Sex Difference Impacts on the Relationship between Paraoxonase-1 (PON1) and Type 2 Diabetes
Valentina Rosta,
Alessandro Trentini,
Angelina Passaro,
Giovanni Zuliani,
Juana Maria Sanz,
Cristina Bosi,
Gloria Bonaccorsi,
Tiziana Bellini,
Carlo Cervellati
Affiliations
Valentina Rosta
Department of Biomedical and Specialist Surgical Sciences, Section of Medical Biochemistry, Molecular Biology and Genetics, University of Ferrara, 44121 Ferrara, Italy
Alessandro Trentini
Department of Biomedical and Specialist Surgical Sciences, Section of Medical Biochemistry, Molecular Biology and Genetics, University of Ferrara, 44121 Ferrara, Italy
Angelina Passaro
Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, 44121 Ferrara, Italy
Giovanni Zuliani
Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, 44121 Ferrara, Italy
Juana Maria Sanz
Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, 44121 Ferrara, Italy
Cristina Bosi
Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, 44121 Ferrara, Italy
Gloria Bonaccorsi
Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, 44121 Ferrara, Italy
Tiziana Bellini
Department of Biomedical and Specialist Surgical Sciences, Section of Medical Biochemistry, Molecular Biology and Genetics, University of Ferrara, 44121 Ferrara, Italy
Carlo Cervellati
Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, 44121 Ferrara, Italy
Type-2 diabetes (T2D) and its cardiovascular complications are related to sex. Increasing evidence suggests that paraoxonase 1 (PON1) activity, an antioxidant enzyme bound to high-density lipoproteins (HDL), is implicated in the onset and clinical progression of T2D. Since we previously showed that PON1 is a sexual dimorphic protein, we now investigated whether sex might impact the relationship between PON1 and this chronic disease. To address this aim, we assessed PON1 activity in the sera of 778 patients, including controls (women, n = 383; men, n = 198) and diabetics (women, n = 79; men = 118). PON1 activity decreased in both women and men with T2D compared with controls (p p > 0.001, respectively), but the change was 50% larger in the female cohort. In line with this result, the enzyme activity was associated with serum glucose level only in women (r = −0.160, p = 0.002). Notably, only within this gender category, lower PON1 activity was independently associated with increased odds of being diabetic (odds ratio (95% Confidence interval: 2.162 (1.075–5.678)). In conclusion, our study suggests that PON1-deficiency in T2D is a gender-specific phenomenon, with women being more affected than men. This could contribute to the partial loss of female cardiovascular advantage associated with T2D.
