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

被引：139

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

来源：

HUMAN MOLECULAR GENETICS | 2010年 / 19卷 / 09期

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

页码：1856 / 1862

页数：7

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