Allelic frequency of G380A polymorphism of tumor necrosis factor alpha gene and relation with cardiovascular risk factors and adipocytokines in obese patients

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Abstract

Background: The aim of our study was to investigate the allelic frequency of the G308A polymorphism in the TNF alpha gene and the influence of G308A this polymorphism on cardiovascular risk factors and adipokine levels in obese patients. Design: A population of 834 obesity patients was analyzed. A nutritional evaluation and a blood analysis were performed. The statistical analysis was performed for the combined G308A and A308A as mutant group and type G308G as wild group. Results: A total of 630 patients (181 males/449 females) (75.5%) had the genotype G308/G308 (wild genotype group) with an average age of 43.5 ± 14.8 years, 188 patients (61 males/127 females) (22.5%) had the genotype G308/A308 (mutant genotype group-heterozygote) and 16 patients (5 males/11 females) (1.9%) with an average age of 44.5 ± 14.2 years had the genotype A308/A308 (mutant group-homorozygote) with an average age of 44.3 ± 11.4 years, without statistical differences in the mean age or sex distribution. Genotypes G308/A308 and A308/A308 was designed (mutant genotype group) as a dominant model. Allelic frequency of the A substitucion -308 was 13.19%. Anthropometric, adipokines, insulin resistance, lipid levels ad dietary intake were similar in both genotypes. Conclusion: In conclusion, allelic frequency of G308A polymorphism is is in accordance with allelic frequencies observed in other populations. Carries of A308 allele have the same anthropometric and metabolic profile than wild type carriers.

Translated abstract

Antecedentes: El objetivo de nuestro estudio fue investigar la frecuencia alélica del polimorfismo G308A del gen TNF alfa y su influencia en los factores de riesgo cardiovascular y los niveles de adipocinas en pacientes obesos. Diseño: Se estudió una población de 834 pacientes obesos. Se realizaron una evaluación nutricional y un análisis de sangre. El análisis estadístico se realizó para el genotipo combinado G308A y A308A como grupo de mutantes y G308G tipo de grupo salvaje. Resultados: Un total de 630 pacientes (181 varones/449 mujeres) (75,5%) tenían el genotipo G308/G308 (grupo con genotipo salvaje) con una edad media de 43,5 ± 14,8 años, 188 pacientes (61 varones/127 mujeres) (22,5%) con una edad media de 44,5 ± 14,2 años tuvieron el G308/A308 genotipo (grupo de mutantes genotipo heterocigoto) y 16 pacientes (5 varones/11 mujeres) (1,9%) tuvieron la A308/A308 genotipo (mutante grupo homorozygote) con una edad media de 44,3 ± 11,4 años, sin encontrar diferencias en la edad media o la distribución por sexo. La frecuencia alelica de la substitucion A-308 fue 13,19%. Las variables antropométricas, adipoquinas, resistencia a la insulina, perfil lípidico y la ingesta dietética fueron similares en ambos genotipos. Conclusión: En conclusión, la frecuencia alélica del polimorfismo G308A está de acuerdo con las frecuencias alélicas observadas en otras poblaciones. Los obesos portadores del alelo A308 tienen los mismos perfiles antropométricos y metabólicos que los pacientes obesos con el genotipo salvaje.

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Most cited references 44

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Role of adiponectin in preventing vascular stenosis. The missing link of adipo-vascular axis.

Ryozo Nagai, Yoshihisa Okamoto, Shinji Kihara … (2002)

Obesity is more linked to vascular disease, including atherosclerosis and restenotic change, after balloon angioplasty. The precise mechanism linking obesity and vascular disease is still unclear. Previously we have demonstrated that the plasma levels of adiponectin, an adipose-derived hormone, decreases in obese subjects, and that hypoadiponectinemia is associated to ischemic heart disease. In current the study, we investigated the in vivo role of adiponectin on the neointimal thickening after artery injury using adiponectin-deficient mice and adiponectin-producing adenovirus. Adiponectin-deficient mice showed severe neointimal thickening and increased proliferation of vascular smooth muscle cells in mechanically injured arteries. Adenovirus-mediated supplement of adiponectin attenuated neointimal proliferation. In cultured smooth muscle cells, adiponectin attenuated DNA synthesis induced by growth factors including platelet-derived growth factor, heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF), basic fibroblast growth factor, and EGF and cell proliferation and migration induced by HB-EGF. In cultured endothelial cells, adiponectin attenuated HB-EGF expression stimulated by tumor necrosis factor alpha. The current study suggests an adipo-vascular axis, a direct link between fat and artery. A therapeutic strategy to increase plasma adiponectin should be useful in preventing vascular restenosis after angioplasty.

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Functional analysis of linker-scan mutants spanning the -376, -308, -244, and -238 polymorphic sites of the TNF-alpha promoter.

J Bayley, H de Rooij, P van den Elsen … (2001)

Tumor necrosis factor alpha (TNF-alpha) promoter polymorphisms have been linked to a large number of diseases but studies examining the possible direct functional effects of these polymorphisms have been contradictory. Previous studies compared TNF-alpha promoter constructs containing single nucleotide changes. We have now made a series of mutant constructs in which regions of the TNF-alpha promoter containing suspected functional single nucleotide polymorphisms, including -376, -308, -244 and -238, were replaced by a 10 bp linker scan sequence. These constructs were transiently transfected into the T cell line Jurkat, the B cell line Raji, and the monocytic cell line U937, and tested for basal and induced transcriptional activity. Mutant constructs covering both the -308 and -376 polymorphisms showed no significant differences in either basal or induced transcriptional activity. Constructs covering the -244/-238 region showed a small increase in basal activity in the U937 cell line. These results indicate (i) that the -308 and -376 regions are of no functional relevance for TNF-alpha promoter transcription, and (ii) that the -244/-238 region does not influence transcription in some cell lines but may have some role in transcription in others. Copyright 2001 Academic Press.

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Association of the TNF-alpha -308 G/A promoter polymorphism with insulin resistance in obesity.

Ian D. Caterson, J. Bryson, A Gosby … (2002)

Obesity is a major risk factor for the development of type 2 diabetes. Tumor necrosis factor (TNF)-alpha is a candidate gene for the development of both obesity and insulin resistance. We investigated whether a common polymorphism in the promoter region (-308 G/A) of the TNF-alpha gene was associated with increased risk for the development of insulin resistance and cardiovascular disease in an obese Australian population. Obese, non-diabetic subjects (146 women and 34 men) were genotyped with polymerase chain reaction-restriction fragment length polymorphism techniques, and anthropometric and biochemical measurements were analyzed. A homeostasis model assessment (HOMA) score was used to gauge the level of insulin resistance. The frequencies of the G allele and the A allele were 0.759 and 0.241, respectively. Subjects homozygous for the A allele had higher fasting insulin levels (226 vs. 131 pM; p < 0.001), higher HOMA scores (10.2 vs. 5.3; p < 0.001), higher systolic blood pressure (143 vs. 129 mm Hg; p = 0.02), and lower high-density lipoprotein (HDL) cholesterol (1.13 vs. 1.25 mM; p = 0.04) than did subjects homozygous for the G allele. Whereas an association between insulin resistance and body mass index or waist circumference was seen in all subjects, a highly significant negative correlation of HDL cholesterol to HOMA scores (r = -0.710; p < 0.001) occurred in subjects with the A allele only. The -308 G/A TNF-alpha gene variant conveys an increased risk for the development of insulin resistance in obese subjects. The presence of low HDL cholesterol levels further increases the risks associated with insulin resistance in carriers of the A allele.

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Author and article information

Contributors

D. A. De Luis: Role: ND

R. Aller: Role: ND

O. Izaola: Role: ND

M. González Sagrado: Role: ND

R. Conde: Role: ND

B. de la Fuente: Role: ND

H. F. Ovalle: Role: ND

Journal

Journal ID (publisher-id): nh

Title: Nutrición Hospitalaria

Abbreviated Title: Nutr. Hosp.

Publisher: Grupo Arán (Madrid, Madrid, Spain )

ISSN (Print): 0212-1611

ISSN (Electronic): 1699-5198

Publication date (Print and electronic): August 2011

Volume: 26

Issue: 4

Pages: 711-715

Affiliations

[01] orgnameUniversity of Valladolid orgdiv1Medicine School and Unit of Investigation orgdiv2Center of Investigation of Endocrinology and Nutrition Spain

[02] Valladolid orgnameHospital Rio Hortega Spain