title: Study of genetic variation in the STAT3 on obesity and insulin resistance in male adults.
abstract: Signal transducer and activator of transcription 3 (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 analyzed three tagging single-nucleotide polymorphisms (tagSNPs), two intronic (rs2293152 and rs6503695) and one located in a noncoding region near the gene promoter (rs9891119). These variants were not associated with either 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 BMI as a continuous trait (P values: 0.85, 0.73, and 0.58 for rs2293152, rs6503695, and rs9891119, respectively). We found no significant association between the three tagSNPs and fasting plasma glucose and insulin. Likewise, no association was observed between the homeostasis model assessment (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.
authors.affiliation: Molecular Genetics and Biology of Complex Diseases Department, Institute of Medical Research, A. Lanari, University of Buenos Aires-CONICET, Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: Tomas F
authors.initials: TF
authors.lastname: Gianotti
authors.forename: Silvia
authors.initials: S
authors.lastname: Sookoian
authors.forename: Carolina
authors.initials: C
authors.lastname: Gemma
authors.forename: Adriana L
authors.initials: AL
authors.lastname: Burgueño
authors.forename: Claudio D
authors.initials: CD
authors.lastname: González
authors.forename: Carlos J
authors.initials: CJ
authors.lastname: Pirola
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D015992:Body Mass Index; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005215:Fasting / Q000097:blood; D020022:Genetic Predisposition to Disease; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics*; D007438:Introns; D008297:Male; D009765:Obesity / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011159:Population Surveillance; D012307:Risk Factors; D050796:STAT3 Transcription Factor / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: D001786:Blood Glucose; D007328:Insulin; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human