The I4399M variant of apolipoprotein(a) is associated with increased oxidized phospholipids on apolipoprotein B-100 particles.
OBJECTIVE
The LPA I4399M (rs3798220) single nucleotide polymorphism (SNP) is associated with increased plasma levels of Lp(a) and advanced coronary artery disease (CAD). We hypothesized that carriers of the Met allele of the I4399M SNP would also have elevated levels of oxidized phospholipids (OxPL) on apoB (OxPL/apoB) particles.


RESULTS
Plasma levels of Lp(a) and OxPL/apoB were measured in non-carriers (TT genotype, n=116) and carriers (CT/CC genotype, n=58) of the I4399M SNP. Carriers had significantly higher Lp(a) levels [median (interquartile range, IQR)] [43 (9-57)mg/dl vs. 5.5 (2-20)mg/dl, p<0.0001] and smaller apolipoprotein(a) isoforms than non-carriers (number of kringle IV repeats: 18(17-20) vs. 22(18-25), p=0.002). Median (IQR) OxPL/apoB levels were significantly higher in carriers than non-carriers [8019 (6254-31,785) relative light units (RLU) vs. 2168 (1303-5869), p<0.0001]. Patients with small apolipoprotein(a) isoforms had the highest OxPL/apoB levels. The number of kringle IV repeats was inversely related to Lp(a) (r=-0.43, p<0.001) and OxPL/apoB (r=-0.36, p<0.0001) levels.


CONCLUSIONS
The CT and CC genotypes of the I4399M SNP in the LPA gene are associated with elevated OxPL/apoB levels, which primarily represent OxPL on Lp(a). The concomitant increase of OxPL/apoB levels in the setting of small apolipoprotein(a) isoforms may potentiate the atherogenic effect on CAD of elevated Lp(a) levels in carriers of the I4399M SNP.
Arai
Kiyohito
K
Department of Medicine, University of California San Diego, La Jolla, CA 92093-0682, United States.
Luke
May M
MM
Koschinsky
Marlys L
ML
Miller
Elizabeth R
ER
Pullinger
Clive R
CR
Witztum
Joseph L
JL
Kane
John P
JP
Tsimikas
Sotirios
S
D053299:Apolipoprotein B-100 / Q000097:blood*; D001054:Apolipoproteins A / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000209:etiology / Q000235:genetics; D005260:Female; D006579:Heterozygote; D006801:Humans; D017270:Lipoprotein(a) / Q000097:blood; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D010743:Phospholipids / Q000097:blood*; D020641:Polymorphism, Single Nucleotide
D053299:Apolipoprotein B-100; D001054:Apolipoproteins A; D017270:Lipoprotein(a); D010743:Phospholipids