes. Thus, UCP2 rs659366 A allele and rs660339 T allele are both related to longer LTL in subjects without diabetes, independent of cardiovascular risk factors.

ACE and UCP2 gene polymorphisms and their association with baseline and exercise-related changes in the functional performance of older adults

Maintaining high levels of physical function is an important aspect of successful ageing. While muscle mass and strength contribute to functional performance in older adults, little is known about the possible genetic basis for the heterogeneity of physical function in older adults and in how older adults respond to exercise. Two genes that have possible roles in determining levels of muscle mass, strength and function in young and older adults are angiotensin-converting enzyme (ACE) and mitochondrial uncoupling protein 2 (UCP2). This study examined whether polymorphisms in these two individual genes were associated with baseline functional performance levels and/or the training-related changes following exercise in previously untrained older adults. Five-eight Caucasian older adults (mean age 69.8 years) with no recent history of resistance training enrolled in a 12 week program of resistance, balance and cardiovascular exercises aimed at improving functional performance. Performance in 6 functional tasks was recorded at baseline and after 12 weeks. Genomic DNA was assayed for the ACE intron 16 insertion/deletion (I/D) and the UCP2 G-866A polymorphism. Baseline differences among genotype groups were tested using analysis of variance. Genotype differences in absolute and relative changes in physical function among the exercisers were tested using a general linear model, adjusting for age and gender. The genotype frequencies for each of the studied polymorphisms conformed to the Hardy-Weinberg equilibrium. The ACE I/D genotype was significantly associated with mean baseline measures of handgrip strength (II 30.9 ± 3.01 v. ID 31.7 ± 1.48 v. DD 29.3 ± 2.18 kg, p < 0.001), 8ft Up and Go time (II 6.45 ± 0.48 v. ID/DD 4.41 ± 0.19 s, p < 0.001) and 6 min walk distance (II 458 ± 28.7 v. ID/DD 546 ± 12.1m, p = 0.008). The UCP2 G-866A genotype was also associated with baseline 8ft Up and Go time (GG 5.45 ± 0.35 v. GA 4.47 ± 0.26 v. AA 3.89 ± 0.71 s, p = 0.045). After 12 weeks of training, a significant difference between UCP2 G-886A genotype groups for change in 8ft Up and Go time was detected (GG −0.68 ± 0.17 v. GA −0.10 ± 0.14 v. AA +0.05 ± 0.31 s, p = 0.023). While several interesting and possibly consistent associations with older adults’ baseline functional performance were found for the ACE and UCP2 polymorphisms, we found no strong evidence of genetic associations with exercise responses in this study. The relative equivalence of some of these training-response findings to the literature may have reflected the current study’s focus on physical function rather than just strength, the relatively high levels of baseline function for some genotype groups as well as the greater statistical power for detecting baseline differences than the training-related changes.

Effect of the beta-3 adrenergic receptor Trp64Arg and uncoupling protein 1-3826 A>G genotypes on lipid and apolipoprotein levels in overweight/obese and non-obese Chinese subjects.

BackgroundThe beta-3 adrenergic receptor (β3-AR) Trp64Arg and uncoupling protein 1 (UCP1) -3826 A > G polymorphisms have been reported to be associated with obesity and/or lipid metabolism in some populations. This study examined the possible association of the β3-AR and UCP1 polymorphisms with overweight/obesity or lipid variation in a Southwest Chinese population.MethodsA total of 418 Han Chinese (249 overweight/obese and 169 healthy control subjects) in the Chengdu area were studied using PCR-RFLP analysis. Total serum cholesterol (TC) and triglycerides (TGs) were measured using an enzymatic method. High density lipoprotein cholesterol (HDL-C) was determined after sodium phosphotungstate/magnesium chloride precipitation of low-density lipoproteins by polyvinyl sulfate. Serum apolipoproteins were quantified by radial immunodiffusion.ResultsThe genotype and allele frequencies of the β3-AR Trp64Arg and UCP1 -3826 A > G polymorphisms in overweight/obese subjects exhibited no significant differences compared to the controls. However, subjects carrying the β3-AR TrpTrp genotype and UCP1 AG genotype had higher TG levels than those carrying the Arg allele and AA genotype, respectively (P < 0.05), while controls carrying the β3-AR Arg allele had significantly higher TC and apo AII concentrations than those carrying the TrpTrp genotype (P < 0.05). Additionally, subjects carrying the UCP1 AG genotype exhibited elevated apo C-II and apo C-III levels compared to those carrying the AA genotype (P < 0.05). We were unable to find an association of the UCP1 and β3-AR polymorphisms with low HDL-cholesterolemia in the overweight/obese subjects.ConclusionsThe present study provides evidence that the β3-AR Trp64Arg and UCP1 -3826 A > G polymorphisms are associated with TG levels in overweight/obese Chinese subjects and that the two polymorphisms are also associated with certain lipid and apolipoprotein variations, depending on BMI. However, these polymorphisms are not associated with overweight/obesity or low HDL-cholesterolemia in a Chinese population from the Chengdu area.

Correlations among obesity-associated gene polymorphisms, body composition, and physical activity in patients with type 2 diabetes mellitus.

Context:Various studies have focused on the correlation between β2-adrenergic receptor (β2AR), the β3-adrenergic receptor (β3AR), and the uncoupling protein 1 (UCP1) polymorphisms and obesity in patients with type 2 diabetes mellitus (T2DM).Aims:We examined the correlation between these polymorphisms and body composition variables and between body composition and lifestyle variables in Japanese T2DM patients.Materials and Methods:Of the 48, T2DM outpatients in Kanagawa prefecture recruited for participation, 32 (6 men and 26 women) met the study criteria and were enrolled. Obesity-related gene polymorphisms were identified in 3 genes β3AR, UCP1, and β2AR using the SMart amplification process. Body composition variables were measured using a body composition analyzer. Data regarding food and nutrient consumption, family history, and lifestyle factors were collected via administration of questionnaires.Results:Because significant differences in body composition variables were found between men and women, statistical analysis was performed with data from the 25 female subjects only. On the basis of results of genetic testing, the subjects were divided into genotype groups for two-group and three-group comparison. The β3AR, UCP1, and β2AR polymorphisms and body composition significantly correlated with the percentage of subcutaneous fat in both arms as compared with the wild type or hetero groups with β3AR polymorphisms. However, physical activity correlated with several body composition variables.Conclusions:These results suggest that obesity in T2DM patients is not the result of presence of an obesity-related gene polymorphism but rather the absence of daily physical activity.

The genetic association study between polymorphisms in uncoupling protein 2 and uncoupling protein 3 and metabolic data in dogs.

BackgroundThe uncoupling proteins (UCPs) in the mitochondrial inner membrane are members of the mitochondrial anion carrier protein family that play an important role in energy homeostasis. Genetic association studies have shown that human UCP2 and UCP3 variants (SNPs and indels) are associated with obesity, insulin resistance, type 2 diabetes mellitus, and metabolic syndrome. The aim of this study was to examine the genetic association between polymorphisms in UCP2 and UCP3 and metabolic data in dogs.ResultsWe identified 10 SNPs (9 intronic and 1 exonic) and 4 indels (intronic) in UCP2, and 13 SNPs (11 intronic and 2 exonic) and one indel (exonic) in UCP3, by DNA sequence analysis of 11 different dog breeds (n = 119). An association study between these UCP2 and UCP3 variants and the biochemical parameters of glucose, total cholesterol, lactate dehydrogenase and triglyceride in Labrador Retrievers (n = 50) showed that none of the UCP2 polymorphisms were significantly associated with the levels of these parameters. However, four UCP3 SNPs (intron 1) were significantly associated with total cholesterol levels. In addition, the allele frequencies of two of the four SNPs associated with higher total cholesterol levels in a breed that is susceptible to hypercholesterolemia (Shetland Sheepdogs, n = 30), compared with the control breed (Shiba, n = 30).ConclusionThe results obtained from a limited number of individuals suggest that the UCP3 gene in dogs may be associated with total cholesterol levels. The examination of larger sample sizes and further analysis will lead to increased precision of these results.Electronic supplementary materialThe online version of this article (doi:10.1186/1756-0500-7-904) contains supplementary material, which is available to authorized users.

A 45-bp insertion/deletion polymorphism of UCP2 gene is associated with metabolic syndrome

BackgroundMetabolic syndrome (MeS) is being recognized as a risk factor for insulin resistance and cardiovascular disease. The present study was aimed to find out the possible association between 45-bp I/D polymorphism of uncoupling protein 2 (UCP2) and MeS.MethodsDNA was extracted from peripheral blood of 151 subjects with and 149 subjects without MeS. 45-bp I/D variant of UCP2 was detected using polymerase chain reaction (PCR).ResultsOur finding showed that 45-bp I/D polymorphism was associated with protection against MeS (OR = 0.56, 95% CI = 0.34-0.92, p = 0.020 D/I vs DD and OR = 0.54, 95% CI = 0.34-0.86, p = 0.009; D/I + I/I vs D/D). The I allele decreased the risk of MeS (OR = 0.62, 95% CI = 0.44-0.90, p = 0.011) in comparison with D allele.ConclusionIn conclusion, our result suggests that 45-bp I/D polymorphism is associated with the risk of MeS, which remains to be cleared.

UCP2 and UCP3 polymorphisms as risk factors of insulin resistance for Indonesian obese adolescents

Uncoupling Protein 2 (UCP2) dan Uncoupling Protein 3 (UCP3) is a mitochondrial transmembrane carriers which uncouple the transport of protons across the inner mitochondrial membrane from electron transport and the synthesis of ATP from ADP. The UCPs play a role in energy homeostasis and have considered to be candidate gene for controlling obesity and insulin resistance. The aim of our study is to analyze UCP2 and UCP3 polymorphisms as risk factors of insulin resistance in obese adoslescent. A case control study was conducted in Junior High School in Semarang, Central Java, Indonesia during 2007- 2008. Seventy five subjects included in this study. Height, weight and body mass index (BMI) were measured. Insulin resistance was estimated by using the homeostasis model assessment (HOMA-IR) score which calculated as fasting insulin (microU/mL) x fasting glucose (mmol/L)/22.5. Three polymorphic sites i.e. UCP3 -55c/t, UCP3 Y210Y, and UCP2 A55V were investigated by using the Restriction Length Fragment Polymorphism. The data were analyzed by 2x2 table and odd rasio with 95% confidence interval. There were 38 obese (27 male, 11 female) and 37 normoweight ( 25 male, 12 female) subject with the mean age was 13.2 (SD 0.32) years. Of 38 obese, there were 3 (7.9%) subject had insulin resistance. None of normoweight subjects had insulin resistance. There was a significant correlation between BMI and insulin resistance (r = 0. 601, p< 0.001). Of 38 obese subject, C allele of UCP2 A55V and C allele of UCP3 Y210Y are a risk factors of insulin resistance (OR 2.45, 95% CI 1.97-3.04 , p< 0.0001 ; OR 2.6, 95% CI 2.10-3.24, p< 0.0001 respectively), whereas UCP3 -55c/t was not considered as risk factors of insulin resistance. Our study suggest that C allele of UCP2 A55V and C allele in UCP3 Y210Y are a risk factors of insulin resistance in Indonesian obese adolescent. Larger studies is needed to prove the role of UCPs in controlling insulin resistance.

UCP2 I/D Modulated Change in BMI During a Lifestyle Modification Intervention Study in Japanese Subjects

Polymorphisms in uncoupling protein (UCP) genes have been strongly associated with energy expenditure and obesity. This study aimed at investigating the effects of UCP gene polymorphisms (UCP1 -3826A/G, UCP2A/V, UCP2 I/D, and UCP3 -55C/T) on change in body mass index (BMI) during a lifestyle modification program in Japanese subjects. Intervention induced a significant decrease in energy intake (-8.6% ± 17.0%) and a significant increase in energy expenditure (7.7% ± 7.4%). As a result, participants experienced a significant decrease in their BMI of -1.8% ± 2.7%. In a multivariate regression analysis, only UCP2 D/I among the selected UCP gene polymorphisms was associated with a change in BMI independent of the effects of gender, age, baseline BMI, changes in energy intake, and expenditure. Further regression analysis revealed that, in contrast to the DD genotype group, the DI+II genotype group showed no significant association between weight loss and change in energy expenditure suggesting this polymorphism altered the effects of this parameter on change in BMI. The study found UCP2 D/I to be associated with change in BMI by altering the effect of change in energy expenditure on change in BMI.

Association of the UCP-1 single nucleotide polymorphism A-3826G with the dampness-phlegm pattern among Korean stroke patients

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.

Impact of UCP1 and β3AR gene polymorphisms on age-related changes in brown adipose tissue and adiposity in humans

Brown adipose tissue (BAT) is involved in the regulation of whole-body energy expenditure and adiposity. The activity and prevalence of BAT decrease with age in humans. To examine the effects of single nucleotide polymorphisms of the genes for uncoupling protein 1 (UCP1) and β3-adrenergic receptor (β3AR), key molecules of BAT thermogenesis, on age-related decline of BAT activity and accumulation of body fat in humans. One hundred ninety-nine healthy volunteers (20-72 years old (y.o.)) underwent fluorodeoxyglucose-positron emission tomography (FDG-PET) and computed tomography (CT) after 2-h cold exposure to assess BAT activity. The visceral and subcutaneous fat areas at the abdominal level were estimated from the CT images. They were genotyped for -3826 A/G polymorphism of the UCP1 gene and 64 Trp/Arg mutation of the β3AR gene. BAT was detected in 88 subjects out of 199 (44%), more in younger (30 y.o., 55%) than older subjects (>40 y.o., 15%). BAT prevalence of older subjects tended to be lower in the UCP1 G/G group than the A allele group (A/A and A/G), and also in the β3AR Arg allele group (Trp/Arg and Arg/Arg) than the Trp/Trp group. When compared subjects who had two or more base substitutions on the two genes (the 2-4 allele group) with those who had less than two base substitutions (the 0-1 allele group), BAT prevalence was comparable in younger subjects (62% vs 50%) but lower in older subjects (0% vs 24%, P<0.05). Visceral fat area of the 2-4 allele group was higher than that of the 0-1 allele group (P<0.05) in older subjects, but not in younger subjects. UCP1 -3826 A/G and β3AR 64 Trp/Arg substitutions accelerate age-related decrease in BAT activity, and thereby may associate with visceral fat accumulation with age.