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Additive effect of polymorphisms in the IL-6, LTA, and TNF-{alpha} genes and plasma fatty acid level modulate risk for the metabolic syndrome and its components.
Phillips CM, Goumidi L, Bertrais S, Ferguson JF, Field MR, Kelly ED, Mehegan J, Peloso GM, Cupples LA, Shen J, Ordovas JM, McManus R, Hercberg S, Portugal H, Lairon D, Planells R, Roche HM
(2010) J Clin Endocrinol Metab 95: 1386-94
MeSH Terms: Alleles, C-Reactive Protein, Case-Control Studies, Dietary Fats, Fatty Acids, Genetic Predisposition to Disease, Genotype, Humans, Insulin, Interleukin-6, Lymphotoxin-alpha, Metabolic Syndrome, Polymorphism, Genetic, Prospective Studies, Regression Analysis, Risk Factors, Tumor Necrosis Factor-alpha, Waist Circumference
Show Abstract · Added January 20, 2015
CONTEXT - Cytokine polymorphisms and dietary fat composition may influence the risk of the metabolic syndrome (MetS).
OBJECTIVE - The objective of the study was to determine the relationship between lymphotoxin-alpha (LTA), TNF-alpha, and IL-6 gene polymorphisms with MetS risk and investigate whether plasma fatty acid composition, a biomarker of dietary fat intake, modulated these associations.
DESIGN - Polymorphisms (LTA rs915654, TNF-alpha rs1800629, IL-6 rs1800797), biochemical measurements, and plasma fatty acids were determined in the LIPGENE-SU.VI.MAX study of MetS cases and matched controls (n = 1754).
RESULTS - LTA rs915654 minor A allele carriers and TNF-alpha rs1800629 major G allele homozygotes had increased MetS risk [odds ratio (OR) 1.37 (confidence interval [CI] 1.12-1.66), P = 0.002 and OR 1.35 (CI 1.08-1.70), P = 0.009] compared with their TT homozygotes and A allele carriers. Possession of the IL-6 rs1800797 GG genotype by the LTA and TNF-alpha risk genotype carriers further increased risk of the MetS [OR 2.10 (CI 1.19-3.71) P = 0.009], fasting hyperglycemia [OR 2.65 (CI 1.12-6.28), P = 0.027], high systolic blood pressure [OR 1.99 (CI 1.07-3.72), P = 0.03], and abdominal obesity [OR 1.52 (CI 1.01-2.28), P = 0.04]. Plasma polyunsaturated to saturated fat ratio exacerbated these effects; subjects in the lowest 50th percentile had even greater risk of the MetS [OR 4.40 (CI 1.55-12.45), P = 0.005], fasting hyperglycemia, high systolic blood pressure, and abdominal obesity (P < 0.05).
CONCLUSIONS - LTA, TNF-alpha, and IL-6 genotype interactions increased MetS risk, which was further exacerbated by a low plasma polyunsaturated to saturated fat exposure, indicating important modulation of genetic risk by dietary fat exposure.
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18 MeSH Terms
Gene-nutrient interactions in the metabolic syndrome: single nucleotide polymorphisms in ADIPOQ and ADIPOR1 interact with plasma saturated fatty acids to modulate insulin resistance.
Ferguson JF, Phillips CM, Tierney AC, Pérez-Martínez P, Defoort C, Helal O, Lairon D, Planells R, Shaw DI, Lovegrove JA, Gjelstad IM, Drevon CA, Blaak EE, Saris WH, Leszczynska-Golabek I, Kiec-Wilk B, Risérus U, Karlström B, Miranda JL, Roche HM
(2010) Am J Clin Nutr 91: 794-801
MeSH Terms: Adiponectin, Adult, Aged, Alleles, Case-Control Studies, Cross-Sectional Studies, Dietary Fats, Disease Progression, Fatty Acids, Fatty Acids, Nonesterified, Female, Homozygote, Humans, Insulin Resistance, Male, Metabolic Syndrome, Middle Aged, Polymorphism, Single Nucleotide, Receptors, Adiponectin, Triglycerides, Waist Circumference
Show Abstract · Added January 20, 2015
BACKGROUND - Progression of the metabolic syndrome (MetS) is determined by genetic and environmental factors. Gene-environment interactions may be important in modulating the susceptibility to the development of MetS traits.
OBJECTIVE - Gene-nutrient interactions were examined in MetS subjects to determine interactions between single nucleotide polymorphisms (SNPs) in the adiponectin gene (ADIPOQ) and its receptors (ADIPOR1 and ADIPOR2) and plasma fatty acid composition and their effects on MetS characteristics.
DESIGN - Plasma fatty acid composition, insulin sensitivity, plasma adiponectin and lipid concentrations, and ADIPOQ, ADIPOR1, and ADIPOR2 SNP genotypes were determined in a cross-sectional analysis of 451 subjects with the MetS who participated in the LIPGENE (Diet, Genomics, and the Metabolic Syndrome: an Integrated Nutrition, Agro-food, Social, and Economic Analysis) dietary intervention study and were repeated in 1754 subjects from the LIPGENE-SU.VI.MAX (SUpplementation en VItamines et Minéraux AntioXydants) case-control study (http://www.ucd.ie/lipgene).
RESULTS - Single SNP effects were detected in the cohort. Triacylglycerols, nonesterified fatty acids, and waist circumference were significantly different between genotypes for 2 SNPs (rs266729 in ADIPOQ and rs10920533 in ADIPOR1). Minor allele homozygotes for both of these SNPs were identified as having degrees of insulin resistance, as measured by the homeostasis model assessment of insulin resistance, that were highly responsive to differences in plasma saturated fatty acids (SFAs). The SFA-dependent association between ADIPOR1 rs10920533 and insulin resistance was replicated in cases with MetS from a separate independent study, which was an association not present in controls.
CONCLUSIONS - A reduction in plasma SFAs could be expected to lower insulin resistance in MetS subjects who are minor allele carriers of rs266729 in ADIPOQ and rs10920533 in ADIPOR1. Personalized dietary advice to decrease SFA consumption in these individuals may be recommended as a possible therapeutic measure to improve insulin sensitivity. This trial was registered at clinicaltrials.gov as NCT00429195.
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21 MeSH Terms
The association of pericardial fat with incident coronary heart disease: the Multi-Ethnic Study of Atherosclerosis (MESA).
Ding J, Hsu FC, Harris TB, Liu Y, Kritchevsky SB, Szklo M, Ouyang P, Espeland MA, Lohman KK, Criqui MH, Allison M, Bluemke DA, Carr JJ
(2009) Am J Clin Nutr 90: 499-504
MeSH Terms: Adipose Tissue, Aged, Aged, 80 and over, Atherosclerosis, Body Mass Index, Case-Control Studies, Cohort Studies, Coronary Disease, Female, Humans, Incidence, Male, Middle Aged, Pericardium, Risk Factors, Tomography, X-Ray Computed, Waist Circumference
Show Abstract · Added February 28, 2014
BACKGROUND - Pericardial fat (ie, fat around the heart) may have a direct role in the atherosclerotic process in coronary arteries through local release of inflammation-related cytokines. Cross-sectional studies suggest that pericardial fat is positively associated with coronary artery disease independent of total body fat.
OBJECTIVE - We investigated whether pericardial fat predicts future coronary heart disease events.
DESIGN - We conducted a case-cohort study in 998 individuals, who were randomly selected from 6814 Multi-Ethnic Study of Atherosclerosis (MESA) participants and 147 MESA participants (26 from those 998 individuals) who developed incident coronary heart disease from 2000 to 2005. The volume of pericardial fat was determined from cardiac computed tomography at baseline.
RESULTS - The age range of the subjects was 45-84 y (42% men, 45% white, 10% Asian American, 22% African American, and 23% Hispanic). Pericardial fat was positively correlated with both body mass index (correlation coefficient = 0.45, P < 0.0001) and waist circumference (correlation coefficient = 0.57, P < 0.0001). In unadjusted analyses, pericardial fat (relative hazard per 1-SD increment: 1.33; 95% CI: 1.15, 1.54), but not body mass index (1.00; 0.84, 1.18), was associated with the risk of coronary heart disease. Waist circumference (1.14; 0.97, 1.34; P = 0.1) was marginally associated with the risk of coronary heart disease. The relation between pericardial fat and coronary heart disease remained significant after further adjustment for body mass index and other cardiovascular disease risk factors (1.26; 1.01, 1.59). The relation did not differ by sex.
CONCLUSION - Pericardial fat predicts incident coronary heart disease independent of conventional risk factors, including body mass index.
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17 MeSH Terms
General and abdominal adiposity and risk of stroke in Chinese women.
Zhang X, Shu XO, Gao YT, Yang G, Li H, Zheng W
(2009) Stroke 40: 1098-104
MeSH Terms: Abdominal Fat, Adult, Aged, Asian Continental Ancestry Group, Body Mass Index, China, Female, Follow-Up Studies, Humans, Middle Aged, Multivariate Analysis, Obesity, Prospective Studies, Risk Factors, Stroke, Waist Circumference, Waist-Hip Ratio
Show Abstract · Added March 7, 2014
BACKGROUND AND PURPOSE - Although both general and abdominal adiposity are well-established risk factors for coronary heart disease, their associations with stroke are less well characterized, particularly in generally lean Asian populations.
METHODS - We evaluated associations of body mass index (BMI), waist-hip ratio (WHR), waist circumference (WC), and waist-height ratio (WHtR) with stroke risk in the Shanghai Women's Health Study, a population-based prospective cohort study of 74 942 Chinese women aged 40 to 70 years with anthropometric measurement taken at recruitment in 1996 to 2000. For this analysis, we included 67 083 women with no prior history of stroke, coronary heart disease, rheumatic heart disease, cardiac surgery, or cancer at recruitment. Incident stroke was ascertained by biennial home visits and linkage with vital statistics registries.
RESULTS - Cut points for the highest quintiles of BMI, WHR, WC, and WHtR among this cohort were 26.6 (kg/m(2)), 0.85 (cm/cm), 84.1 (cm), and 0.54 (cm/cm), respectively. During a mean follow-up of 7.3 years, 2403 incident stroke cases were identified. All selected anthropometric measurements were positively and significantly associated with risk of total, ischemic, and hemorrhagic stroke in a dose-response manner (all probability values for trend <0.01). The multivariable-adjusted hazard ratios (95% confidence intervals) for total stroke comparing the highest versus lowest quintiles of these measurements were 1.71 (1.49 to 1.97), 1.59 (1.37 to 1.85), 1.77 (1.53 to 2.05), and 1.91 (1.61 to 2.27) for BMI, WHR, WC, and WHtR, respectively.
CONCLUSIONS - Increasing levels of general or abdominal adiposity consistently predict increased risk of stroke in predominantly nonobese Chinese women.
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17 MeSH Terms