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 (r2=7.12; P<10(-6)).


CONCLUSIONS
Tunisian persons carrying the P2/P2 genotype of the hsp70-2 gene may have an increased risk of obesity.
Chouchane
L
L
Laboratoire d'Immuno-Oncologie Moléculaire, Faculté de Médecine de Monastir, Monastir, Tunisia. lotfi.chouchane@planet.tn
Danguir
J
J
Beji
C
C
Bouassida
K
K
Camoin
L
L
Sfar
H
H
Gabbouj
S
S
Strosberg
A D
AD
D000328:Adult; D016022:Case-Control Studies; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D009765:Obesity / Q000209:etiology / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D015183:Restriction Mapping; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D018840:HSP70 Heat-Shock Proteins; C091879:HSPA2 protein, human; D014409:Tumor Necrosis Factor-alpha