Tumor necrosis factor-alpha-238 and -308 polymorphisms do not associated with traits related to obesity and insulin resistance.

Walston, Jeremy D.; Seibert, Michael; Yen, Chung‐Jen; Cheskin, Lawrence J.; Andersen, Ross E.

doi:10.2337/diabetes.48.10.2096

Cited by 84 publications

(77 citation statements)

References 8 publications

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“…8,9 To our knowledge, this is the first study to report that the A allele of the TNFA -238 polymorphism is associated with a greater body fat % than the GG genotype. We demonstrated this effect in black women, as well as in the combined black and white group, independent of ethnicity.…”

Section: Discussionmentioning

confidence: 99%

“…1,7 The functional -308 G4A polymorphism within the promoter region of the TNFA gene is in close proximity to the TNFA -238 G4A polymorphism (rs361525). Although a number of studies have investigated the TNFA -308 G4A polymorphism, only a few have reported on the TNFA -238 G4A polymorphism and obesity, 8,9 and to our knowledge only one study has investigated the interaction between dietary fat intake and this polymorphism on adiposity and serum lipid concentrations. 2 However, there are no studies that have explored these associations in healthy populations of different ethnicity.…”

Section: Introductionmentioning

confidence: 99%

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The tumor necrosis factor-α gene -238 G>A polymorphism, dietary fat intake, obesity risk and serum lipid concentrations in black and white South African women

et al. 2012

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BACKGROUND/OBJECTIVES: This study explored interactions between dietary fat intake and the tumor necrosis factor-a gene (TNFA) -238 G4A polymorphism (rs361525) on adiposity and serum lipid concentrations in apparently healthy premenopausal black and white South African (SA) women. SUBJECTS/METHODS: Normal-weight (N ¼ 107) and obese (N ¼ 120) black, and normal-weight (N ¼ 89) and obese (N ¼ 62) white SA women underwent measurements of body composition, fasting lipids and dietary intake, and were genotyped for the -238 G4A polymorphism. RESULTS: Black women had a higher -238 GA genotype frequency than white women (Po0.001), but there were no differences between body mass index groups. Black women with the -238 A allele had a greater body fat % than those with the GG genotype (Po0.001). Further, in black women, with increasing polyunsaturated:saturated fat ratio and omega-6 (n-6):omega-3 (n-3) ratio, high-density lipoprotein-cholesterol (HDL-C) concentrations decreased, and total cholesterol (T-C):HDL-C ratio increased in those with the GA genotype but not the GG genotype. In addition, with increasing n-3 polyunsaturated fatty acid intake (percentage of total energy intake, %E), T-C:HDL-C ratio decreased in those with the GA genotype, but not in those with the GG genotype. In white SA women, with increasing eicosapentaenoic acid (%E) intake, low-density lipoprotein-cholesterol concentrations decreased in those with the GG genotype but not the GA genotype. CONCLUSIONS: The -238 G4A polymorphism was associated with body fatness in black women. Interactions between -238 G4A genotypes and dietary fat intake on serum lipids and adiposity differed depending on dietary fat intake, but those for serum lipids were not the same in black and white SA women.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The tumor necrosis factor-α gene -238 G>A polymorphism, dietary fat intake, obesity risk and serum lipid concentrations in black and white South African women

et al. 2012

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“…The genotype frequencies did not deviate from Hardy ± Weinberg equilibrium, and the frequency of the G allele (0.18) was similar to that described in a previous study (0.17) in Caucasians. 17 To examine whether the variant alleles were more common in patients with morbid obesity, we strati®ed the BErG participants by BMI quartiles (I,`27.3 kgam 2 ; II, 27.3 ± 31.9 kgam 2 ; III, 31.9 ± 36.5 kgam 2 ; IV, b 36.5 kgam 2 , in each quartile n 44; Table 2). w 2 analyses revealed a signi®cant difference in gene frequencies across the four grades of BMI (all groups P 0.013; extremes (IaIV) P 0.009, w 2 10.8, OR 3.29, Figure 1).…”

Section: Resultsmentioning

confidence: 99%

Tumor necrosis factor-α−308 G/A polymorphism in obese Caucasians

et al. 2001

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OBJECTIVE: Tumor necrosis factor-a (TNF-a) is expressed primarily in adipocytes, and elevated levels of this cytokine have been linked to obesity and insulin resistance. Recently, the A allele of a polymorphism in the 5H -¯anking region of the TNF-a gene (G7308A) has been reported to be more frequent in obese than in lean subjects and has also been associated with increased expression of this cytokine in fat tissue and in¯uences fat mass and insulin resistance. We, therefore, examined the relationship between this variant and obesity in a German Caucasian population. SUBJECTS AND METHODS:We genotyped 176 index subjects recruited within the framework of the BErG (Berlin Erna Èhrung Geschwister)-Study for the TNF-a-G7308A polymorphism. Subjects were characterized for weight, height, waist and hip circumference, body mass index (BMI), body composition, glucose tolerance, leptin and angiotensinogen levels. RESULTS: The frequency of the 7308A allele (0.18) was similar to that reported previously and genotype distribution was in Hardy ± Weinberg equilibrium (GG, n 118; GA, n 53; AA, n 5). There was a signi®cant difference in allele frequencies of the polymorphism by BMI quartiles (I,`27.3 kgam 2 ; II, 27.3 ± 31.9 kgam 2 ; III, 31.9 ± 36.5 kgam 2 ; IV, b 36.5 kgam 2 , in each quartile n 44) with 7308A allele carriers having a higher BMI than G allele carriers (P 0.013). Despite previous smaller studies that have related insulin resistance to the G7308A polymorphism, we found no relationship between glucose and insulin response during an oral glucose tolerance test (OGTT) and the polymorphism. Furthermore, none of the plasma parameters were related to the polymorphism. CONCLUSION: Our ®ndings support the hypothesis that the G7308A polymophism of the TNF-a gene is associated with BMI. The G7308A polymorphism may, therefore, represent a genetic marker for increased susceptibility for obesity in Caucasians.

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“…There was also strong negative association between 308 A allele and S. HDL-cholesterol, although insulin resistance was positively associated with BMI and waist circumference (WC) in all obese irrespective of G or A allele in obese Australians [45]. No significant differences by polymorphism carrier status were found for insulin resistance in Australian females [46], in diabetic Japanese patients [29,47], in Danish Caucasians [30], in obese Americans [48], in young healthy relatives of type 2 diabetic German Caucasians [49], in Hong Kong Chinese [50], in obese and lean Romans [51] and in overweight IGT Finnish subjects [20]. This association was neither found in relatives of type 2 diabetic British Caucasians and in controls [52] …”

Section: Tnf-alpha G308a Polymorphism and Insulin Resistancementioning

confidence: 99%

Inter-Ethnic Variations in Association of TNF-Alpha G308a Single Nucleotide Polymorphism with Type 2 Diabetes Mellitus - A Review

Nadeem¹

2017

JDMDC

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SummaryAccording to World Health Organization, the prevalence of diabetes mellitus (DM) is on the rise. Tissue necrosis factor-alpha (TNF-α) is one of the inflammatory markers which play role in the pathogenesis of DM. Single nucleotide polymorphism (SNP) at 308G/A has been reported to be associated with type 2 DM. Frequency of TNF-α G308A polymorphism was determined in different ethnic groups and is found to be highly variable. Limited number of studies reported a positive association between type 2 DM and TNF-α SNP and many studies; including metaanalyses failed to find such association. TNF-α G308A polymorphism has been found to be associated with insulin resistance and BMI, although these findings are challenged by many studies. The probable explanation of higher BMI is the association of presence of TNF-α G308A polymorphism with higher rates of lipid synthesis, and suppression of FFA levels in obese persons. There is no single explanation for such highly variable results in different ethnic groups. Presence of yet unidentified gene polymorphism in linkage disequilibrium with TNF-α gene polymorphism could be responsible. The different results can also be contributed to the fact that the study groups differ in age, gender distribution, age of onset of disease, life style, degree of obesity and glucose tolerance. Comprehensive genetic studies of whole TNF-alpha promoter area are required to be done in large population samples in different ethnic groups. Polymorphisms are usually co-related in a complex manner and are co-inherited and conclusions are difficult to be drawn on small sample size. Keywords: Inter-Ethnic Variations in Association of TNF-Alpha G308a Single Nucleotide Polymorphism with Type 2 Diabetes Mellitus -A Review 2/7Copyright: ©2017 Nadeem et al. directly inhibits insulin signaling by phosphorylation at serine 307 residue of IRS-1. It also induces transcription factor nuclear factor (NF)-kappa B which causes apoptosis of beta cell of pancreas. TNF-α also increases elevated serum free fatty acids (FFA) levels [4]. Local inflammation in obese adipose tissue was first reported in 2003 [1]. Elevated serum levels of TNF-α are found in type 2 DM patients and in obese healthy persons who subsequently developed type 2 DM in a span of 2-4 years indicating the future risk of metabolic syndrome and type 2 DM [3,[5][6][7]. Adipocytes contribute almost all of TNF-α and explain the association of high TNF-α level with obesity and raised body mass index [7,8]. Indirect studies also indicate exercise and weight loss can lead to decreased concentration of 9]. High levels of TNF-α have been reported to be associated with insulin resistance [9][10][11]. TNF α renders insulin resistance by interfering with insulin signaling in adipocytes and hepatocytes. TNF-α causes insulin resistance in skeletal muscle too by impairing glucose uptake and translocation of glucose uptake transporters (GLUT-4) [12]. Hyperinsulinemia itself induces augmented production of TNF-α in serum in obese type 2 DM patients [9][10][11][12][1...

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Tumor necrosis factor-alpha-238 and -308 polymorphisms do not associated with traits related to obesity and insulin resistance.

Cited by 84 publications

References 8 publications

The tumor necrosis factor-α gene -238 G>A polymorphism, dietary fat intake, obesity risk and serum lipid concentrations in black and white South African women

The tumor necrosis factor-α gene -238 G>A polymorphism, dietary fat intake, obesity risk and serum lipid concentrations in black and white South African women

Tumor necrosis factor-α−308 G/A polymorphism in obese Caucasians

Inter-Ethnic Variations in Association of TNF-Alpha G308a Single Nucleotide Polymorphism with Type 2 Diabetes Mellitus - A Review

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