Role of tumor necrosis factor-alpha gene locus in obesity and obesity-associated hypertension in French Canadians

Obesity represents a serious risk factor for the development of cardiovascu lar diseases, including hypertension. Segregation studies suggest that obes ity and obesity-associated hypertension may share some genetic determinants . The results of the present candidate gene investigation suggest that in h ypertensive pedigrees of French-Canadian origin, one such determinant is th e tumor necrosis factor (TNF)-alpha 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 (P=0.05 to 0.0004). Gender-separa te quantitative sib-pair analyses showed that the impact of the locus on ob esity is most significant in the abdominal region in men and in the thigh r egion in women. Furthermore, the haplotype relative-risk test demonstrated a significant association between the TNF-alpha gene locus and both obesity (P=0.006) and obesity-associated hypertension (P=0.02). These effects were most significant in individuals with nonmorbid obesity. In conclusion, the results of linkage and association analyses suggest that in hypertensive p edigrees of French-Canadian origin, the TNF-alpha gene locus contributes to the determination of obesity and obesity-associated hypertension. In addit ion, the data indicate that gender modifies the effect of the locus on the regional distribution of body fat.