Meta-analysis on the G-308A tumor necrosis factor alpha gene variant and phenotypes associated with the metabolic syndrome.
ABSTRACT The G-308A tumor necrosis factor (TNF) alpha gene variant has been associated with obesity, insulin resistance, and hypertension. We performed a systematical review of the literature by means of a meta-analysis to assess the association of the G-308A TNFalpha polymorphism with the components of the metabolic syndrome.
Studies were identified by searches of the literature for reports using the terms: diabetes, insulin resistance, hypertension, obesity or metabolic syndrome and TNF, variants or polymorphism or alleles, and Nco or -308. From 824 reports, we included 31 observational studies, case control and cohort at baseline, which analyzed the association between the TNFalpha polymorphism and one or more components of the metabolic syndrome. A fixed effect model was used to pool data from individual studies.
Obesity [odds ratio, 1.23; 95% confidence interval (CI), 1.045 to 1.45; p = 0.013] in a total of 3562 individuals from eight homogeneous studies, systolic arterial blood pressure (standardized difference, 0.132; 95% CI, 0.016 to 0.25; p < 0.03) in a total of 1624 individuals from four homogeneous studies and plasma insulin levels (standardized difference, 0.095; 95% CI, 0.020 to 0.17; p = 0.013) in a total of 3720 subjects from 16 homogeneous studies were positively associated with the -308A variant.
These results indicate that individuals who carried the -308A TNFalpha gene variant are at 23% risk of developing obesity compared with controls and showed significantly higher systolic arterial blood pressure and plasma insulin levels, supporting the hypothesis that the TNFalpha gene is involved in the pathogenesis of the metabolic syndrome.
Article: Genetic variants associated with fasting blood lipids in the U.S. population: Third National Health and Nutrition Examination Survey.[show abstract] [hide abstract]
ABSTRACT: The identification of genetic variants related to blood lipid levels within a large, population-based and nationally representative study might lead to a better understanding of the genetic contribution to serum lipid levels in the major race/ethnic groups in the U.S. population. Using data from the second phase (1991-1994) of the Third National Health and Nutrition Examination Survey (NHANES III), we examined associations between 22 polymorphisms in 13 candidate genes and four serum lipids: high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TG). Univariate and multivariable linear regression and within-gene haplotype trend regression were used to test for genetic associations assuming an additive mode of inheritance for each of the three major race/ethnic groups in the United States (non-Hispanic white, non-Hispanic black, and Mexican American). Variants within APOE (rs7412, rs429358), PON1 (rs854560), ITGB3 (rs5918), and NOS3 (rs2070744) were found to be associated with one or more blood lipids in at least one race/ethnic group in crude and adjusted analyses. In non-Hispanic whites, no individual polymorphisms were associated with any lipid trait. However, the PON1 A-G haplotype was significantly associated with LDL-C and TC. In non-Hispanic blacks, APOE variant rs7412 and haplotype T-T were strongly associated with LDL-C and TC; whereas, rs5918 of ITGB3 was significantly associated with TG. Several variants and haplotypes of three genes were significantly related to lipids in Mexican Americans: PON1 in relation to HDL-C; APOE and NOS3 in relation to LDL-C; and APOE in relation to TC. We report the significant associations of blood lipids with variants and haplotypes in APOE, ITGB3, NOS3, and PON1 in the three main race/ethnic groups in the U.S. population using a large, nationally representative and population-based sample survey. Results from our study contribute to a growing body of literature identifying key determinants of plasma lipoprotein concentrations and could provide insight into the biological mechanisms underlying serum lipid and cholesterol concentrations.BMC Medical Genetics 01/2010; 11:62. · 2.33 Impact Factor
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ABSTRACT: Many investigations have focused the association between TNF 308 G/A polymorphism and risk for type 2 diabetes mellitus (T2DM). However, the sample sizes of most of the studies were small. The aim of this study is to evaluate the precise association between this variant and risk for T2DM in a large-scale meta-analysis. All publications were searched on the association between TNF 308 G/A polymorphism and T2DM. The key words were as follows: diabetes, tumor necrosis factor and polymorphism/variant/genotype. This meta-analysis was assessed by Review manager 5.0. There were 18 studies identified. The odds ratios (ORs) and 95% confidence intervals (CI) for GA+AA versus GG genotype of TNF 308 G/A polymorphism were 1.03 (0.95-1.12), 1.03 (0.94-1.13) and 1.03 (0.78-1.36) in overall, Caucasian and Asian populations, respectively. The sensitivity analysis further strengthened the validity of this association. No publication bias or heterogeneity was observed in this study. In summary, there was no significant association detected between the TNF 308 G/A polymorphism and risk for T2DM.PLoS ONE 01/2011; 6(4):e18480. · 4.09 Impact Factor
Article: Association of TNF-α promoter gene G-308A polymorphism with metabolic syndrome, insulin resistance, serum TNF-α and leptin levels in Indian adult women.[show abstract] [hide abstract]
ABSTRACT: Tumour necrosis factor alpha is a multifunctional proinflammatory cytokine involved in the pathogenesis of metabolic syndrome, insulin resistance, and obesity. Aim of this study is to investigate in a North Indian female population the impact of the G-308A TNF-α variant on various components of the metabolic syndrome, Insulin Resistance, serum TNF-α and Leptin levels. The G-308A TNF-α polymorphism has been studied in 269 females with metabolic syndrome (NCEP ATP III criteria) (age 31.91±6.05) and 272 healthy females without metabolic syndrome (age 30.96±7.01). The G-308A variant was detected by PCR amplification and Nco-1 digestion. Homozygous mutant genotype (AA) (p=<0.001: OR=3.24: 95% CI=2.15-4.89) and mutant allele (A) (p=<0.001: OR=3.04: 95% CI=2.08-4.43) of TNF-α was significantly less frequently observed in the control population as compared to study group. Furthermore, on dividing the subjects into two groups according to the absence (TNF-1 allele) or presence of the mutant A (TNF-2) allele, significant results were obtained in most of the metabolic risk factors. Our results suggest that the G-308A polymorphism of the TNF-α gene may be independently associated with hypertension, leptin level and hypercholesterolemia leading to metabolic syndrome independent of Insulin resistance and hyperglycemia.Cytokine 05/2011; 57(1):32-6. · 3.02 Impact Factor