Genetic variants in ABO blood group region, plasma soluble E-selectin levels and risk of type 2 diabetes.
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 approximately 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 x 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.
Qi
Lu
L
Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA. nhlqi@channing.harvard.edu
Cornelis
Marilyn C
MC
Kraft
Peter
P
Jensen
Majken
M
van Dam
Rob M
RM
Sun
Qi
Q
Girman
Cynthia J
CJ
Laurie
Cathy C
CC
Mirel
Daniel B
DB
Hunter
David J
DJ
Rimm
Eric
E
Hu
Frank B
FB
D000017:ABO Blood-Group System / Q000235:genetics*; D000328:Adult; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D019040:E-Selectin / Q000097:blood*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D015810:Linkage Disequilibrium; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors; D014481:United States
D000017:ABO Blood-Group System; D019040:E-Selectin; C546936:SELE protein, human