Association of TGFB1 rs1800469 and BCMO1 rs6564851 with coronary heart disease and IL1B rs16944 with all-cause mortality in men from the Northern Ireland PRIME study

Abstract

Background Historically, high levels of morbidity and mortality have been associated with cardiovascular disease in the Northern Ireland population. Previously reported associations between single nucleotide polymorphisms (SNPs) and cardiovascular disease within other populations have not always been consistent. Objective To investigate associations between 33 SNPs with fatal or non-fatal incident coronary heart disease (CHD) events and all-cause mortality in the Northern Irish participants of the Prospective Epidemiological Study of Myocardial Infarction (PRIME). Method Phase 2 of the PRIME study prospectively evaluated 2,010 men aged 58–74 years in Northern Ireland for more than 10 years for incident CHD events (myocardial infarction, percutaneous coronary intervention, coronary artery bypass, and cardiac death) and more than 15 years for all-cause mortality. SNPs previously reported in association with cardiovascular outcomes were evaluated against incident CHD events and all-cause mortality using Cox’s proportional hazards models adjusted for established cardiovascular disease risk factors. Results During the follow-up period, 177 incident CHD events were recorded, and 821 men died. Both BCMO1 rs6564851 (Hazard ratio [HR] = 0.76; 95% confidence intervals [CI]: 0.60–0.96; P = 0.02) and TGFB1 rs1800469 (HR = 1.30; CI: 1.02–1.65; P = 0.04) were significantly associated with incident CHD events in adjusted models. Only IL1B rs16944 was significantly associated with all-cause mortality (HR = 1.18; CI: 1.05–1.33; P = 0.005). No associations remained significant following Bonferonni correction for multiple testing. Conclusion We report a novel association between BCMO1 rs6564851 and risk of incident CHD events. In addition, TGFB1 rs1800469 and IL1B rs16944 were associated with the risk of incident CHD events and all-cause mortality outcomes respectively, supporting previously reported associations.

Genótipo da Paraoxonase-1 e Angiograma Positivo para Doença Arterial Coronariana

“…Exemplos de polimorfismos de genes incluem o efeito de polimorfismos (M235T e T174M) no gene do angiotensinogênio (AGT), TGFB1 rs1800469 e BCMO1 rs6564851. 2 - 3 Pesquisas futuras devem examinar as implicações de variantes genéticas inesperadas e possivelmente desconcertantes.…”

“…Examples of gene polymorphisms include the effect of polymorphisms (M235T and T174M) on the angiotensinogen gene (AGT), TGFB1 rs1800469, and BCMO1 rs6564851. 2 - 3 Future research should examine the implications of unexpected, possibly perplexing genetic variants.…”