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 B. 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 journalArticlepeer-review

8 Scopus citations

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 - Apr 2015

Bibliographical note

Funding Information:
The authors thank the other investigators, the staff, and the participants of the MESA study for their valuable contributions. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org . MESA is conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with MESA investigators. Support is provided by grants and contracts N01 HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169 and RR-024156. Funding for adhesion protein levels was provided by NHLBI by grant R01HL98077. NIH/NIEHS P50 ES015915 “The Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air) is supported by the U.S. Environmental Protection Agency (EPA) under Science to Achieve Results (STAR) Program Grant # RD831697 and NIH/NIEHS P50 ES015915 award. Although the research described in this presentation has been funded wholly or in part by the United States Environmental Protection Agency through RD831697 to the University of Washington, it has not been subjected to the Agency’s required peer and policy review and, therefore, does not necessarily reflect the views of the Agency and no official endorsement should be inferred.” “The provision of genotyping data was supported in part by the National Center for Advancing Translational Sciences, CTSI grant UL1TR000124, and the National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC) grant DK063491 to the Southern California Diabetes Endocrinology Research Center”.

Publisher Copyright:
© 2015, Springer-Verlag Berlin Heidelberg.

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