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Browsing by Author "Guerra, G"

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  • Associação independente da variante rs1333049, no locus 9p21, com a doença coronária, numa população portuguesa
    Publication . Mendonça, Isabel; Reis, RP; Pereira, A; Café, H; Serrão, M; Sousa, AC; Freitas, AI; Guerra, G; Freitas, S; Freitas, C; Ornelas, I; Brehm, A; Araújo, JJ
    Introdução: Estudos recentes de associação genómica em larga escala (GWAS) identificaram vários polimorfismos de um único nucleótido (SNP), localizados no locus 9p21, associados com doença arterial coronária (DAC). De entre eles o SNP rs1333049 demonstrou uma associação consistente com a DAC tendo sido reproduzida, com sucesso, em várias populações. Objectivo: Investigar se a nova variante rs1333049, no cromossoma 9p21, é um factor de risco independente para DAC, na população Portuguesa. Material e métodos: Estudo caso-controlo, que incluiu 1406 indivíduos, 723 doentes coronários internados consecutivamente (idade média de 53,7±8,9 anos 79,9% do sexo masculino) e 683 controlos sem doença coronária (idade média de 53,3±10,5 anos, 73,9 % do sexo masculino) seleccionados para não serem significativamente diferentes quanto ao sexo e idade. Estudou-se o SNP rs1333049, em todos os indivíduos, com recurso à técnica convencionada de PCR combinada com a técnica TaqMan (Applied Biosystems). Determinou-se a distribuição alélica e genotípica (C/G), odds ratio e respectivo intervalo de confiança para risco de DAC. Foi construído um modelo de regressão logística forward wald ajustado para a idade, sexo, factores de risco convencionais, marcadores bioquímicos e genótipos em estudo, afim de avaliar quais as variáveis associadas de forma significativa e independente com DAC. Resultados: 60% dos doentes coronários e 53% dos controlos apresentaram o alelo C (OR=1,33; p=0,0002), 35,7% dos doentes e 29,3% dos controlos tinham o genótipo homozigoto CC (OR=1,34;p=0,010). O heterozigoto CG estava presente em 48,1% dos doentes e 47% nos controlos, não atingindo significância estatística, para risco vascular (OR=1,05;p=0,670). Após análise multivariada de regressão logística o genótipo CC do cromossoma 9p21 ficou na equação com um OR=1,7, p=0,018 e o genótipo heterozigoto CG com um OR=1,5, p=0,048. Conclusão: Com o presente trabalho replicou-se, numa população portuguesa, o risco coronário ligado à nova variante rs1333049 do cromossoma 9p21. A robustez deste genótipo, tanto em homo como em heterozigotia, tem sido consistente e relevante na estratificação de risco para a DAC, mesmo em contextos populacionais muito diversos. Nestas circunstâncias, a utilização do genótipo CC ou CG poderá vir a revelar-se útil para a previsão do risco de DAC na nossa população.
    2011-06Journal article Open access Show more
  • Association of ADAMTS7 gene polymorphism with cardiovascular survival in coronary artery disease
    Publication . Pereira, A; Palma dos Reis, R; Rodrigues, R; Sousa, A C; Gomes, S; Borges, S; Ornelas, I; Freitas, A I; Guerra, G; Henriques, E; Rodrigues, M; Freitas, S; Freitas, C; Brehm, A; Pereira, D; Mendonça, M I
    Recent genetic studies have revealed an association between polymorphisms at the ADAMTS7 gene locus and coronary artery disease (CAD) risk. Functional studies have shown that a CAD-associated polymorphism (rs3825807) affects ADAMTS7 maturation and vascular smooth muscular cell (VSMC) migration. Here, we tested whether ADAMTS7 (A/G) SNP is associated with cardiovascular (CV) survival in patients with established CAD. A cohort of 1,128 patients with angiographic proven CAD, who were followed up prospectively for a mean follow-up period of 63 (range 6-182) mo, were genotyped for rs3825807 A/G. Survival statistics (Cox regression) compared heterozygous (AG) and wild-type (AA) with the reference homozygous GG. Kaplan-Meier (K-M) survival curves were performed according to ADAMTS7 genotypes for CV mortality. Results showed that 47.3% of patients were heterozygous (AG), 36.5% were homozygous for the wild-type allele (AA) and only 16.2% were homozygous for the GG genotype. During the follow-up period, 109 (9.7%) patients died, 77 (6.8%) of CV causes. Survival analysis showed that AA genotype was an independent risk factor for CV mortality compared with reference genotype GG (HR = 2.7, P = 0.025). At the end of follow-up, the estimated survival probability (K-M) was 89.8% for GG genotype, 82.2% for AG and 72.3% for AA genotype (P = 0.039). Carriage of the mutant G allele of the ADAMTS7 gene was associated with improved CV survival in patients with documented CAD. The native overfunctional ADAMTS7 allele (A) may accelerate VSMC migration and lead to neointimal thickening, atherosclerosis progression and acute plaque events. ADAMTS7 gene should be further explored in CAD for risk prediction, mechanistic and therapeutic goals.
    2016-09-09Journal article Open access Show more
  • Genetic polymorphisms and coronary artery disease in the portuguese population: the GENEMACOR Study
    Publication . Pereira MD PHDs, A; Mendonca, M; Neto, M; Rodrigues, R; Monteiro, Joel; Sousa, A C; Rodrigues, M; Guerra, G; Borges, S; Palma dos Reis, R
    Multiple studies have showed an association between genetic polymorphisms and the risk of coronary artery disease (CAD). Initially, studies focused mainly in variants acting in pathophysiological axis of CAD or its risk factors. Genome-Wide Association Studies (GWAS) revealed other genes that, besides having an unknown mechanism, are statistically significant. The importance of these in the development of CAD in the Portuguese population is unknown. Objective: Analyze the genetic polymorphisms associated with the development of CAD in a Portuguese population. Methods: We performed a case-control study with 1321 consecutive coronary patients (mean age 53.4 ± 8.1 years, 78.8% male) and 1148 controls (adjusted for age and sex) selected from GENEMACOR Study, an ongoing study designed to analyze the genetic profile of a Portuguese population. We evaluated, in both groups, 29 genetic variants previously associated with CAD: ACE I/D, AGT235 M/T, ATIR A/C, MTHFR C/T and 1298 A/C, PON192 Q/R and 55 L/M,LPA T/C, APO E, Locus 9p21.3 (rs1333049), CDKN2B (rs4977574), GJA4 C/T, PCSK9 A/G, TAS2R50 A/G, KIF6 C/T, IGF2BP2 G/T, ADAMTS7 A/G, MC4R T/C, PPARG Pro12 Ala, ZNF259 C/G, SMAD3 C/T, MIA3 C/A, MTHFD1L A/G, SLC30A8 C/T, TCF7L2 C/T, HNF4 C/G, FTO A/C and ADIPOQ C/G. Allele and genotypic frequencies of individuals with and without CAD were compared and the strength of association was expressed by the OR as well as by CI 95%. Results: The variants rs4340 (ACE I/D), rs266729 (ADIPOQ C/G), rs458560 (PON55 L/M), rs429358 (APOE2), LPA T/C, rs1333049 (locus 9p21.3) and rs4977574 (CDKN2B A/G) were significantly associated with CAD (p<0.05) (Table). Conclusions: In our population, the genetic polymorphisms significantly related to CAD were: ACE, associated with hypertension; ADIPOQ, associated with obesity; PON55, associated with oxidation; APOE and LPA, associated with dyslipidemia and finally the locus 9p21.3 with a unclear mechanism so far.
    2017Conference object Open access Show more