Genetic and functional evidence relates a missense variant inB4GALT1to lower LDL-C and fibrinogen

crossref(2019)

引用 0|浏览0
暂无评分
摘要
AbstractIncreased LDL-cholesterol (LDL-C) and fibrinogen are independent risk factors for cardiovascular disease (CVD). We identified novel associations between an Amish-enriched missense variant (p.Asn352Ser) in a functional domain of beta-1,4-galactosyltransferase 1 (B4GALT1) and 13.5 mg/dl lower LDL-C (p=1.6E-15), and 26 mg/dl lower plasma fibrinogen (p= 9.8E-05). N-linked glycan profiling found p.Asn352Ser to be associated (p-values from 1.4E-06 to 1.0E-17) with decreased glycosylation of glycoproteins including: fibrinogen, ApoB100, immunoglobulin G (IgG), and transferrin.In vitroassays found that the mutant (352Ser) protein had 50% lower galactosyltransferase activity compared to wild type (352Asn) protein. Knockdown ofb4galt1in zebrafish embryos resulted in significantly lower LDL-C compared to control, which was fully rescued by co-expression of 352Asn humanB4GALT1mRNA but only partially rescued by co-expression of 352Ser humanB4GALT1mRNA. Our findings establishB4GALT1as a novel gene associated with lower LDL-C and fibrinogen and suggest that targeted modulation of protein glycosylation may represent a therapeutic approach to decrease CVD risk.
更多
查看译文
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要