A common Hpa I RFLP of apolipoprotein C-I increases gene transcription and exhibits an ethnically distinct pattern of linkage disequilibrium with the alleles of apolipoprotein E

Abstract

Apolipoprotein (apo) C-I is a constituent of triglyceride-rich lipoproteins (TGRL) that interferes with their hepatic clearance. Functional polymorphism in the apoC-I gene has not been established. We determined that an Hpa I site variably present at ؊ 317 relative to the apoC-I gene is produced by a 4-bp CGTT insertion. The apoC-I Hpa I alleles showed an ethnically distinct pattern of linkage disequilibrium with the alleles of the adjacent apoE gene. The frequency of apoC-I Hpa I-positive (H2) with apoE 2 was 0.98, without significant ethnic difference. In contrast, the frequency of H2 with apoE 4 was 0.85 in European-Americans but only 0.55 in African-Americans ( P Ͻ 0.001). The frequency of H2 with apoE 3 was 0.02 in European-Americans and 0.08 in African-Americans ( P Ͻ 0.001). African-American apoE 3/ 3 carriers of apoC-I H2 had 19% lower fasting triglyceride levels than H1 homozygotes ( P ‫؍‬ 0.03) along with 18% higher HDL-cholesterol levels ( P ‫؍‬ 0.02). ApoB levels were 21% lower ( P ‫؍‬ 0.002). H2-allelic reporter-gene constructions showed 50% higher expression in transient transfection studies. We localized the source of this difference in expression to the CGTT insertion itself. Deletion studies of the H1 allele showed a negative transcriptional effect of the polymorphic region. An H1 oligodeoxynucleotide showed specific binding of a hepatomacell nuclear protein not evident with an H2 oligodeoxynucleotide. The H2 sequence may decrease the binding of a negatively acting transcription factor, leading to overexpression of apoC-I. This may produce a functional effect on lipoprotein levels but confirmation is needed in other populations. -Xu, Y.

Association of Apolipoproteins E4 and C1 With Onset Age and Memory: A Study of Sporadic Alzheimer Disease in Taiwan

“…8,12,13 Linkage disequilibrium between the ApoE alleles and the HpaI alleles of APOC1 was observed in European Americans and Dutch population, but it was less stronger in African Americans. 14 However, in the AD and age-associated memory impairment groups, ApoE e4 and APOC1 A allele are strongly associated. 2,3,15 The frequency of the APOC1 A allele in the controls in this study is in line with the previous reports, but there is some ethnic variation.…”

Secretome-Derived Isotope Tags (SDIT) Reveal Adipocyte-Derived Apolipoprotein C-I as a Predictive Marker for Cardiovascular Disease

“…Little is known about the function and regulation of apoC-I or its contribution to dietary fat metabolism and clinical dyslipidemia in humans. Polymorphism analysis of apoC-I in humans revealed a polymorphism in the promoter region of apoC-I. , Interestingly, ApoE and apoC-I polymorphisms are associated with the genotype related to the CVD phenotype in African Americans . ApoC-I genotypes showed an ethnically distinct phenotype relationship with regard to coronary artery disease (CAD) and CAD risk factors .…”

APOE and APOC1 Promoter Polymorphisms and the Risk of Alzheimer Disease in African American and Caribbean Hispanic Individuals

“…The HpaI variant in APOC1 was genotyped as previously described. 32 The accuracy of genotyping was greater than 97% for each marker, as indicated by redetermining the genotypes in 150 to 250 subjects.…”