Several previous studies suggested an association between p.Thr92Ala polymorphism and hypertension , bipolar disorder , mental retardation , low intelligence quotient (IQ), recovery from lung injury , osteoarthritis , increased bone turnover , Grave’s and Hashimoto’s diseases . To our knowledge no studies were focused on patients with obesity and, in particular on subjects affected by severe obesity (median of BMI 44.8 Kg/m2) undergoing to bariatric surgery. We investigated the DIO2 p.Thr92Ala polymorphism in relation to obesity and its comorbidities in a group of patients submitted to bariatric surgery. The prevalence of DIO2 p.Thr92Ala polymorphism observed (11.5% Ala/Ala homozygous variant) was similar to that reported in the general European population (14.1% Ala/Ala homozygous variant) and in the Tuscany population (11.2% Ala/Ala homozygous variant) , excluding a possible role of the p.Thr92Ala polymorphism in promoting the onset of severe obesity. Similar results were observed in a relatively large population-based cohort of whites in which DIO2 p.Thr92Ala genotype was evaluated in patients with and without obesity . When a dominant or a recessive model for the penetrance of Ala92 allele were used, no association with obesity was detected [16, 18, 19]. On the contrary, other published studies reported a significant association between p.Thr92Ala polymorphism and BMI, but only when patients without obesity were evaluated . Moreover a correlation was observed only in patients with both p.Thr92Ala and p.Trp64Arg ADRB3 polymorphisms [4, 18]. This interaction was not replicated in studies on the Pima Indians  and in another large cohort of more than 7000 Danish white subjects . In our study an early-onset of severe obesity was significantly associated with DIO2 polymorphism. In details, the mean age at bariatric surgery was 45.4±11.3 years in wild type patients, 41.1±10.8 years in patients with rare homozygous variant (Ala/Ala) and 44.6±11.5 in heterozygous Thr/Ala patients (p=0.03). These results support a possible role of DIO2 p.Thr92Ala polymorphism in contributing to early-onset of severe obesity, although we do not believe that this is a major determinant for obesity among our study population. To our knowledge no published studies evaluated the association between obesity-related comorbidities and p.Thr92Ala polymorphism. We did not found any association between p.Thr92Ala polymorphism and the presence of obesity-related comorbidities such as diabetes mellitus, liver steatosis, and sleep apnoea syndrome or metabolic syndrome. Surprisingly, a higher rate of hypertension was observed in wild type patients. Published studies in which the association between the DIO2 p.Thr92Ala polymorphism and glycemic control in T2DM patients has been explored, reported contradictory results [2, 3, 19, 25]. Nevertheless, a recent meta-analysis found that people who are homozygous for p.Thr92Ala had 4.8% higher HbA1C levels, suggesting that Ala/Ala homozygosity may be associated with worse glycemic control in T2DM patients . Differently to our results, Gumieniak et al reported that the Ala allele increases the risk for development of arterial hypertension . In disagreement with these results no differences were observed in the prevalence of hypertension among the genotypes (Ala/Ala, Thr/Ala, Thr/Thr; 76.4%, 79.1%, 75.7% respectively, p=0.785) when 315 patients with diabetes mellitus were analyzed . These apparently conflicting findings might be partially explained by differences in the studied population. In Gumieniak’s report, T2DM patients were excluded and subjects were younger than those included in the study of Canani [10, 27]. Bariatric surgery is currently the most effective tool in determining an important and lasting weight loss in patients with obesity; in addition a high rate of remission of the main obesity-related comorbidities has been reported after bariatric surgery [28–34]. In our study, bariatric surgery was effective, in terms of weight loss (EWL%) in all patients, regardless the genotype. Moreover, bariatric surgery promotes remission or a significant improvement of obesity related comorbidities without significant differences between the three groups.