TCF7L2 polymorphism rs7903146 is associated with coronary artery disease severity and mortality.

BACKGROUND: TCF7L2 polymorphisms have been consistently associated with type 2 diabetes mellitus in different populations and type 2 diabetes mellitus is a major risk factor for cardiovascular disease, especially coronary artery disease. This study aimed to evaluate the association between TCF7L2 polymorphism rs7903146 and coronary artery disease in diabetic and non-diabetic subjects. METHODS AND RESULTS: two populations were studied in order to assess severity of coronary artery disease and cardiovascular events incidence. Eight-hundred and eighty nine subjects who were referred for cardiac catheterization for coronary artery disease diagnosis were cross-sectionally evaluated for coronary lesions (atherosclerotic burden) and 559 subjects from the MASS-II Trial were prospectively followed-up for 5 years and assessed for major cardiovascular events incidence. As expected, rs7903146 T allele was associated with diabetes. Although diabetic patients had a higher prevalence of coronary lesions, no association between TCF7L2 genotype and coronary lesions was found in this subgroup. However, non-diabetic individuals carrying the T allele were associated with a significantly higher frequency of coronary lesions than non-diabetic non-carriers of the risk allele (adjusted OR = 2.32 95%CI 1.27-4.24, p = 0.006). Moreover, presence of multi-vessel coronary artery disease was also associated with the CT or TT genotypes in non-diabetics. Similarly, from the prospective sample analysis, non-diabetics carrying the CT/TT genotypes had significantly more composite cardiovascular end-points events than CC carriers (p = 0.049), mainly due to an increased incidence of death (p = 0.004). CONCLUSIONS: rs7903146 T allele is associated with diabetes and, in non-diabetic individuals, with a higher prevalence and severity of coronary artery disease and cardiovascular events. name of registry site (see list below), registration number, trial registration URL in brackets. CLINICAL TRIAL REGISTRATION INFORMATION: MEDICINE, ANGIOPLASTY, OR SURGERY STUDY (MASS II): Unique identifier: ISRCTN66068876.

Diabetes mellitus / Diabetes mellitus

O diabetes mellitus é uma síndrome de alterações metabólicas e hiperglicemia devido a uma deficiência absoluta ou relativa da secreção de insulina e/ou redução de sua eficácia biológica. Atualmente a classificação do diabetes inclui quatro síndromes possíveis: diabetes tipo 1 e tipo 2, diabetes gestacional e ainda algumas síndromes hiperglicêmicas causadas por outras situações específicas, como defeitos genéticos, insuficiência pancreática ou secundária a drogas como corticosteróides, anti-retrovirais e imunossupressores. Segundo critérios da Associação Americana de Diabetes, o diagnóstico pode dar-se de três formas: 1)glicemia de jejum superior ou igual a 126 mg/dL; 2) glicemia casual (independente do horário ou relação com a última refeição) acima de 200 mg/dL, quando associada a sintomas clássicos: poliúria, polidipsia e emagrecimento; 3) glicemia de 2h durante teste de tolerância oral à glicose (oGGT). O tratamento do diabético visa abaixar os níveis glicêmicos e controlar outros fatores de risco para redução das complicações circulatórias, para que possa haver melhora dos sintomas e normalização do estado nutricional.