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Lam SY, Mommersteeg MC, Yu B, et al. Toll-like receptor 1 locus re-examined in a genome-wide association study update on anti-Helicobacter pylori IgG titers. Gastroenterology. 2022;doi: 10.1053/j.gastro.2022.01.011.
Lam, S. Y., Mommersteeg, M. C., Yu, B., Broer, L., Spaander, M. C. W., Frost, F., Weiss, S., Völzke, H., Lerch, M. M., Schöttker, B., Zhang, Y., Stocker, H., Brenner, H., Levy, D., Hwang, S. J., Wood, A. C., Rich, S. S., Rotter, J. I., Taylor, K. D., Tracy, R. P., Kabagambe, E. K., Leja, M., Klovins, J., Peculis, R., Rudzite, D., Nikitina-Zake, L., Skenders, G., Rovite, V., Uitterlinden, A., Kuipers, E. J., Fuhler, G. M., Homuth, G., & Peppelenbosch, M. P. (2022). Toll-like receptor 1 locus re-examined in a genome-wide association study update on anti-Helicobacter pylori IgG titers. Gastroenterology, . https://doi.org/10.1053/j.gastro.2022.01.011
Lam, Suk Yee, et al. "Toll-like receptor 1 locus re-examined in a genome-wide association study update on anti-Helicobacter pylori IgG titers." Gastroenterology vol. (2022). doi: https://doi.org/10.1053/j.gastro.2022.01.011
Lam SY, Mommersteeg MC, Yu B, Broer L, Spaander MCW, Frost F, Weiss S, Völzke H, Lerch MM, Schöttker B, Zhang Y, Stocker H, Brenner H, Levy D, Hwang SJ, Wood AC, Rich SS, Rotter JI, Taylor KD, Tracy RP, Kabagambe EK, Leja M, Klovins J, Peculis R, Rudzite D, Nikitina-Zake L, Skenders G, Rovite V, Uitterlinden A, Kuipers EJ, Fuhler GM, Homuth G, Peppelenbosch MP. Toll-like receptor 1 locus re-examined in a genome-wide association study update on anti-Helicobacter pylori IgG titers. Gastroenterology. 2022 Jan 11; doi: 10.1053/j.gastro.2022.01.011. Epub 2022 Jan 11. PMID: 35031300.
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Gastroenterology. 2022 Jan 11; doi: 10.1053/j.gastro.2022.01.011. Epub 2022 Jan 11.

Toll-like receptor 1 locus re-examined in a genome-wide association study update on anti-Helicobacter pylori IgG titers.

Gastroenterology

Suk Yee Lam, Michiel C Mommersteeg, Bingting Yu, Linda Broer, Manon C W Spaander, Fabian Frost, Stefan Weiss, Henry Völzke, Markus M Lerch, Ben Schöttker, Yan Zhang, Hannah Stocker, Hermann Brenner, Daniel Levy, Shih-Jen Hwang, Alexis C Wood, Stephen S Rich, Jerome I Rotter, Kent D Taylor, Russell P Tracy, Edmond K Kabagambe, Marcis Leja, Janis Klovins, Raitis Peculis, Dace Rudzite, Liene Nikitina-Zake, Girts Skenders, Vita Rovite, André Uitterlinden, Ernst J Kuipers, Gwenny M Fuhler, Georg Homuth, Maikel P Peppelenbosch

Affiliations

  1. Department of Gastroenterology & Hepatology, Erasmus University Medical Center Rotterdam, The Netherlands.
  2. Department of Internal Medicine, Erasmus University Medical Center Rotterdam, The Netherlands.
  3. Department of Medicine A, University Medicine Greifswald, Greifswald, Germany.
  4. Department of Medicine A, University Medicine Greifswald, Greifswald, Germany; Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany.
  5. Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
  6. Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany; Network Aging Research, Heidelberg University, Heidelberg, Germany.
  7. Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany.
  8. The Framingham Heart Study, National Heart, Lung, and Blood Institute's, Framingham, MA, USA; The Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD, USA.
  9. USDA/ARS Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX, USA.
  10. Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.
  11. The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA USA.
  12. Laboratory for Clinical Biochemistry Research, The University of Vermont, College of Medicine, Colchester VT, USA.
  13. Division of Academics, Ochsner Health, New Orleans, LA, USA.
  14. Institute of Clinical and Preventive Medicine & Faculty of Medicine University of Latvia, Riga, Latvia.
  15. Latvian Biomedical Research and Study Centre, Riga, Latvia.
  16. R?ga Stradi?š University, Riga, Latvia.
  17. Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany.
  18. Department of Gastroenterology & Hepatology, Erasmus University Medical Center Rotterdam, The Netherlands. Electronic address: [email protected].

PMID: 35031300 DOI: 10.1053/j.gastro.2022.01.011

Abstract

BACKGROUND AND AIMS: A genome-wide significant association between anti-Helicobacter pylori (H. pylori) IgG titers and Toll-like receptor (TLR1/6/10) locus on 4p14 was demonstrated for individuals of European ancestry, but not uniformly replicated. We re-investigate this association in an updated genome-wide association study (GWAS) meta-analysis for low gastric cancer incidence populations, address potential causes of cohort heterogeneity and explore functional implications of genetic variation at the TLR1/6/10 locus.

METHODS: The dichotomous GWAS (25% individuals exhibiting highest anti-H. pylori IgG titers versus remaining 75%) included a discovery and replication sample of respectively n=15,685 and n=9,676, all of European ancestry. Longitudinal analysis of serological data was performed on H. pylori-eradicated subjects (n=132) and patients under surveillance for premalignant gastric lesions (n=107). TLR1/6/10 surface expression, TLR1 messenger RNA (mRNA) and cytokine levels were measured in leukocyte subsets of healthy subjects (n=26) genotyped for TLR1/6/10 variants.

RESULTS: The association of the TLR1/6/10 locus with anti-H. pylori IgG titers (rs12233670; β=-0.267 SE±0.034; P=4.42x10

CONCLUSION: The association between anti-H. pylori IgG titers and TLR1/6/10 locus was not replicated across cohorts, possibly due to dependency of anti-H. pylori IgG titers on therapy, clearance and antibody decay. H. pylori-mediated immune cell activation is partly mediated via TLR1 signaling, which in turn is affected by genetic variation.

Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.

Keywords: Polymorphism; Single Nucleotide; bacteria; immunity; serology

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