Background: Toll-like receptor 4 (TLR4), the signalling receptor for lipopolysaccharides, is
an important member of the innate immunity system. Since several studies have suggested
that atherosclerosis might be associated with changes in the innate immune response,
and a SNP in the TLR4 gene (Asp299Gly; Kiechl et al, N Engl J Med 2002;347:185–92)
was shown to be associated with a decreased risk of atherosclerosis, we sought to
investigate the impact of gene variants in the TLR4 gene on incident CHD. Methods: A case-cohort study was conducted in initially healthy, middle-aged men and women
based on data from the MONICA/KORA Augsburg studies collected between 1984 and 2002,
with a mean FU of 10.2±4.8 years. The present analyses are based on 318 case subjects
with incident CHD and 1,727 non-case subjects. Seven SNPs (rs2770150; rs6478317; rs1927911;
rs2149356; rs4986791; rs7873784; rs1927906) were systematically selected in the TLR4
gene, and haplotypes were constructed. Results: TLR4 genotype distribution did not significantly differ among subjects with incident
CHD and non-case subjects. No significant interactions between any of the SNPs and
major cardiovascular risk factors on CHD risk were found. There was no consistent
association between the 7 different SNPs within the TLR4 gene and incident CHD in
crude and in multivariable adjusted analyses, neither for men and women separately,
nor in a model that included all study participants. Conclusions: In contrast to an earlier and smaller prospective study, we could not confirm an
association between various SNPs within the TLR4 gene and incident CHD. The presence
of various alleles of the TLR4 gene, including Asp299Gly, does not seem to exert a
major influence on the progression of atherosclerosis in the general population.
