Association between arterial thrombosis and the promoter polymorphism (-260c/t) of the monocyte lipopolysaccharide receptor, CD14

Yoko Yatabe, Daisuke Ito, Norio Tanahashi, Yasuo Fukuuchi, Mie Tanaka, Shiro Iwanaga, Satoshi Ogawa, Ikuo Saito, Akira Sonoda, Atsumi Ohta, Eiko Takeshita, Mitsuru Murata, Yasuo Ikeda, Kiyoaki Watanabe

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Abstract

An initial phase of atherosclerosis involves the migration of monocyte-derived macrophages to the subendothelial space. Monocytes are stimulated by lipopolysaccharides (LPS), which are internalized by the cells through the CD14 antigen (LPS receptor). Recent papers suggest that a genetic variation in the promoter region of the CD14 antigen gene is associated with myocardial infarction (MI). Subjects with the 260T/T genotype, who reportedly have a higher CD14 antigen expression on the monocyte surface than those with T/C or C/C genotypes, might be at risk for MI. The present study analyzed the genotype and allele frequencies of the 260C/T polymorphism for patients with ischemie cerebrovascular disease (CVD), MI, and angina pectoris in the Japanese population. CD14 antigen levels on the monocyte surface (mCD14) were analyzed by flow-cytometry, and serum levels of soluble CD14 (sCD14) by enzyme-linked immunosorbent assay. We recruited 235 patients with CVD (age 59.0 ±3.6 y) as confirmed by brain CT and/or MRI, and 309 age- and gender-matched controls for CVD (age 58.3 ±7.8 y). We also recruited 163 patients with angiographically-proven coronary artery disease (CAD, 82 MI and 81 angina pectoris, age 58.7 ±8.1 y) and 210 age- and gender-matched controls for CAD (age 59.8 ±3.8 y). The control subjects were all healthy volunteers who had no history of stroke or any type of cardiovascular disease with normal resting electrocardiograms. The allele frequencies of our control subjects were different from those reported for Caucasian controls; i.e., 0.52 for 260C and 0.48 for 260T (reported frequencies for Caucasians are 0.65 for -260C and 0.35 for 260T, Hubacek et al., 1999). There was no difference, however, in the genotype distribution between our CVD patients and controls (patients: 24.3%, 53.2%, and 22.6%: controls: 26.9%, 50.2%, and 23.0%, for C/C, C/T, and T/T genotypes, respectively), or between CAD patients and controls. The 260C/T genotype was not associated with serum levels of sCD14 in CVD patients (4.28 ±0.82, 4.62 ±1.05, and 4.76 ±1.23 \igjm\ for C/C, C/T, and T/T, respectively, p=0.358), nor was it associated with surface mCD14 (343 ±61, 287 ±83, and 313 ±70 units, respectively, p=0.238). These results suggest racial differences in the genotype frequency of the 260C/T polymorphism and that this genetic variation has no major impact on stroke or CAD in the Japanese population.

Original languageEnglish
Pages (from-to)104b
JournalBlood
Volume96
Issue number11 PART II
Publication statusPublished - 2000 Dec 1

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Yatabe, Y., Ito, D., Tanahashi, N., Fukuuchi, Y., Tanaka, M., Iwanaga, S., Ogawa, S., Saito, I., Sonoda, A., Ohta, A., Takeshita, E., Murata, M., Ikeda, Y., & Watanabe, K. (2000). Association between arterial thrombosis and the promoter polymorphism (-260c/t) of the monocyte lipopolysaccharide receptor, CD14. Blood, 96(11 PART II), 104b.