SELP and SELPLG genetic variation is associated with cell surface measures of SELP and SELPLG: the Atherosclerosis Risk in Communities Carotid MRI Study.
BACKGROUND
P-selectin (SELP) and its ligand, P-selectin glycoprotein ligand 1 (SELPLG), play key roles in both the inflammatory response and the atherosclerotic process. Previous studies have shown genetic variation in the SELP gene [selectin P (granule membrane protein 140 kDa, antigen CD62)] to be associated with plasma SELP concentrations; however, the major biological function of SELP (and SELPLG) is at the cell surface. We therefore investigated the association of SELP polymorphisms with platelet SELP measures and polymorphisms in the SELPLG gene (selectin P ligand) with lymphocyte, granulocyte, and monocyte SELPLG measures among 1870 participants in the Atherosclerosis Risk in Communities (ARIC) Carotid MRI Study.


METHODS
Whole-blood flow cytometry was used to analyze leukocyte and platelet markers in the ARIC Carotid MRI Study. The allele frequencies for the SELP and SELPLG polymorphisms of whites and African Americans were markedly different; therefore, all analyses were race specific.


RESULTS
SELP T715P was significantly associated with lower values for platelet SELP measures in whites (P = 0.0001), whereas SELP N562D was significantly associated with higher values for SELP measures in African Americans (P = 0.02). SELPLG M62I was significantly associated with lower granulocyte and monocyte SELPLG measures in African Americans (P = 0.003 and P = 0.0002, respectively) and with lower lymphocyte SELPLG measures in whites (P = 0.01).


CONCLUSIONS
Specific SELP and SELPLG polymorphisms were associated with cell surface measures of SELP and SELPLG in both whites and African Americans in the ARIC Carotid MRI Study. To our knowledge, this study is the first to examine the association of SELP and SELPLG genetic variation with measures of cell surface SELP and SELPLG.
Volcik
Kelly A
KA
Human Genetics Center, University of Texas Health Science Center School of Public Health, Houston, TX 77030, USA. Kelly.A.Volcik@uth.tmc.edu
Catellier
Diane
D
Folsom
Aaron R
AR
Matijevic
Nena
N
Wasserman
Bruce
B
Boerwinkle
Eric
E
D050197:Atherosclerosis / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D044383:Black People; D002339:Carotid Arteries / Q000473:pathology*; D005434:Flow Cytometry; D006801:Humans; D008279:Magnetic Resonance Imaging; D008562:Membrane Glycoproteins / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors; D051149:Selenoprotein P / Q000235:genetics*; D044465:White People; D001741:Black or African American
D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein; D051149:Selenoprotein P