| First Author | Montasser ME | Year | 2021 |
| Journal | Science | Volume | 374 |
| Issue | 6572 | Pages | 1221-1227 |
| PubMed ID | 34855475 | Mgi Jnum | J:317226 |
| Mgi Id | MGI:6834010 | Doi | 10.1126/science.abe0348 |
| Citation | Montasser ME, et al. (2021) Genetic and functional evidence links a missense variant in B4GALT1 to lower LDL and fibrinogen. Science 374(6572):1221-1227 |
| abstractText | Increased blood levels of low-density lipoprotein cholesterol (LDL-C) and fibrinogen are independent risk factors for cardiovascular disease. We identified associations between an Amish-enriched missense variant (p.Asn352Ser) in a functional domain of beta-1,4-galactosyltransferase 1 (B4GALT1) and 13.9 milligrams per deciliter lower LDL-C (P = 4.1 ���� 10������19) and 29 milligrams per deciliter lower plasma fibrinogen (P = 1.3 ���� 10������5). B4GALT1 gene������based analysis in 544,955 subjects showed an association with decreased coronary artery disease (odds ratio = 0.64, P = 0.006). The mutant protein had 50% lower galactosyltransferase activity compared with the wild-type protein. N-linked glycan profiling of human serum found serine 352 allele to be associated with decreased galactosylation and sialylation of apolipoprotein B100, fibrinogen, immunoglobulin G, and transferrin. B4galt1 353Ser knock-in mice showed decreases in LDL-C and fibrinogen. Our findings suggest that targeted modulation of protein galactosylation may represent a therapeutic approach to decreasing cardiovascular disease. |
