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

被引:138
作者
Qi, Lu [1 ,3 ,4 ]
Cornelis, Marilyn C. [1 ]
Kraft, Peter [3 ,4 ]
Jensen, Majken [1 ]
van Dam, Rob M. [1 ,2 ,3 ,4 ]
Sun, Qi [1 ]
Girman, Cynthia J. [5 ]
Laurie, Cathy C. [6 ]
Mirel, Daniel B. [7 ,8 ]
Hunter, David J. [2 ,3 ,4 ]
Rimm, Eric [1 ,2 ,3 ,4 ]
Hu, Frank B. [1 ,2 ,3 ,4 ]
机构
[1] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA
[2] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA
[3] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA
[4] Harvard Univ, Sch Med, Boston, MA USA
[5] Merck Res Labs, Dept Epidemiol, N Wales, PA 19454 USA
[6] Univ Washington, Dept Biostat, Seattle, WA 98195 USA
[7] MIT, Broad Inst, Ctr Genotyping & Anal, Cambridge, MA 02142 USA
[8] Harvard Univ, Cambridge, MA 02142 USA
关键词
GENOME-WIDE ASSOCIATION; CORONARY-HEART-DISEASE; ADHESION MOLECULES; ENDOTHELIAL DYSFUNCTION; INFLAMMATORY MARKERS; WOMEN; POPULATION; MELLITUS; LOCI; HYPERTENSION;
D O I
10.1093/hmg/ddq057
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 similar to 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.
引用
收藏
页码:1856 / 1862
页数:7
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