Clinical and genetic correlates of soluble P‐selectin in the community

Lee, Douglas S.; Larson, Martin G.; Lunetta, Kathryn L.; Dupuis, Josée; Rong, Jian; Keaney, John F.; Lipinska, Izabella; Baldwin, Clinton T.; Vasan, Ramachandran S.; Benjamin, Emelia J.

doi:10.1111/j.1538-7836.2007.02805.x

Cited by 32 publications

(45 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[3][4][5][6] In the combined Framingham Offspring (EA) and Omni minority cohorts, 5 the proportion of interindividual variability in soluble P-selectin explained by clinical factors was 10%, similar to the 13% explained among CARDIA participants. Circulating P-selectin concentration has been reported to be lower in individuals of African origin relative to Europeans and South Asians living in England.…”

Section: Discussionmentioning

confidence: 96%

“…6 In the Framingham and Omni cohorts, soluble P-selectin was higher among ethnic minority participants (comprised of African-, Hispanic-and Asian-Americans) than among EA participants. 5 In CARDIA, self-reported ethnicity was not strongly correlated with soluble P-selectin. Regional environmental or genetic factors, including recent admixture, might account for some of the discrepant findings among studies.…”

Section: Discussionmentioning

confidence: 99%

“…4,5,11 The Thr715Pro polymorphism (rs6136) of the P-selectin gene (SELP) has been associated with lower soluble P-selectin levels, accounting for Ϸ10% to 20% of the variation in healthy EuropeanAmerican (EA) populations. [12][13][14][15][16] Other SELP polymorphisms, including Val599Leu (rs6133), appear to account for some of the residual variance in soluble P-selectin among EAs.…”

Section: Conclusion-commonmentioning

confidence: 99%

“…[12][13][14][15][16] Other SELP polymorphisms, including Val599Leu (rs6133), appear to account for some of the residual variance in soluble P-selectin among EAs. 5,12,16 The Thr715Pro polymorphism is rare in people of African descent, 14,15 but little is known about determinants of soluble P-selectin among African-Americans (AA) or allelic heterogeneity of other SELP polymorphisms between population groups.Using data from a large well-characterized population of young EA and AA adults recruited as part of the longitudinal Coronary Artery Risk Development in Young Adults (CARDIA)Original …”

mentioning

confidence: 99%

“…Increased soluble P-selectin levels are associated with various cardiovascular risk factors and occurrence or severity of acute and chronic cardiovascular disorders, primarily among older adults. [1][2][3][4][5][6] In some 7 but not all 8 cohorts of apparently healthy individuals, higher soluble P-selectin levels predicted future clinical cardiovascular events. Cross-sectional studies suggest soluble 9 or platelet 10 P-selectin is significantly correlated with subclinical atherosclerosis, even after accounting for known risk factors.…”

mentioning

confidence: 99%

See 4 more Smart Citations

Soluble P-Selectin, SELP Polymorphisms, and Atherosclerotic Risk in European-American and African-African Young Adults

Reiner

Carlson

Thyagarajan

et al. 2008

ATVB

View full text Add to dashboard Cite

Objective-To characterize the genetic and clinical correlates of soluble P-selectin, and the relationship of P-selectin to atherosclerotic risk, in young European-American (EA) and African-American (AA) adults. Methods and Results-We assessed the interrelationships between 25 common SELP polymorphisms, soluble P-selectin, and atherosclerotic risk in 1222 EA and 1072 AA from the longitudinal population-based CARDIA study. Male sex, smoking, blood pressure, and metabolic status were strong cross-sectional correlates of soluble P-selectin among CARDIA subjects aged 33 to 45 years, explaining 13% of the variance. Among EAs, higher soluble P-selectin predicted carotid intima-media thickness (IMT) measured 5 years later, even after accounting for traditional risk factors. Common SELP nucleotide sequence variants explained 11% and 5% of the interindividual variation in soluble P-selectin levels in EAs and AAs, respectively. Four distinct variants contributed to P-selectin phenotype in EAs, including a polymorphism of the 5Ј SELP haplotype block associated with carotid IMT. Half of the phenotypic variation attributable to SELP in EAs could be explained by the Thr715Pro polymorphism, whereas Val599Leu was more strongly associated with soluble P-selectin among AAs. Key Words: P-selectin Ⅲ carotid atherosclerosis Ⅲ haplotype P -selectin (CD62P) is a cell adhesion receptor expressed mainly at the surface of platelets and endothelial cells and plays an important role in the early stages of atherosclerosis. 1 A soluble form of P-selectin lacking the transmembrane domain circulates in plasma. Increased soluble P-selectin levels are associated with various cardiovascular risk factors and occurrence or severity of acute and chronic cardiovascular disorders, primarily among older adults. [1][2][3][4][5][6] In some 7 but not all 8 cohorts of apparently healthy individuals, higher soluble P-selectin levels predicted future clinical cardiovascular events. Cross-sectional studies suggest soluble 9 or platelet 10 P-selectin is significantly correlated with subclinical atherosclerosis, even after accounting for known risk factors. Prospective data on soluble P-selectin as a predictor of early atherosclerotic disease, however, have not been previously reported. Conclusions-CommonThe heritability of circulating P-selectin levels has been estimated between 45% and 70%. 4,5,11 The Thr715Pro polymorphism (rs6136) of the P-selectin gene (SELP) has been associated with lower soluble P-selectin levels, accounting for Ϸ10% to 20% of the variation in healthy EuropeanAmerican (EA) populations. [12][13][14][15][16] Other SELP polymorphisms, including Val599Leu (rs6133), appear to account for some of the residual variance in soluble P-selectin among EAs. 5,12,16 The Thr715Pro polymorphism is rare in people of African descent, 14,15 but little is known about determinants of soluble P-selectin among African-Americans (AA) or allelic heterogeneity of other SELP polymorphisms between population groups.Using data from a large well-characterized populati...

show abstract

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Conclusion-commonmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Soluble P-Selectin, SELP Polymorphisms, and Atherosclerotic Risk in European-American and African-African Young Adults

Reiner

Carlson

Thyagarajan

et al. 2008

ATVB

View full text Add to dashboard Cite

show abstract

Increased Soluble VCAM-1 and Normal P-Selectin in Cystic Fibrosis: a Cross-Sectional Study

Nowak

Wojsyk‐Banaszak

Mądry

et al. 2017

Lung

View full text Add to dashboard Cite

PurposeAs life expectancy in cystic fibrosis (CF) increases, questions regarding its potential impact on cardiovascular health arise. Soluble vascular cell adhesion molecule 1 (sVCAM-1), P-selectin (sP-selectin) are proposed as biomarkers of cardiovascular disease. We aimed to: compare their concentrations in clinically stable CF patients and healthy subjects (HS) and verify whether they independently correlate with CF characteristics.MethodsSerum sVCAM-1 and sP-selectin levels were measured using ELISA. CF was characterized using: forced expiratory volume in 1 s, exocrine pancreatic and CF-related liver disease status, Pseudomonas aeruginosa colonization, serum high-sensitivity C-reactive protein, and body mass index (BMI). CFTR genotypes were classified as severe (classes I and II) or other.Results108 CF patients and 51 healthy subjects volunteered for the study. In the CF group BMI was lower (median [IQR]: 20.5 kg/m2 [18.4–22.2] vs. 21.6 kg/m2 [19.9–23.4], p = 0.02) and hsCRP levels were higher (3.6 mg/L [1.1–7.1] vs. 0.5 mg/dL [0.3–1.0], p < 10−10). While sVCAM-1 concentrations were greater in CF patients (1018 ng/mL [851–1279] vs. 861 ng/mL [806–979], p < 10−4), sP-selectin levels did not differ (155 ng/mL [129–188] vs. 156 ng/mL [144–177], p = 0.48). None of the multivariable regression models was valid for the prediction of sVCAM-1 and sP-selectin in CF.ConclusionsWe found higher sVCAM-1 concentrations in CF patients than in healthy subjects, which were not explained by CF characteristics. Further research is required to check whether sVCAM-1 is a marker of microangiopathy in CF.

show abstract

Multi-ethnic analysis reveals soluble l-selectin may be post-transcriptionally regulated by 3′UTR polymorphism: the Multi-Ethnic Study of Atherosclerosis (MESA)

et al. 2015

View full text Add to dashboard Cite

L-selectin is constitutively expressed on leukocytes and mediates their interaction with endothelial cells during inflammation. Previous studies on the association of soluble L-selectin (sL-selectin) with cardiovascular disease (CVD) are inconsistent. Genetic variants associated with sL-selectin levels may be a better surrogate of levels over a lifetime. We explored the association of genetic variants and sL-selectin levels in a race/ethnicity stratified random sample of 2,403 participants in the Multi-Ethnic Study of Atherosclerosis (MESA). Through a genome-wide analysis with additive linear regression models, we found that rs12938 on the SELL gene accounted for a significant portion of the protein level variance across all four races/ethnicities. To evaluate potential additional associations, elastic net models were used for variants located in the SELL/SELP/SELE genetic region and an additional two SNPs, rs3917768 and rs4987361, were associated with sL-selectin levels in African Americans. These variants accounted for a portion of protein variance that ranged from 4% in Hispanic to 14% in African Americans. To investigate the relationship of these variants with CVD, 6,317 subjects were used. No significant association was found between any of the identified SNPs and carotid intima-media thickness or presence of carotid plaque using linear and logistic regression, respectively. Similarly no significant results were found for coronary artery calcium or coronary heart disease events. In conclusion, we found that variants within the SELL gene are associated with sL-selectin levels. Despite accounting for a significant portion of the protein level variance, none of the variants was associated with clinical or subclinical CVD.

show abstract

Clinical and genetic correlates of soluble P‐selectin in the community

Cited by 32 publications

References 65 publications

Soluble P-Selectin, SELP Polymorphisms, and Atherosclerotic Risk in European-American and African-African Young Adults

Soluble P-Selectin, SELP Polymorphisms, and Atherosclerotic Risk in European-American and African-African Young Adults

Increased Soluble VCAM-1 and Normal P-Selectin in Cystic Fibrosis: a Cross-Sectional Study

Multi-ethnic analysis reveals soluble l-selectin may be post-transcriptionally regulated by 3′UTR polymorphism: the Multi-Ethnic Study of Atherosclerosis (MESA)

Contact Info

Product

Resources

About