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Association of the CYP17A1 Gene With the Development of Insulin Resistance
Session:
Sessão de Posters 44 - Miscelânea: genética, estratificação de risco e mecânica miocárdica
Speaker:
Cláudia C. Sousa
Congress:
CPC 2026
Topic:
O. Basic Science
Theme:
36. Basic Science
Subtheme:
36.6 Basic Science - Other
Session Type:
Posters Eletrónicos
FP Number:
---
Authors:
Cláudia C. Sousa; Ana Célia Sousa; Carolina Olim; Alexandra Rodrigues; Vasco Nunes; Mariana Rodrigues; Ana Cardoso; Graça Guerra; Sofia Borges; Maria João Oliveira; Maria Isabel Mendonça; Roberto Palma Dos Reis
Abstract
<p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,"sans-serif""><strong>Introdução:</strong> Insulin resistance (IR) is a major cardiovascular risk marker, thus the investigation of genetic and environmental determinants essential. Although multiple genetic variants have been linked to IR, the role of the <em>CYP17A1</em> gene remains poorly explored. The Metabolic Score for Insulin Resistance (METS-IR) is a validated, practical, and non-invasive surrogate marker of insulin resistance.</span></span></p> <p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,"sans-serif""><strong>Objective:</strong> Investigate the association between <em>CYP17A1</em> and insulin resistance assessed by METS-IR.</span></span></p> <p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,"sans-serif""><strong>Methods:</strong> 1,765 adults (mean age 51.0±8.4 years) were evaluated and underwent biochemical testing and DNA sampling for <em>CYP17A1</em> genotyping. METS-IR was calculated using the formula: </span></span><span style="font-size:11pt"><span style="font-family:Calibri,"sans-serif"">ln[2×fasting blood glucose (FBG) + triglycerides (TG)]×body mass index (BMI) / ln [High Density Lipoprotein-Cholesterol (HDL-C) <span style="font-family:"Calibri","sans-serif"">]</span>. </span></span><span style="font-size:11pt"><span style="font-family:Calibri,"sans-serif"">Genetic inheritance models (dominant, additive, and recessive) were tested against METS-IR; the dominant model showed the best fit. The association between <em>CYP17A1</em> and METS-IR was tested by Mann-Whitney<strong>. </strong> A multivariable regression assessed whether the<em> CYP17A1</em> dominant model remained independently associated with METS-IR increase after adjustment for hypertension, physical inactivity, alcohol consumption, and smoking.</span></span></p> <p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,"sans-serif""><strong>Results:</strong> Mann-Whitney test showed that carriers of the <em>CYP17A1</em> (CT+CC) presented significantly higher METS-IR values (p=0.022). Multivariable regression showed that <em>CYP17A1 </em>(CT+CC), hypertension, physical inactivity, and alcohol consumption were independent predictors of METS-IR, with statistical significance (p<0.0001). Individuals carrying the C allele exhibited METS-IR scores 1.17-fold higher than TT.</span></span></p> <p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,"sans-serif""><strong>Conclusions:</strong> The <em>CYP17A1</em> polymorphism (CT+CC) is significantly and independently associated with insulin resistance in this population. Individuals with this risk variant may benefit from personalized lifestyle interventions to prevent insulin-resistance progression and reduce future cardiovascular risk.</span></span></p>
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