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Association between the FTO rs9939609 polymorphism and the metabolic syndrome in a non-Caucasian multi-ethnic sample
Salam A Al-Attar, Rebecca L Pollex, Matthew R Ban, T Kue Young, Peter Bjerregaard, Sonia S Anand, Salim Yusuf, Bernard Zinman, Stewart B Harris, Anthony JG Hanley, Philip W Connelly, Murray W Huff, Robert A Hegele
Cardiovascular Diabetology , 2008, DOI: 10.1186/1475-2840-7-5
Abstract: The FTO rs9939609 SNP was genotyped in 2121 subjects from four different non-Caucasian geographical ancestries. Subjects were classified for the presence or absence of MetS according to the International Diabetes Federation (IDF) and National Cholesterol Education Program Adult Treatment Panel (NCEP ATP) III definitions.Carriers of ≥ 1 copy of the rs9939609 A allele were significantly more likely to have IDF-defined MetS (35.8%) than non-carriers (31.2%), corresponding to a carrier odds ratio (OR) of 1.23 (95% confidence interval [CI] 1.01 to 1.50), with a similar trend for the NCEP ATP III-defined MetS. Subgroup analysis showed that the association was particularly strong in men. The association was related to a higher proportion of rs9939609 A allele carriers meeting the waist circumference criterion; a higher proportion also met the HDL cholesterol criterion compared with wild-type homozygotes.Thus, the FTO rs9939609 SNP was associated with an increased risk for MetS in this multi-ethnic sample, confirming that the association extends to non-Caucasian population samples.The metabolic syndrome (MetS) is a clinical entity characterized by abdominal obesity, hypertension, hypertriglyceridemia, depressed plasma high-density lipoprotein (HDL) cholesterol and elevated glucose [1,2]. MetS is common, and will likely become even more pervasive, considering the poor lifestyle habits prevalent in many societies today. While the increased prevalence of MetS is primarily related to an imbalance between caloric intake and expenditure, genetic factors are also likely to be important. Each defining component has been previously associated with genetic factors, suggesting that genetic factors might underlie the overall MetS both independently and through more complex interactions [3]. While the precise definition of MetS is controversial, there is no question that the MetS concept has proven to be valuable clinically [4,5].A potential candidate underlying genetic susceptibility t
Association between the -455T>C promoter polymorphism of the APOC3 gene and the metabolic syndrome in a multi-ethnic sample
Rebecca L Pollex, Matthew R Ban, T Kue Young, Peter Bjerregaard, Sonia S Anand, Salim Yusuf, Bernard Zinman, Stewart B Harris, Anthony JG Hanley, Philip W Connelly, Murray W Huff, Robert A Hegele
BMC Medical Genetics , 2007, DOI: 10.1186/1471-2350-8-80
Abstract: Subjects were genotyped for both the APOC3 -455T>C and INSIG2 rs7566605 polymorphisms, and classified for the presence or absence of MetS (NCEP ATP III and IDF definitions). The total study population included 2675 subjects (≥18 years of age) from six different geographical ancestries.For the overall study population, the prevalence of MetS was 22.6% (NCEP ATP III definition). Carriers of ≥1 copy of APOC3 -455C were more likely to have MetS (NCEP ATP III definition) than noncarriers (carrier odds ratio 1.73, 95% CI 1.40 to 2.14, adjusting for age and study group). The basis of the association was related not only to a higher proportion of -455C carriers meeting the triglyceride and high-density lipoprotein cholesterol criteria, but also the blood pressure criteria compared with wild-type homozygotes. Plasma apo C-III concentrations were not associated with APOC3 -455T>C genotype. The INSIG2 rs7566605 polymorphism was not associated with MetS or measures of obesity.Meta-analysis of the sample of multiple geographic ancestries indicated that the functional -455T>C promoter polymorphism in APOC3 was associated with an approximately 2-fold increased risk of MetS, whereas the INSIG2 rs7566605 polymorphism was not associated with MetS.The metabolic syndrome (MetS) is a clinical entity characterized by abdominal obesity, hypertension, hypertriglyceridemia, low plasma high-density lipoprotein (HDL) cholesterol and elevated glucose [1,2]. MetS is common, and will likely become even more pervasive, considering the poor lifestyle habits prevalent in many societies today. While the increased prevalence in MetS is primarily related to an imbalance between caloric intake and expenditure, genetic factors are also likely to be important. Each defining component has been previously associated with genetic factors, suggesting that genetic factors might underlie the overall MetS both independently and through more complex interactions [3]. While the precise definition of MetS is contr
Ethnic Differences in the Prevalence of Metabolic Syndrome: Results from a Multi-Ethnic Population-Based Survey in Malaysia  [PDF]
Sanjay Rampal, Sanjiv Mahadeva, Eliseo Guallar, Awang Bulgiba, Rosmawati Mohamed, Ramlee Rahmat, Mohamad Taha Arif, Lekhraj Rampal
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0046365
Abstract: Introduction The prevalence of metabolic syndrome is increasing disproportionately among the different ethnicities in Asia compared to the rest of the world. This study aims to determine the differences in the prevalence of metabolic syndrome across ethnicities in Malaysia, a multi-ethnic country. Methods In 2004, we conducted a national cross-sectional population-based study using a stratified two-stage cluster sampling design (N = 17,211). Metabolic syndrome was defined according to the International Diabetes Federation/National Heart, Lung and Blood Institute/American Heart Association (IDF/NHLBI/AHA-2009) criteria. Multivariate models were used to study the independent association between ethnicity and the prevalence of the metabolic syndrome. Results The overall mean age was 36.9 years, and 50.0% participants were female. The ethnic distribution was 57.0% Malay, 28.5% Chinese, 8.9% Indian and 5.0% Indigenous Sarawakians. The overall prevalence of the metabolic syndrome was 27.5%, with a prevalence of central obesity, raised triglycerides, low high density lipoprotein cholesterol, raised blood pressure and raised fasting glucose of 36.9%, 29.3%, 37.2%, 38.0% and 29.1%, respectively. Among those <40 years, the adjusted prevalence ratios for metabolic syndrome for ethnic Chinese, Indians, and Indigenous Sarawakians compared to ethnic Malay were 0.81 (95% CI 0.67 to 0.96), 1.42 (95% CI 1.19 to 1.69) and 1.37 (95% CI 1.08 to 1.73), respectively. Among those aged ≥40 years, the corresponding prevalence ratios were 0.86 (95% CI 0.79 to 0.92), 1.25 (95% CI 1.15 to 1.36), and 0.94 (95% CI 0.80, 1.11). The P-value for the interaction of ethnicity by age was 0.001. Conclusions The overall prevalence of metabolic syndrome in Malaysia was high, with marked differences across ethnicities. Ethnic Chinese had the lowest prevalence of metabolic syndrome, while ethnic Indians had the highest. Indigenous Sarawakians showed a marked increase in metabolic syndrome at young ages.
Adiponectin and Leptin Metabolic Biomarkers in Chinese Children and Adolescents  [PDF]
Jie Mi,Mercedes Nancy Munkonda,Ming Li,Mei-Xian Zhang,Xiao-Yuan Zhao,Ponce Cedric Wamba Fouejeu,Katherine Cianflone
Journal of Obesity , 2010, DOI: 10.1155/2010/892081
Abstract: Objective. To evaluate leptin and adiponectin as biomarkers of metabolic syndrome (MS) risk factors even in nonobese children/adolescents. Methods. Serum leptin, adiponectin, leptin:adiponectin ratio, lipids, glucose, and insulin concentrations as well as body size parameters and pubertal development were evaluated in a large population of Chinese children/adolescents ( , 6–18 years, 1722 girls and 1783 boys). Results. Leptin concentration increased while adiponectin decreased with obesity, both were influenced by pubertal development. Central obesity had an additive effect on leptin levels (above obesity alone). Leptin/adiponectin increased 8.4-fold and 3.2-fold in overweight/obesity, and 15.8- and 4.5-fold with obesity plus MS, in early and late puberty, respectively. Even in normal weight children/adolescents, higher leptin and lower adiponectin concentrations associated with increased risk profile. Conversely, overweight/obese with lower leptin or higher adiponectin concentrations had a less compromised metabolic profile. Conclusion. Leptin, adiponectin, and leptin:adiponectin ratio are informative biomarkers for obesity, central obesity, MS, and abnormal metabolic profile even in normal weight children/adolescents. 1. Introduction The alarming increase in obesity worldwide is of concern, due to the associations of obesity with metabolic syndrome (MS), insulin resistance, Type 2 diabetes, dyslipidaemia and cardiovascular disease [1, 2]. This increase is noted even in populations previously at reduced risk, such as Asia [3], even in children [4]. MS is characterized by central obesity, insulin resistance, hyperglycaemia, dyslipidaemia (increased triglyceride and decreased HDL), and hypertension; all risk factors for cardiovascular disease and Type 2 diabetes mellitus. Characterization of MS potentially identifies individuals predisposed to cardiovascular disease and Type 2 diabetes, allowing measures to be instituted early-on [3]. Adult urban versus rural populations are at higher MS risk [5] and prevalence varies with gender, age, ethnic background, and residence [1, 5]. Puberty, with naturally occurring growth spurts and hormonal changes coupled to behavioural changes, is a critical period for development of obesity and childhood MS [6]. Further, the associated pathological processes and risk factors have been observed in obese children and adolescents [7–9]. Adipose tissue secretes adipokines influencing body weight, glucose, and lipid metabolism [7]. Adiponectin, a collagen-like protein exclusively expressed in adipose tissue, has
A confirmatory factor analysis of the metabolic syndrome in adolescents: an examination of sex and racial/ethnic differences
Matthew J Gurka, Christa L Ice, Shumei S Sun, Mark D DeBoer
Cardiovascular Diabetology , 2012, DOI: 10.1186/1475-2840-11-128
Abstract: Using 1999–2010 data from the National Health and Nutrition Examination Survey (NHANES), we performed a confirmatory factor analysis of a single MetS factor that allowed differential loadings across sex and race/ethnicity, resulting in a continuous MetS risk score that is sex and race/ethnicity-specific.Loadings to the MetS score differed by racial/ethnic and gender subgroup with respect to triglycerides and HDL-cholesterol. ROC-curve analysis revealed high area-under-the-curve concordance with MetS by traditional criteria (0.96), and with elevations in MetS-associated risk markers, including high-sensitivity C-reactive protein (0.71), uric acid (0.75) and fasting insulin (0.82). Using a cut off for this score derived from ROC-curve analysis, the MetS risk score exhibited increased sensitivity for predicting elevations in ≥2 of these risk markers as compared with traditional pediatric MetS criteria.The equations from this sex- and race/ethnicity-specific analysis provide a clinically-accessible and interpretable continuous measure of MetS that can be used to identify children at higher risk for developing adult diseases related to MetS, who could then be targeted for intervention. These equations also provide a powerful new outcome for use in childhood obesity and MetS research.The metabolic syndrome (MetS) is a cluster of interrelated individual factors that increase risk for future Type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) [1,2]. These individual components of MetS include elevations in adiposity, triglycerides, blood pressure (BP) and fasting glucose, and low levels of high-density lipoprotein (HDL) particles (a surrogate for which is HDL cholesterol) [3]. While the pathophysiologic processes that drive abnormalities in these individual components are not fully understood, these underlying processes appear to be related to systemic insulin resistance [3]. In an attempt to understand the existence of MetS and the contributions of clinical me
Plasma fatty acids and the risk of metabolic syndrome in ethnic Chinese adults in Taiwan
Kuo-Liong Chien, Chia-Lun Chao, Chen-Hong Kuo, Hung-Ju Lin, Pi-Hua Liu, Pei-Rony Chen, Hsiu-Ching Hsu, Bai-Chin Lee, Yuan-Teh Lee, Ming-Fong Chen
Lipids in Health and Disease , 2011, DOI: 10.1186/1476-511x-10-33
Abstract: A nested case-control study based on 1000 cases of metabolic syndrome and 1:1 matched control subjects. For saturated fat, monounsaturated fat and transfat, the higher the concentration the higher the risk for metabolic syndrome: participants in the highest quintile had a 2.22-fold (95% confidence interval [CI], 1.66 to 2.97) higher risk of metabolic syndrome. In addition, the participants in higher EPA quintiles were less likely to have the risk of metabolic syndrome (adjusted risk, 0.46 [0.34 to 0.61] for the fifth quintile). Participants in the highest risk group (low EPA and high transfat) had a 2.36-fold higher risk of metabolic syndrome (95% CI, 1.38 to 4.03), compared with those in the lowest risk group (high EPA and low transfat). For prediction power, the area under ROC curves increased from 0.926 in the baseline model to 0.928 after adding fatty acids. The net reclassification improvement for metabolic syndrome risk was substantial for saturated fat (2.1%, P = 0.05).Plasma fatty acid components improved the prediction of the metabolic syndrome risk in Taiwan.Identifying dietary factors for the development of type 2 diabetes and metabolic syndrome is essential for primary prevention [1,2]. Dietary intake habits of fatty acids, including consumption of foods with high saturated fat and high transfat contents, are associated with insulin resistance and hyperlipidemia [3]. In addition, transfat has frequently been reported to be risk factors for cardiovascular diseases [4,5], and the evidence for monounsaturated fats was inconclusive[6]. In contrast, marine-derived fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are inversely related to type 2 diabetes due to reduced inflammation and increased insulin sensitivity [7]. However, although there have been many studies about the association of specific fatty acids and the risk of cardiovascular diseases, there have only been a limited number of integrated comparison studies. Previous
Lack of Association of the Ghrelin Gene Arg51Gln Single Nucleotide Polymorphism with Obesity and Metabolic Syndrome among Multi-ethnic Malaysian Subjects
International Journal of Diabetes Research , 2012, DOI: 10.5923/j.diabetes.20120103.03
Abstract: Obesity and metabolic syndrome has become a public health concern because of its association with a number of medical complications that lead to increased morbidity and mortality. Ghrelin is a hormone that is primarily secreted in the stomach, which plays an important role to increase hunger through its action on hypothalamic feeding. The Ghrelin gene Arg51Gln single nucleotide polymorphism (SNP) (rs34911341) has been associated with obesity and metabolic syndrome in previous studies. Therefore, this study was to examine the prevalence of this SNP and its association with obesity, obesity-related traits and metabolic syndrome among 184 multi-ethnic Malaysian subjects (67 males, 117 females; 76 obese, 108 non obese; 52 Malay, 91 ethnic Chinese, 41 ethnic Indians) from the Kampar Health Clinic cohort. Demographic data, anthropometric and clinical measurements of subjects were collected. Genotyping was performed by using the genomic DNA extracted from leukocytes, followed by Polymerase Chain Reaction and SacI Restriction Fragment Length Polymorphism, revealing 113 GG, 70 GA and 1 AA subjects; minor allele frequency 0.196. Arg51Gln alleles did not show any association with obesity (p = 0.643), gender (p = 0.064) and ethnicity (p = 0.390). Besides, it did not show any association with the presence of metabolic syndrome according to 3 criteria in the modified NCEP ATP III for Asians (p = 0.931). Anthropometric and clinical measurements indicative of obesity and metabolic syndrome were also all not significantly different between the alleles. In conclusion, the Ghrelin Arg51Gln gene variant was not associated with obesity, obesity-related traits and metabolic syndrome among Malaysian subjects in this study.
Is impaired energy regulation the core of the metabolic syndrome in various ethnic groups of the USA and Taiwan?
Mark L Wahlqvist, Hsing-Yi Chang, Chu-Chih Chen, Chih-Cheng Hsu, Wan-Chi Chang, Wuan-Szu Wang, Chao A Hsiung
BMC Endocrine Disorders , 2010, DOI: 10.1186/1472-6823-10-11
Abstract: National Health and Nutrition Examination Survey (NHANES 2001-2) with n = 2254 and Taiwanese National Health Interview Survey (NHIS) sub-set for hypertension, hyperglycemia and hyperlipidemia assessment (TwSHHH 2002), n = 5786, were used to compare different ethnicities according to NCEP-ATPIII (NCEP-tw) criteria for METS. Exploratory factor analysis (EFA) using principal components (PC) was employed to differentiate and unify MetS components across four ethnicities, gender, age-strata, and urban-rural settings.The first two factors from the PC analysis (PCA) accounted for from 55.2% (non-Hispanic white) to 63.7% (Taiwanese) of the variance. Rotated factor loadings showed that the six MetS components provided three clusters: the impaired energy regulation (IER) components (waist circumference, WC, fasting triglycerides, TG, and fasting plasma glucose, FPG), systolic and diastolic blood pressures (BPs), and HDL-cholesterol, where the IER components accounted for 25-26% of total variance of MetS components. For the three US ethnic subgroups, factor 1 was mainly determined by IER and HDL-cholesterol, and factor 2 was related to the BP components. For Taiwanese, IER was determinant for both factors, and BPs and HDL-cholesterol were related to factors 1 and 2 respectively.There is a MetS core which unifies populations. It comprises WC, TG and FPG as a core, IER, which may be expressed and modulated in various second order ways.The metabolic syndrome (MetS) was conceptualized on the basis that a cluster of metabolic phenomena could be observed in those prone to cardiovascular disease ahead of frank diabetes. It combined features of possible pathogenesis with risk evaluation. Its definition has been in evolution, but those currently used include that of the International Diabetes Federation (IDF) in 2005 [1,2] and the joint NHLB (National Heart Lung and Blood) Institute/AHA (American Heart Association) definition of 2004 [3], based on the NCEP-ATP III (National Cholesterol
The Association of 25 Hydroxyvitamin D and Parathyroid Hormone with Metabolic Syndrome in Two Ethnic Groups in South Africa  [PDF]
Jaya A. George, Shane A. Norris, Hendrik Emmanuel van Deventer, Nigel J. Crowther
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0061282
Abstract: Introduction Though inconsistent, a number of studies have shown an association between vitamin D (25(OH)D) status, parathyroid hormone (PTH) and the metabolic syndrome (Met S). These have largely been carried out in Caucasians or black subjects living in high income countries. There no data on the relationship of 25(OH)D and PTH status with Met S in populations resident in Africa. The aims of this study were to evaluate if there was an association of 25(OH)D or PTH with Met S in non-Caucasian populations in South Africa, and whether these molecules explained ethnic differences in the prevalence of Met S and its individual components. Methods We measured anthropometry, serum 25(OH)D and PTH levels and the components of Met S, plus related metabolic variables, in 374 African and 350 Asian Indian healthy adults from the greater Johannesburg metropolitan area. Results Met S was diagnosed in 29% of the African and 46% of the Asian Indian subjects (p<0.0001). Subjects with Met S had higher PTH than those without Met S, (p<0.0001), whilst 25(OH)D levels were not significantly different (p = 0.50). In multivariate analysis, 25(OH)D was not associated with any components of the Met S however PTH was shown to be positively associated with systolic (p = 0.018) and diastolic (p = 0.005) blood pressures and waist circumference (p<0.0001) and negatively associated with HOMA (p = 0.0008) levels. Logistic regression analysis showed that Asian Indian ethnicity (OR 2.24; 95% CIs 1.57, 3.18; p<0.0001) and raised PTH (OR 2.48; 95% CIs 1.01, 6.08; p = 0.04; adjusted for 25(OH)D) produced an increased risk of Met S but 25(OH)D did not (OR 1.25; 95% CI 0.67, 2.24; p = 0.48). Conclusions Plasma PTH but not 25(OH)D is an independent predictor of the Met S in African and Asian Indians in South Africa.
Association between dietary patterns and metabolic syndrome in a sample of portuguese adults  [cached]
Fonseca Maria,Gaio Rita,Lopes Carla,Santos Ana
Nutrition Journal , 2012, DOI: 10.1186/1475-2891-11-64
Abstract: Background There is scarce evidence regarding the association between diet and metabolic syndrome (MetS) in Portuguese population. We aim to evaluate the association between a posteriori dietary patterns (DPs) and MetS and its features. Methods Using random digit dialing, a sample of 2167 adults was selected between 1999 and 2003, in Porto. During a face-to-face interview, a questionnaire was applied, anthropometric measures were taken, blood pressure measured and a fasting blood sample collected. Diet was assessed using a validated food frequency questionnaire, and four DPs were identified in each sex by multivariate finite mixture models. Results After adjustment for age and daily energy intake, comparing to the “healthy” DP, women with the “low fruit and vegetables” DP had a higher odds of high waist circumference (OR = 1.88 95% CI 1.17-3.01) and low HDL-cholesterol (OR = 1.78 95% IC 1.12-2.82) and women in the “red meat and alcohol” DP had higher odds of high waist circumference (OR = 1.45 95% CI 1.01-2.07) and of MetS (OR = 1.57 95% CI 1.07-2.29); men with the “fish” DP had a higher odds of high triglycerides (OR = 1.57 95% CI 1.05-2.35). After further adjustments (education, physical activity, smoking, alcohol drinking, BMI, and menopausal status) no significant associations remained. Conclusions Four distinct DPs were identified in a community sample of Portuguese adults and there was no association with the prevalence of MetS.
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