Genetic and functional evidence links a missense variant in B4GALT1 to lower LDL and fibrinogen-Reference-Cited by-同舟云学术

Genetic and functional evidence links a missense variant in B4GALT1 to lower LDL and fibrinogen

Published:2021-12-03 Issue:6572 Volume:374 Page:1221-1227
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Montasser May E.¹^ORCID,Van Hout Cristopher V.²³^ORCID,Miloscio Lawrence²,Howard Alicia D.¹⁴^ORCID,Rosenberg Avraham⁵,Callaway Myrasol⁵,Shen Biao⁵^ORCID,Li Ning⁵^ORCID,Locke Adam E.²^ORCID,Verweij Niek²^ORCID,De Tanima²^ORCID,Ferreira Manuel A.²^ORCID,Lotta Luca A.²^ORCID,Baras Aris²,Daly Thomas J.⁵^ORCID,Hartford Suzanne A.⁵^ORCID,Lin Wei⁵^ORCID,Mao Yuan⁵,Ye Bin²^ORCID,White Derek⁵,Gong Guochun⁵^ORCID,Perry James A.¹^ORCID,Ryan Kathleen A.¹^ORCID,Fang Qing⁵,Tzoneva Gannie²^ORCID,Pefanis Evangelos⁵,Hunt Charleen⁵^ORCID,Tang Yajun⁵,Lee Lynn⁵^ORCID,Sztalryd-Woodle Carole¹⁶,Mitchell Braxton D.¹⁷^ORCID,Healy Matthew⁸^ORCID,Streeten Elizabeth A.¹⁹^ORCID,Taylor Simeon I.¹^ORCID,O’Connell Jeffrey R.¹,Economides Aris N.²⁵^ORCID,Della Gatta Giusy²^ORCID,Shuldiner Alan R.²^ORCID,

Affiliation:

1. Division of Endocrinology, Diabetes and Nutrition and Program for Personalized and Genomic Medicine, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA.

2. Regeneron Genetics Center, LLC, Tarrytown, NY 10591, USA.

3. Laboratorio Internacional de Investigatión sobre el Genoma Humano, Campus Juriquilla de la Universidad Nacional Autónoma de México, Querétaro, Querétaro 76230, México.

4. Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD 20993, USA.

5. Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.

6. US Department of Veterans Affairs, Washington, DC 20420 USA.

7. Geriatrics Research and Education Clinical Center, VA Medical Center, Baltimore, MD 21201, USA.

8. Enveda Biosciences, Boulder, CO 80301, USA.

9. Division of Genetics, Department of Pediatrics, University of Maryland School of Medicine, Baltimore, MD 21201, USA.

Abstract

Rare variants and blood LDL cholesterol A current goal in genomics is to identify genetic variation associated with actionable traits of clinical concern. Through exome sequencing of an Old Order Amish population, Montasser et al . identified a genetic variant that results in an amino acid change in the beta-1,4-galactosyltransferase 1 protein and is correlated with lower levels of cardiovascular disease. Investigation of the mutant protein showed that it affects genes associated with low-density lipoprotein cholesterol (LDL-C), and mice engineered to express the mutant protein exhibited a 38% decrease in blood LDL-C levels. This study suggests that such genomic sequencing and analysis can link genotype to phenotype and identify potentially clinically actionable pathways to treat disease. —LMZ

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference74 articles.

1. Heart Disease and Stroke Statistics—2018 Update: A Report From the American Heart Association

2. Hyperlipidemia as a Risk Factor for Cardiovascular Disease

3. Fibrinogen and cardiovascular disease.

4. Fibrin(ogen) in human disease: both friend and foe

5. Whole-Exome Sequencing Identifies Rare and Low-Frequency Coding Variants Associated with LDL Cholesterol

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