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Association of SLC30A8 rs1326634 Gene Variant with Central Fat Distribution in Overweight and Obese Women
Session:
SESSÃO DE POSTERS 26 - CARDIOGENÉTICA EM AÇÃO!
Speaker:
Ana Débora Câmara De Sá
Congress:
CPC 2025
Topic:
J. Preventive Cardiology
Theme:
28. Risk Factors and Prevention
Subtheme:
28.6 Obesity
Session Type:
Cartazes
FP Number:
---
Authors:
Ana Débora Câmara De Sá; Maria Isabel Mendonça; Francisco Sousa; Gonçalo Abreu; Matilde Ferreira; Sónia Freitas; Eva Henriques; Sofia Borges; Graça Guerra; António Drumond; Ana Célia Sousa; Roberto Palma Dos Reira
Abstract
<p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><strong>Introduction:</strong> Epidemiological studies suggest that the location and distribution of excess fat, rather than overall adiposity, provide better insights into the risk of cardiometabolic diseases. Fat distribution, often assessed through waist-to-hip ratio (WHR), has been shown to have a heritable component, with twin-based heritability estimates ranging from 30%-60% and narrow-sense heritability estimated at approximately 50% in women and only around 20% in men. However, which genetic factors influence fat distribution in overweight and obese women remain poorly understood.</span></span></p> <p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><strong>Aim: </strong>Assess the relationship between a set of single nucleotide polymorphisms previously associated with obesity and the WHR in overweight and obese women. </span></span></p> <p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><strong>Methods: </strong>A cohort study was conducted in<strong> </strong>512 women (aged 56.1 ± 6.4 years) with Body Mass Index (BMI) >25 kg/m2. Waist-to-Hip Ratio (WHR) was calculated as the ratio of waist circumference (measured at the narrowest point between the lower rib and the iliac crest) to hip circumference (measured at the widest point of the hips). Two groups were composed according WHR values: WHR >0.85 (android/central fat distribution) and WHR ≤0.85 (gynoid fat distribution). Fifteen single nucleotide polymorphisms previously linked to obesity and lipid metabolism abnormalities were genotyped using TaqMan real-time PCR. The association of these SNPs with WHR was achieved by bivariate and multivariate logistic regression analysis, and the dominant or recessive genetic model were considered for comparison.</span></span></p> <p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><strong>Results: </strong>After bivariate analysis, PSRC1 variant rs599839 (AA+GA vs GG) showed a significant association with android type obesity (OR=3.18; 95%CI 0.99-10.27; p=0.041), together with SLC30A8 rs1326634 (CC vs TT+TC) (OR=2.38; 95%CI 1.31-4.33; p=0.004). KIF6 rs20455 (TT vs CC+CT) showed an association with gynoid type obesity (OR=0.47; 95%CI 0.22-0.99; p=0.043) in bivariate analyses. After multivariate logistic regression with these three significant genes adjusted for the traditional risk factors, only SLC30A8 rs1326634 (CC vs TT+TC) that encodes the secretory granule-resident and largely endocrine pancreas-restricted zinc transporter ZnT8, remained in the equation as independently associated with an increased WHR (OR=2.50; 95%CI 1.37-4.57; p=0.003).</span></span></p> <p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><strong>Conclusion: </strong>A significant association between the SLC30A8 rs1326634 gene variant and android/central fat distribution was found in overweight and obese women. Understanding the genetic basis of obesity and central fat distribution can enable lifestyle changes or pharmacologic interventions to attenuate risk of cardiometabolic complications. </span></span></p>
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