Vol.:(0123456789) 1 3 Acta Diabetologica https://doi.org/10.1007/s00592-018-1277-x LETTER TO THE EDITOR A common polymorphism in MIR155 gene promoter region is associated with a lower risk to develop type 2 diabetes Andrea Latini 1  · Vincenza Spallone 2  · Cinzia D’Amato 2  · Giuseppe Novelli 1  · Paola Borgiani 1  · Cinzia Ciccacci 1 Received: 15 November 2018 / Accepted: 12 December 2018 © Springer-Verlag Italia S.r.l., part of Springer Nature 2019 Dear Editor, We read with great interest the paper “Polymorphisms in genes encoding miR-155 and miR-146a are associated with protection to type 1 diabetes mellitus” by Assmann et al. [1]. The authors described the association between two polymor- phisms in MIR155 and MIR146A genes and susceptibility to type 1 diabetes. It is known that these miRNAs are involved in immunity and inflammation pathways; therefore, it is con- ceivable that they could also play a role in type 2 diabetes mellitus (T2DM) susceptibility. In a previous publication, we had investigated MIR146a rs2910164 polymorphism in relation to T2DM susceptibility but we did not observe sig- nificant differences of frequencies between T2DM patients and healthy controls [2]. Since, at present time, there are no data in literature related to the effect of MIR155 polymorphisms in the sus- ceptibility to T2DM, we examined the MIR155 rs767649 (A/T) in 233 patients with T2DM recruited from outpatients attending the Diabetic Clinic of the Policlinico Tor Vergata (PTV) in Rome and 303 ethnically and age-matched healthy controls. DNA was extracted from peripheral blood and the polymorphism was genotyped using TaqMan Genotyping Assay (Thermo Fisher Scientific, Foster City, CA, USA). A case/control association study and a genotype/phenotype correlation analysis have been performed using the SPSS program (SSPS Inc., IL, USA). In Table 1a, we reported the distribution of genotypes and alleles frequencies in patients with T2DM and in the healthy controls. No subject homozygous for the low fre- quency A allele was observed. As shown, we observed a significant association between the rs767649 polymorphism and T2DM susceptibility. Individuals heterozygous for this genetic variant showed a lower risk to develop T2DM in comparison with wild-type individuals (OR 0.55, P = 0.029). The lower risk was observed also at the allelic level (OR 0.58 and P = 0.035). Therefore, the A allele seems to play a protective role for the development of T2DM, similarly to what observed in type 1 diabetes [1]. Subsequently, we performed a genotype/phenotype cor- relation analysis between the MIR155 polymorphism and clinical characteristics of patients with T2DM (Table 1b). Interestingly, the A allele of rs767649 polymorphism was significantly less frequent in patients with central obesity (OR 0.29, P = 0.039), suggesting a protective effect also for this condition. Conversely, we observed that the same geno- type was associated with a significantly increased risk to develop coronary artery disease (CAD) (OR 3.49, P = 0.02). The rs767649 polymorphism is located in the promoter region of gene encoding miR-155 and was reported to be able to alter transcriptional activity of this miRNA [3]: specifically, the A allele upregulates the mir expression. Dysregulation of the miR-155 has been observed in several inflammatory diseases, such as cardiovascular or autoim- mune diseases. Since one of the pathophysiological derange- ments of diabetes is chronic inflammation, an altered level of miR-155 caused by rs767649 A allele could explain the association. Decreased serum levels of miR-155 have been previously observed in obese patients [4]; on the contrary, CAD patients showed a higher miR-155 expression level when compared to control subjects [5]. Thus, the lower and higher frequencies of the A allele that we found in associa- tion with central obesity and CAD, respectively, seem to be consistent with the data of lower and higher miR-155 Managed By Massimo Porta. This comment refers to the article available online at https://doi. org/10.1007/s00592-016-0961-y. * Cinzia Ciccacci cinziaciccacci@libero.it 1 Department of Biomedicine and Prevention, Genetics Section, University of Rome “Tor Vergata”, 00133 Rome, Italy 2 Department of Systems Medicine, Endocrinology, University of Rome “Tor Vergata”, Rome, Italy