Toll-like receptor 4 rs11536889 is associated with angiographic extent and severity of coronary artery disease in a Chinese population

Toll-like receptor 4 (TLR4) is a key modulator in many inflammation-related diseases. Polymorphisms in the TLR4 gene may alter TLR4 expression and affect the extent and severity of coronary artery disease (CAD). We analyzed 3 polymorphisms of TLR4 in 607 Chinese subjects who underwent coronary arteriography. Blood samples were collected to identify the polymorphisms. We evaluated the relationships between the polymorphisms and the number of vessels involved in coronary stenosis, Gensini scores, and Duke prognostic scores. We found that rs11536889 was associated with an increased risk of 3-vessel disease. When subjects with 3-vessel disease were compared to subjects with nonsignificant CAD, rs11536889 variant genotypes were associated with an increased risk of 3-vessel disease (GC/ CC vs. GG: OR=2.06, 95%CI=1.21-3.51). When subjects with 3-vessel disease were compared to subjects with 1-vessel disease, rs11536889 variant genotypes were associated with an increased risk of 3-vessel disease (GC vs. GG: OR=2.14, 95% CI=1.20-3.79; GC/ CC vs. GG: OR=2.06, 95% CI=1.20-3.54). When subjects with 3-vessel disease were compared to subjects with non-3-vessel disease, rs11536889 variant genotypes were associated with an increased risk of 3-vessel disease (GC vs. GG: OR=1.76, 95% CI=1.12-2.75; GC/ CC vs. GG: OR=1.83, 95% CI=1.19-2.82). The TLR4 rs11536889 polymorphism was also related to Gensini score (P=0.02). The Gensini score was higher in subjects with the variant CC and GC/ CC genotype than in subjects with the wild GG genotype (61.28 +/- 1.84 and 57.64 +/- 34.82 vs. 51.27 +/- 34.57). Our results demonstrate that TLR4 rs11536889 polymorphism is a novel genetic factor in the development of CAD, influencing the extent and severity of CAD.