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

2010; Oxford University Press; Volume: 19; Issue: 9 Linguagem: Inglês

10.1093/hmg/ddq057

1460-2083

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

Cancer-related molecular mechanisms research

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 × 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.