A functional polymorphism of apolipoprotein C1 detected by mass spectrometry

Abstract

A survey of plasma proteins in approximately 1300 individuals by MALDI‐TOF MS resulted in identification of a structural polymorphism of apolipoprotein C1 (ApoC1) that was found only in persons of American Indian or Mexican ancestry. MS/MS analysis revealed that the alteration consisted of a T45S variation. The methyl group of T45 forms part of the lipid‐interacting surface of ApoC1. In agreement with an impact on lipid contact, the S45 variant was more susceptible to N‐terminal truncation by dipeptidylpeptidase IV in vitro than was the T45 variant. The S45 protein also displayed greater N‐terminal truncation (loss of Thr‐Pro) in vivo than the T45 variant. The S45 variant also showed preferential distribution to the very‐low‐density lipoprotein fraction than the T45 protein. These properties indicate a functional effect of the S45 variant and support a role for residue 45 in lipid contact and lipid specificity. Further studies are needed to determine the effects of the variant and its altered N‐terminal truncation on the metabolic functions of ApoC1.

WITHDRAWN: Extraordinary apolipoprotein oxidation in chronic hepatitis C and liver cirrhosis

“…Indians and persons of Mexican ancestry that is linked to obesity and diabetes (14,15). It has revealed a unique and consistent pattern of protein ratios in each healthy person (13) and has detected some rather extreme proteome changes in a subset of healthy volunteers who received low dose endotoxin (11).…”

Apolipoprotein C-1 maintains cell survival by preventing from apoptosis in pancreatic cancer cells

“…We obtained two sequences, which were identical except for two additional amino acids on the N terminus. ApoC-1 is known to have molecular sizes of 6630 and 6420 Da (Wroblewski et al, 2006), which may represent these two amino-acids truncation. The immunodepletion assay confirmed that these peaks were ApoC-1; the reaction of serum with control mouse immunoglobulin G (IgG) did not affect the 6630 and 6420 Da peaks of the ProteinChip array, whereas both peaks were clearly decreased when the anti-ApoC-1 antibody was used (Figure 1d).…”

APOC1 T45S polymorphism is associated with reduced obesity indices and lower plasma concentrations of leptin and apolipoprotein C-I in aboriginal Canadians

“…Therefore, our study suggests that the S45 variant in the Canadian First Nations results in lower concentrations of apo C-I and leptin, which may lead to lower percent body fat and waist circumference. However, a previous study has suggested the S45 variant to have greater N-terminal truncation and preferential distribution to the VLDL fraction compared with the APOC1 T45 variant ( 47 ); increased concentration of apo C-I was recently observed to be associated with decreased visceral fat in men with MetS ( 48 ).…”