Genetic variants in ABO blood group region, plasma soluble E-selectin levels and risk of type 2 diabetes

Lu Qi*, Marilyn C. Cornelis, Peter Kraft, Majken Jensen, Rob M. van Dam, Qi Sun, Cynthia J. Girman, Cathy C. Laurie, Daniel B. Mirel, David J. Hunter, Eric Rimm, Frank B. Hu

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

120 Scopus citations

Abstract

Blood soluble E-selectin (sE-selectin) levels have been related to various conditions such as type 2 diabetes. We performed a genome-wide association study among women of European ancestry from the Nurses' Health Study, and identified genome-wide significant associations between a cluster of markers at the ABO locus (9q34) and plasma sE-selectin concentration. The strongest association was with rs651007, which explained ~9.71% of the variation in sE-selectin concentrations. SNP rs651007 was also nominally associated with soluble intracellular cell adhesion molecule-1 (sICAM-1) (P = 0.026) and TNF-R2 levels (P = 0.018), independent of sE-selectin. In addition, the genetic-inferred ABO blood group genotypes were associated with sE-selectin concentrations (P = 3.55 3 10-47). Moreover, we found that the genetic-inferred blood group B was associated with a decreased risk (OR = 0.44, 0.27-0.70) of type 2 diabetes compared with blood group O, adjusting for sE-selectin, sICAM-1, TNF-R2 and other covariates. Our findings indicate that the genetic variants at ABO locus affect plasma sE-selectin levels and diabetes risk. The genetic associations with diabetes risk were independent of sE-selectin levels.

Original languageEnglish (US)
Article numberddq057
Pages (from-to)1856-1862
Number of pages7
JournalHuman molecular genetics
Volume19
Issue number9
DOIs
StatePublished - Feb 10 2010

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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