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Association of TIM-1 (T-Cell Immunoglobulin and Mucin Domain 1) With Incidence of Stroke

  • Lu Song
  • Jiangming Sun
  • Martin Söderholm
  • Olle Melander
  • Marju Orho-Melander
  • Jan Nilsson
  • Yan Borné
  • Gunnar Engström
Publishing year: 2020
Language: English
Pages: 1777-1786
Publication/Series: Arteriosclerosis, Thrombosis, and Vascular Biology
Volume: 40
Issue: 7
Document type: Journal article
Publisher: Lippincott Williams Wilkins Hagerstown, MD

Abstract english

OBJECTIVE: The aim of this study was to investigate if there is a causal relationship between circulating levels of TIM-1 (T-cell immunoglobulin and mucin domain 1) and incidence of stroke. Approach and Results: Plasma TIM-1 was analyzed in 4591 subjects (40% men; mean age, 57.5 years) attending the Malmö Diet and Cancer Study. Incidence of stroke was studied in relation to TIM-1 levels during a mean of 19.5 years follow-up. Genetic variants associated with TIM-1 (pQTLs [protein quantitative trait loci]) were examined, and a 2-sample Mendelian randomization analysis was performed to explore the role of TIM-1 in stroke using summary statistics from our pQTLs and the MEGASTROKE consortium. A total of 416 stroke events occurred during follow-up, of which 338 were ischemic strokes. After risk factor adjustment, TIM-1 was associated with increased incidence of all-cause stroke (hazards ratio for third versus first tertile, 1.44 [95% CI, 1.10-1.87]; P for trend, 0.004), and ischemic stroke (hazards ratio, 1.42 [95% CI, 1.06-1.90]; P for trend, 0.011). Nineteen independent lead SNPs, located in three genomic risk loci showed significant associations with TIM-1 (P<5×10-8). A 2-sample Mendelian Randomization analysis suggested a causal effect of TIM-1 on stroke (β=0.083, P=0.0004) and ischemic stroke (β=0.102, P=7.7×10-5). CONCLUSIONS: Plasma level of TIM-1 is associated with incidence of stroke. The genetic analyses suggest that this could be a causal relationship.


  • Cardiac and Cardiovascular Systems
  • diabetes mellitus
  • incidence
  • mendelian randomization analysis
  • risk factor
  • stroke
  • TIM-1


  • Cardiovascular Research - Translational Studies
  • Cardiovascular Research - Epidemiology
  • Cardiovascular Research - Hypertension
  • Diabetes - Cardiovascular Disease
  • Cardiovascular Research - Immunity and Atherosclerosis
  • ISSN: 1524-4636
E-mail: jan [dot] nilsson [at] med [dot] lu [dot] se

Lund University Diabetes Centre, CRC, SUS Malmö, Jan Waldenströms gata 35, House 91:12. SE-214 28 Malmö. Telephone: +46 40 39 10 00