RESUMEN
OBJECTIVE: Waist circumference (WC), the clinical marker of central obesity, is gaining popularity as a screening tool for type 2 diabetes (T2D). While there is epidemiologic evidence favoring the WC-T2D association, its biological substantiation is generally weak. Our objective was to determine the independent association of plasma lipid repertoire with WC. METHODS: Samples and data from the San Antonio Family Heart Study of 1208 Mexican Americans from 42 extended families were used. Association of plasma lipidomic profiles with the cross-sectionally assessed WC was determined. Plasma lipidomic profiling entailed liquid chromatography with mass spectrometry. Statistical analyses included multivariable polygenic regression models and bivariate trait analyses using the SOLAR software. RESULTS: After adjusting for age and sex interactions, body mass index, homeostasis model of assessment-insulin resistance, total cholesterol, triglycerides, high density lipoproteins and use of lipid lowering drugs, dihydroceramides as a class were associated with WC. Dihydroceramide species 18:0, 20:0, 22:0, and 24:1 were significantly associated and genetically correlated with WC. Two sphingomyelin species (31:1 and 41:1) were also associated with WC. CONCLUSIONS: Plasma dihydroceramide levels independently associate with WC. Thus, high resolution plasma lipidomic studies can provide further credence to the biological underpinnings of the association of WC with T2D.
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Ceramidas/sangre , Diabetes Mellitus Tipo 2/etnología , Americanos Mexicanos , Obesidad/etnología , Circunferencia de la Cintura , Adulto , Glucemia , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/etnología , Colesterol/sangre , Estudios Transversales , Diabetes Mellitus Tipo 2/sangre , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Obesidad/sangre , Prevalencia , Encuestas y Cuestionarios , Texas/epidemiología , Triglicéridos/sangre , Adulto JovenRESUMEN
Both as a component of metabolic syndrome and as an independent entity, hypertension poses a continued challenge with regard to its diagnosis, pathogenesis, and treatment. Previous studies have documented connections between hypertension and indicators of lipid metabolism. Novel technologies, such as plasma lipidomic profiling, promise a better understanding of disorders in which there is a derangement of the lipid metabolism. However, association of plasma lipidomic profiles with hypertension in a high-risk population, such as Mexican Americans, has not been evaluated before. Using the rich data and sample resource from the ongoing San Antonio Family Heart Study, we conducted plasma lipidomic profiling by combining high-performance liquid chromatography with tandem mass spectroscopy to characterize 319 lipid species in 1192 individuals from 42 large and extended Mexican American families. Robust statistical analyses using polygenic regression models, liability threshold models, and bivariate trait analyses implemented in the SOLAR software were conducted after accounting for obesity, insulin resistance, and relative abundance of various lipoprotein fractions. Diacylglycerols, in general, and the DG 16:0/22:5 and DG 16:0/22:6 lipid species, in particular, were significantly associated with systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP), as well as liability of incident hypertension measured during 7140.17 person-years of follow-up. Four lipid species, including the DG 16:0/22:5 and DG 16:0/22:6 species, showed significant genetic correlations with the liability of hypertension in bivariate trait analyses. Our results demonstrate the value of plasma lipidomic profiling in the context of hypertension and identify disturbance of diacylglycerol metabolism as an independent biomarker of hypertension.
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Diglicéridos/sangre , Hipertensión/sangre , Metabolismo de los Lípidos/fisiología , Lípidos/sangre , Americanos Mexicanos , Adulto , Anciano , Cromatografía Líquida de Alta Presión , Estudios Transversales , Femenino , Humanos , Hipertensión/etnología , Resistencia a la Insulina/etnología , Resistencia a la Insulina/fisiología , Masculino , Persona de Mediana Edad , Espectrometría de Masas en TándemRESUMEN
Plasma lipidomic studies using high performance liquid chromatography and mass spectroscopy offer detailed insights into metabolic processes. Taking the example of the most abundant plasma lipid class (phosphatidylcholines) we used the rich phenotypic and lipidomic data from the ongoing San Antonio Family Heart Study of large extended Mexican-American families to assess the variability of association of the plasma phosphatidylcholine species with metabolic syndrome. Using robust statistical analytical methods, our study made two important observations. First, there was a wide variability in the association of phosphatidylcholine species with risk measures of metabolic syndrome. Phosphatidylcholine 40:7 was associated with a low risk while phosphatidylcholines 32:1 and 38:3 were associated with a high risk of metabolic syndrome. Second, all the odd chain phosphatidylcholines were associated with a reduced risk of metabolic syndrome implying that phosphatidylcholines derived from dairy products might be beneficial against metabolic syndrome. Our results demonstrate the value of lipid species-specific information provided by the upcoming array of lipidomic studies and open potential avenues for prevention and control of metabolic syndrome in high prevalence settings.
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Síndrome Metabólico/sangre , Fosfatidilcolinas/sangre , Adulto , Cromatografía Líquida de Alta Presión , Femenino , Humanos , Masculino , Espectrometría de Masas , Síndrome Metabólico/epidemiología , Americanos Mexicanos , Persona de Mediana Edad , Fosfatidilcolinas/análisis , Factores de Riesgo , Estados Unidos/epidemiologíaRESUMEN
CONTEXT: Chemerin is a novel adipokine previously associated with metabolic syndrome phenotypes in a small sample of subjects from Mauritius. OBJECTIVE: The aim of the study was to determine whether plasma chemerin levels were associated with metabolic syndrome phenotypes in a larger sample from a second, unrelated human population. DESIGN, SETTING, PATIENTS, AND INTERVENTION: Plasma samples were obtained from the San Antonio Family Heart Study (SAFHS), a large family-based genetic epidemiological study including 1431 Mexican-American individuals. Individuals were randomly sampled without regard to phenotype or disease status. This sample is well-characterized for a variety of phenotypes related to the metabolic syndrome. MAIN OUTCOMES: Plasma chemerin levels were measured by sandwich ELISA. Linear regression and correlation analyses were used to determine associations between plasma chemerin levels and metabolic syndrome phenotypes. RESULTS: Circulating chemerin levels were significantly higher in nondiabetic subjects with body mass index (BMI) greater than 30 kg/m(2) compared with those with a BMI below 25 kg/m(2) (P < 0.0001). Plasma chemerin levels were significantly associated with metabolic syndrome-related parameters, including BMI (P < 0.0001), fasting serum insulin (P < 0.0001), triglycerides (P < 0.0001), and high-density lipoprotein cholesterol (P = 0.00014), independent of age and sex in nondiabetic subjects. CONCLUSION: Circulating chemerin levels were associated with metabolic syndrome phenotypes in a second, unrelated human population. This replicated result using a large human sample suggests that chemerin may be involved in the development of the metabolic syndrome.
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Quimiocinas/sangre , Síndrome Metabólico/sangre , Síndrome Metabólico/etnología , Americanos Mexicanos , Adulto , Anciano , Quimiocinas/fisiología , Diabetes Mellitus Tipo 2/sangre , Femenino , Humanos , Péptidos y Proteínas de Señalización Intercelular , Masculino , Persona de Mediana Edad , Obesidad/sangre , Sobrepeso/sangre , FenotipoRESUMEN
BACKGROUND: Elevated serum uric acid is associated with several cardiovascular disease (CVD) risk factors such as hypertension, inflammation, endothelial dysfunction, insulin resistance, dyslipidemia, and obesity. However, the role of uric acid as an independent risk factor for CVD is not yet clear. OBJECTIVE: The aim of the study was to localize quantitative trait loci regulating variation in serum uric acid and also establish the relationship between serum uric acid and other CVD risk factors in Mexican Americans (n = 848; men = 310, women = 538) participating in the San Antonio Family Heart Study. METHODS: Quantitative genetic analysis was conducted using variance components decomposition method, implemented in the software program SOLAR. RESULTS: Mean +/- SD of serum uric acid was 5.35 +/- 1.38 mg/dl. Univariate genetic analysis showed serum uric acid and other CVD risk markers to be significantly heritable (P < 0.005). Bivariate analysis showed significant correlation of serum uric acid with body mass index, waist circumference, waist/hip ratio, total body fat, plasma insulin, serum triglycerides, high-density lipoprotein cholesterol, C-reactive protein, and granulocyte macrophage-colony stimulating factor (P < 0.05). A genome-wide scan for detecting quantitative trait loci regulating serum uric acid variation showed a significant logarithm of odds (LOD) score of 4.72 (empirical LOD score = 4.62; P < 0.00001) on chromosome 3p26. One LOD support interval contains 25 genes, of which an interesting candidate gene is chemokine receptor 2. SUMMARY: There is a significant genetic component in the variation in serum uric acid and evidence of pleiotropy between serum uric acid and other cardiovascular risk factors.
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Enfermedades Cardiovasculares/genética , Variación Genética , Americanos Mexicanos/genética , Ácido Úrico/sangre , Adulto , Enfermedades Cardiovasculares/sangre , Cromosomas Humanos Par 3 , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Escala de Lod , Masculino , Persona de Mediana Edad , Sitios de Carácter Cuantitativo , Factores de RiesgoRESUMEN
Although previous genome scans have searched for quantitative-trait loci (QTLs) influencing variation in blood pressure (BP), few have investigated the rate of change in BP over time as a phenotype. Here, we compare results from genomewide scans to localize QTLs for systolic, diastolic, and mean arterial BPs (SBP, DBP, and MBP, respectively) and for rates of change in systolic, diastolic, and mean arterial BPs (rSBP, rDBP, and rMBP, respectively), with use of the longitudinal data collected about Mexican Americans of the San Antonio Family Heart Study (SAFHS). Significant evidence of linkage was found for rSBP (LOD 4.15) and for rMBP (LOD 3.94) near marker D11S4464 located on chromosome 11q24.1. This same chromosome 11q region also shows suggestive linkage to SBP (LOD 2.23) and MBP (LOD 2.37) measurements collected during the second clinic visit. Suggestive evidence of linkage to chromosome 5 was also found for rMBP, to chromosome 16 for rSBP, and to chromosomes 1, 5, 6, 7, and 21 for the single-time-point BP traits collected at the first two SAFHS clinic visits. We also present results from fine mapping the chromosome 11 QTL with use of SNP-association analysis within candidate genes identified from a bioinformatic search of the region and from whole-genome transcriptional expression data collected from 1,240 SAFHS participants. Our results show that the use of longitudinal BP data to calculate the rate of change in BP over time provides more information than do the single-time measurements, since they reveal physiological trends in the subjects that a single-time measurement could never capture. Further investigation of this region is necessary for the identification of the genetic variation responsible for QTLs influencing the rate of change in BP.