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Genetic variants in TLR2 and TLR4 are associated with markers of monocyte activation: the Atherosclerosis Risk in Communities MRI Study

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Abstract

Markers of monocyte activation play a critical role in atherosclerosis, but little is known about the genetic influences on cellular levels. Therefore, we investigated the influence of genetic variants in monocyte differentiation antigen (CD14), toll-like receptor-4 (TLR4), toll-like receptor-2 (TLR2), and myeloperoxidase (MPO) on monocyte surface receptor levels. The study sample consisted of 1,817 members of a biracial cohort of adults from the Atherosclerosis Risk in Communities Carotid MRI Study. Monocyte receptors were measured using flow cytometry on fasting whole blood samples. TLR2 rs1816702 genotype was significantly associated with CD14+/TLR2+ percent of positive cells (%) and median fluorescence intensity (MFI) in whites but not in blacks (p < 0.001). Specifically, the presence of the minor T-allele was associated with increased receptor levels. In blacks, TLR4 rs5030719 was significantly associated with CD14+/TLR4+ monocytes (MFI) with mean ± SE intensities of 16.7 ± 0.05 and 16.0 ± 0.14 for GG and GT/TT genotypes, respectively (p < 0.001). Variants in TLR2 and TLR4 were associated with monocyte receptor levels of TLR2 and TLR4, respectively, in a biracial cohort of adults. To our knowledge, this is the first study to look at associations between variants in the toll-like receptor family and toll-like receptor levels on monocytes.

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Acknowledgments

The Atherosclerosis Risk in Communities (ARIC) Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, and N01-HC-55022. The ARIC MRI Study was supported by U01-HL075572 from the National Heart, Lung, and Blood Institute. The investigators thank the participants and staff in the ARIC Study for their important contributions.

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Authors and Affiliations

  1. Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Harwick Building 6-56, 200 First Street South West, Rochester, MN, 55909, USA

    Suzette J. Bielinski

  2. Department of Medicine Developmental Biology Center, Lillehei Heart Institute, University of Minnesota, Minneapolis, MN, USA

    Jennifer L. Hall

  3. Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, USA

    James S. Pankow & Aaron R. Folsom

  4. Human Genetics Center, University of Texas-Houston Health Science Center, Houston, TX, USA

    Eric Boerwinkle

  5. Division of Hematology, University of Texas Health Science Center, San Antonio, TX, USA

    Nena Matijevic-Aleksic

  6. Department of Biostatistics, School of Public Health, University of North Carolina, Chapel Hill, NC, USA

    Max He & Lloyd Chambless

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  1. Suzette J. Bielinski
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Correspondence to Suzette J. Bielinski.

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Bielinski, S.J., Hall, J.L., Pankow, J.S. et al. Genetic variants in TLR2 and TLR4 are associated with markers of monocyte activation: the Atherosclerosis Risk in Communities MRI Study. Hum Genet 129, 655–662 (2011). https://doi.org/10.1007/s00439-011-0962-4

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