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

Cecilia Berardi, Nicholas Larson, Paul A. Decker, Christina L. Wassel, Phillip S. Kirsch, James S. Pankow, Michele M. Sale, Mariza De Andrade, Hugues Sicotte, Weihong Tang, Naomi Q. Hanson, Michael Y. Tsai, Yii Der Ida Chen, Suzette J Bielinski

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)393-403
Number of pages11
JournalHuman Genetics
Volume134
Issue number4
DOIs
StatePublished - 2015

Fingerprint

Selectins
Atherosclerosis
Linear Models
Cardiovascular Diseases
African Americans
Single Nucleotide Polymorphism
Carotid Intima-Media Thickness
Proteins
Hispanic Americans
Genes
Coronary Disease
Coronary Vessels
Leukocytes
Endothelial Cells
Logistic Models
Genome
Inflammation
Calcium

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Multi-ethnic analysis reveals soluble l-selectin may be post-transcriptionally regulated by 3′UTR polymorphism : the Multi-Ethnic Study of Atherosclerosis (MESA). / Berardi, Cecilia; Larson, Nicholas; Decker, Paul A.; Wassel, Christina L.; Kirsch, Phillip S.; Pankow, James S.; Sale, Michele M.; De Andrade, Mariza; Sicotte, Hugues; Tang, Weihong; Hanson, Naomi Q.; Tsai, Michael Y.; Chen, Yii Der Ida; Bielinski, Suzette J.

In: Human Genetics, Vol. 134, No. 4, 2015, p. 393-403.

Research output: Contribution to journalArticle

Berardi, Cecilia ; Larson, Nicholas ; Decker, Paul A. ; Wassel, Christina L. ; Kirsch, Phillip S. ; Pankow, James S. ; Sale, Michele M. ; De Andrade, Mariza ; Sicotte, Hugues ; Tang, Weihong ; Hanson, Naomi Q. ; Tsai, Michael Y. ; Chen, Yii Der Ida ; Bielinski, Suzette J. / Multi-ethnic analysis reveals soluble l-selectin may be post-transcriptionally regulated by 3′UTR polymorphism : the Multi-Ethnic Study of Atherosclerosis (MESA). In: Human Genetics. 2015 ; Vol. 134, No. 4. pp. 393-403.
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abstract = "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.",
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T1 - Multi-ethnic analysis reveals soluble l-selectin may be post-transcriptionally regulated by 3′UTR polymorphism

T2 - the Multi-Ethnic Study of Atherosclerosis (MESA)

AU - Berardi, Cecilia

AU - Larson, Nicholas

AU - Decker, Paul A.

AU - Wassel, Christina L.

AU - Kirsch, Phillip S.

AU - Pankow, James S.

AU - Sale, Michele M.

AU - De Andrade, Mariza

AU - Sicotte, Hugues

AU - Tang, Weihong

AU - Hanson, Naomi Q.

AU - Tsai, Michael Y.

AU - Chen, Yii Der Ida

AU - Bielinski, Suzette J

PY - 2015

Y1 - 2015

N2 - 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.

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