Genetic variation in the stress protein hsp70-2 gene is highly associated with obesity

BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) expression is increased in adipose tissue of both rodent models of obesity and obese humans. It has therefore been considered as a candidate gene for obesity. Several studies have indeed shown statistical evidence of linkage between obesity and the chromosomal region encompassing the TNF-alpha gene, suggesting that TNF-alpha and/or a nearby gene (eg hsp70 gene) is involved in the onset and progression of weight gain. We designed a case-controlled study to investigate the potential association of polymorphism of the TNF-alpha and that of a stress protein (hsp70-2) with obesity. METHODS: We used the polymerase chain reaction and restriction enzyme digestion to characterize the variation of the TNF-alpha promoter region and that of the hsp70-2 gene in 343 unrelated Tunisian patients with obesity and 174 healthy control subjects. RESULTS: Analysis of the -308 TNF-alpha polymorphism in patients with obesity and in control subjects did not reveal an association between TNF-alpha alleles and obesity. In contrast, polymorphism analysis of the hsp70-2 gene in patients with obesity demonstrated highly significant differences in genotypic distribution of this bi-allelic locus compared to the control subject group. Homozygosity for one hsp70-2 allele was highly associated with obesity (r(2) = 7.12; P < 10(-6)). CONCLUSION: Tunisian persons carrying the P2/P2 genotype of the hsp70-2 gene may have an increased risk of obesity.