Study of Genetic Variation in the STAT3 on Obesity and Insulin Resistance in Male Adults.

FERNANDEZ GIANOTTI T; SOOKOIAN S; DIEUZEIDE G; GARCIA SI; GEMMA C; GONZALEZ CD; PIROLA CJ

Obesity (Silver Spring, ex Obesity Research)

Nature Publishing Group.

Lugar: London, United Kindom; Año: 2008 vol. 16 p. 1702 - 1707

1930-7381

STAT3 plays an important role in hepatic glucose homeostasis and carbohydrate metabolism and has been implicated in the leptin-mediated energy homeostasis. We explored whether STAT3 gene variants are associated with obesity and insulin resistance in a well-characterized sample of 984 adult men (aged 34.4±8.6 years) of self-reported European ancestry from a population-based study. We analysed 3 tagSNPs, 2 intronic (rs2293152 and rs6503695) and one located in a non-coding region near the gene promoter (rs9891119). These variants were not associated either with obesity (in which 488 lean individuals were compared to 496 overweight/obese subjects) (P values: 0.68, 0.49 and 0.9 for rs2293152, rs6503695 and rs9891119, respectively) or body mass index as continuous trait (P values: 0.85, 0.73 and 0.58 for rs2293152, rs6503695 and rs9891119, respectively). We found no significant association between the 3 tagSNPs and fasting plasma glucose and insulin. Likewise, no association was observed between the HOMA index and any of the tagSNPs. A significant association was observed with total cholesterol and rs6503695 (nominal P value 0.019), but after correcting for multiple testing by Bonferroni correction, the significance becomes marginal (p=0.057). In conclusion, although STAT3 is an excellent candidate gene for assessing obesity and insulin resistance susceptibility alleles, our results do not support a major role for STAT3 variants in BMI and insulin resistance in our male population.