Role of Tumor Necrosis Factor-α Gene Locus in Obesity and Obesity-Associated Hypertension in French Canadians

Abstract

Abstract-Obesity represents a serious risk factor for the development of cardiovascular diseases, including hypertension.Segregation studies suggest that obesity and obesity-associated hypertension may share some genetic determinants. The results of the present candidate gene investigation suggest that in hypertensive pedigrees of French-Canadian origin, one such determinant is the tumor necrosis factor (TNF)-␣ gene locus. Gender-pooled quantitative sib-pair analysis demonstrated a significant effect of the gene locus on 3 global and 7 regional measures of obesity (Pϭ0.05 to 0.0004).Gender-separate quantitative sib-pair analyses showed that the impact of the locus on obesity is most significant in the abdominal region in men and in the thigh region in women. Furthermore, the haplotype relative-risk test demonstrated a significant association between the TNF-␣ gene locus and both obesity (Pϭ0.006) and obesity-associated hypertension (Pϭ0.02). These effects were most significant in individuals with nonmorbid obesity. In conclusion, the results of linkage and association analyses suggest that in hypertensive pedigrees of French-Canadian origin, the TNF-␣ gene locus contributes to the determination of obesity and obesity-associated hypertension. In addition, the data indicate that gender modifies the effect of the locus on the regional distribution of body fat. (Hypertension. 2000;36:14-19.)

Weight gain in relation to plasma levels of complement factor 3: results from a population-based cohort study

“…For example, TNF-α and IL1-β decrease the production and expression of leptin, an anorexigenic hormone formed in the adipose tissue [32]. Polymorphisms of the genes encoding TNF-α receptor have been associated with leptin-resistance and obesity [33,34]. In studies of rodents, injection of TNF-α and IL-1 initially reduces food intake.…”

Promoter polymorphism in the macrophage migration inhibitory factor gene is associated with obesity

“…Indeed, gene polymorphisms of TNF have been associated with obesity by many investigators. [24][25][26][27][28][29][30][31] Infiltrative macrophages have been shown to be increased and to be the main source of TNF-a expression in adipose tissue in obese mice. 32,33 MIF could upregulate TNF-a secretion by macrophages.…”

Association studies of genetic polymorphisms in central obesity: a critical review

“…13 By contrast, only a few of these studies give sufficient attention to phenotypes reflecting central obesity (eg abdominal visceral fat, WHR, waist circumference, sagittal abdominal diameter). Table 1 54,55 peroxisome proliferative activated receptor g, coactivator 1 (PPARGC1), 56 tumor necrosis factor (TNF), 57,58 tumor necrosis factor receptor superfamily, member 1B (TNFRSF1B), 59 uncoupling protein 2 (UCP2), 60 and uncoupling protein 3 (UCP3). 61 In addition to the positive association studies summarized in Table 1, the number of 'negative' reports, which are only partly reviewed below, is also increasing very rapidly.…”

“…104,105 Some, but not all studies, have indicated a key role for the À308 variant of the TNF gene in the pathogenesis of obesity and obesity-associated insulin resistance. [57][58][59][106][107][108][109][110][111] However, only four of these studies include anthropometric indices of central obesity. 57,58,110,111 Among these studies, two reported associations between the GÀ308A variant of the TNF and measurements of central obesity.…”

“…[57][58][59][106][107][108][109][110][111] However, only four of these studies include anthropometric indices of central obesity. 57,58,110,111 Among these studies, two reported associations between the GÀ308A variant of the TNF and measurements of central obesity. 57,58 In one of the negative studies, men homozygous for the A allele had a trend toward greater central adiposity and higher insulin and glucose levels.…”