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Curso de Atualização em Medicina Cardiovascular 2019
Reunião Anual Conjunta dos Grupos de Estudo de Cirurgia Cardíaca, Doenças Valvulares e Ecocardiografia da SPC
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Genetic variation at the ADAMTS7 locus and smoking interaction in CAD progression
Session:
Posters 4 - Écran 7 - Prevenção
Speaker:
Joel Monteiro
Congress:
CPC 2019
Topic:
O. Basic Science
Theme:
36. Basic Science
Subtheme:
36.3 Basic Science - Cardiac Diseases
Session Type:
Posters
FP Number:
---
Authors:
Joel Ponte Monteiro; Maria Isabel Mendonça; Andreia Pereira; Joao Adriano Sousa; Flávio Mendonça; Micaela Rodrigues Neto; Joel Monteiro; Ana Célia Sousa; Eva Henriques; Mariana Rodrigues; Ana Isabel; Ilídio Ornelas; A. Drumond de Freitas; Roberto Palma dos Reis
Abstract
<p>Complex gene-environment interactions are at the origin and development of Coronary Disease. Recent studies have demonstrated that allelic variation A>G at ADAMTS7 rs3825807 locus, is associated with reduced gene expression and confer stronger CAD protection.</p> <p><strong>Aim</strong>: Investigate the cardio-protection demonstrated by ADAMTS7 rs3825807 GG genotype versus AA+GA, throughout the evolution of CAD, in our non-smoking coronary population and whether, in the smoking population, this effect disappears or is attenuated.</p> <p><strong>Methods:</strong> A total of 1607 coronary patients were selected from GENEMACOR Study: 853 non-smokers (55.4 ±7.4 years; 70% male) and 754 smokers (50.9 ± 8 years; 89%). ‘Smoking status’ refers to current smokers or subjects with less than 5 years of smoking cessation. Genotyping was performed using the TaqMan Real-Time PCR method for ADAMTS7 AA, AG and GG. The patient’s survival was evaluated according to the genetic variation A> G (GG versus AA + GA). The probability of survival was estimated through a Kaplan-Meier analysis.</p> <p><strong>Results:</strong> After a maximum follow-up period of 12 years, in the non-smoking population, the mutated GG genotype showed a survival probability of 88.1%, whereas the genotypes (AA + AG) with the non-mutated allele presented 81.2% survival. The Log-Rank test showed significant differences between the two curves (p=0.015). In the smoking population, the protective effect of the mutation was maintained in the GG genotype (survival probability=79%), but the wild-type (AA +AG) presented worse survival (69.1%) (curves cross each other, and Breslow test did not reach significance p=0.075). In the smoking population, the survival curves start to diverge only after 8 years of follow- up.</p> <p><strong>Conclusion: The GG genotype of</strong> ADAMTS7 decreases survival in CAD patients. The environmental factor (smoking) interacts with the genetic variation of the polymorphism ADAMTS7 A<G, interfering with the mechanisms involved in CAD progression. Inhibition of ADAMTS7 can represent a novel potential therapeutic strategy for CAD that may have particular benefit in individuals who smoke cigarettes.</p>
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