TY - JOUR

T1 - The additive contribution from inflammatory genetic markers on the severity of cardiovascular disease

AU - Berg, K K

AU - Madsen, Hans Ole

AU - Garred, P

AU - Wiseth, R

AU - Gunnes, S

AU - Videm, V

N1 - Keywords: Coronary Disease; Female; Genetic Markers; Genetic Predisposition to Disease; Humans; Inflammation; Interleukin-6; Linkage (Genetics); Male; Middle Aged; Polymorphism, Genetic; Pulmonary Surfactant-Associated Protein D; Toll-Like Receptor 4

PY - 2009

Y1 - 2009

N2 - Inflammation plays a key role in the development of atherosclerosis. Genetic differences in molecules related to inflammation have therefore been linked to the susceptibility for and severity of atherosclerosis. We hypothesized that the additive contribution from different genes of importance for inflammation would enhance the severity of cardiovascular disease. Blood samples were collected from 230 adults admitted for elective coronary angiography. A total of 130 patients had significant (>50%) stenosis in at least one main coronary artery branch and 100 had not. Six polymorphisms in five different genes were analysed: myeloperoxidase (MPO) -129G/A and -463G/A, toll-like receptor 4 (TLR4) Asp299Gly, interleukin-6 (IL6) -174G/C, surfactant protein D (SFTPD) Met11Thr and regulated upon normal T-cell expressed and secreted (CCL5) -403G/A. The IL6 polymorphism was significantly associated (P = 0.017) to angiographic significant coronary artery disease, and this relation remained after adjustment for age, gender, smoking and hypercholesterolaemia (P = 0.007). The TLR4 (P = 0.050) and SFTPD (P = 0.058) polymorphisms were also associated with the presence of coronary stenosis in univariate but not in multivariate analyses. For MPO and CCL5 no associations were found. There was a significant linear association between the number of high-risk gene variants (IL6-174CC, SFTPD 11CC and TLR4 299AA) and the proportion of patients with coronary artery disease (P < 0.0005). Inherited factors related to inflammation may increase susceptibility for severe coronary artery disease. Furthermore, the additive contribution from different inflammatory genetic markers strongly enhances the individual severity of cardiovascular disease.

AB - Inflammation plays a key role in the development of atherosclerosis. Genetic differences in molecules related to inflammation have therefore been linked to the susceptibility for and severity of atherosclerosis. We hypothesized that the additive contribution from different genes of importance for inflammation would enhance the severity of cardiovascular disease. Blood samples were collected from 230 adults admitted for elective coronary angiography. A total of 130 patients had significant (>50%) stenosis in at least one main coronary artery branch and 100 had not. Six polymorphisms in five different genes were analysed: myeloperoxidase (MPO) -129G/A and -463G/A, toll-like receptor 4 (TLR4) Asp299Gly, interleukin-6 (IL6) -174G/C, surfactant protein D (SFTPD) Met11Thr and regulated upon normal T-cell expressed and secreted (CCL5) -403G/A. The IL6 polymorphism was significantly associated (P = 0.017) to angiographic significant coronary artery disease, and this relation remained after adjustment for age, gender, smoking and hypercholesterolaemia (P = 0.007). The TLR4 (P = 0.050) and SFTPD (P = 0.058) polymorphisms were also associated with the presence of coronary stenosis in univariate but not in multivariate analyses. For MPO and CCL5 no associations were found. There was a significant linear association between the number of high-risk gene variants (IL6-174CC, SFTPD 11CC and TLR4 299AA) and the proportion of patients with coronary artery disease (P < 0.0005). Inherited factors related to inflammation may increase susceptibility for severe coronary artery disease. Furthermore, the additive contribution from different inflammatory genetic markers strongly enhances the individual severity of cardiovascular disease.

U2 - 10.1111/j.1365-3083.2008.02187.x

DO - 10.1111/j.1365-3083.2008.02187.x

M3 - Journal article

C2 - 19140875

VL - 69

SP - 36

EP - 42

JO - Scandinavian Journal of Immunology, Supplement

JF - Scandinavian Journal of Immunology, Supplement

SN - 0301-6323

IS - 1

ER -