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The I4399M variant of apolipoprotein(a) is associated with increased oxidized phospholipids on apolipoprotein B-100 particles.
Atherosclerosis. 2010 Apr; 209(2):498-503.A

Abstract

OBJECTIVES

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.

METHODS AND 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.

CONCLUSION

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.

Authors+Show Affiliations

Department of Medicine, University of California San Diego, La Jolla, CA 92093-0682, United States.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19880117

Citation

Arai, Kiyohito, et al. "The I4399M Variant of Apolipoprotein(a) Is Associated With Increased Oxidized Phospholipids On Apolipoprotein B-100 Particles." Atherosclerosis, vol. 209, no. 2, 2010, pp. 498-503.
Arai K, Luke MM, Koschinsky ML, et al. The I4399M variant of apolipoprotein(a) is associated with increased oxidized phospholipids on apolipoprotein B-100 particles. Atherosclerosis. 2010;209(2):498-503.
Arai, K., Luke, M. M., Koschinsky, M. L., Miller, E. R., Pullinger, C. R., Witztum, J. L., Kane, J. P., & Tsimikas, S. (2010). The I4399M variant of apolipoprotein(a) is associated with increased oxidized phospholipids on apolipoprotein B-100 particles. Atherosclerosis, 209(2), 498-503. https://doi.org/10.1016/j.atherosclerosis.2009.09.077
Arai K, et al. The I4399M Variant of Apolipoprotein(a) Is Associated With Increased Oxidized Phospholipids On Apolipoprotein B-100 Particles. Atherosclerosis. 2010;209(2):498-503. PubMed PMID: 19880117.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The I4399M variant of apolipoprotein(a) is associated with increased oxidized phospholipids on apolipoprotein B-100 particles. AU - Arai,Kiyohito, AU - Luke,May M, AU - Koschinsky,Marlys L, AU - Miller,Elizabeth R, AU - Pullinger,Clive R, AU - Witztum,Joseph L, AU - Kane,John P, AU - Tsimikas,Sotirios, Y1 - 2009/10/12/ PY - 2009/08/27/received PY - 2009/09/17/revised PY - 2009/09/29/accepted PY - 2009/11/3/entrez PY - 2009/11/3/pubmed PY - 2010/6/15/medline SP - 498 EP - 503 JF - Atherosclerosis JO - Atherosclerosis VL - 209 IS - 2 N2 - OBJECTIVES: 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. METHODS AND 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. CONCLUSION: 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. SN - 1879-1484 UR - https://www.unboundmedicine.com/medline/citation/19880117/The_I4399M_variant_of_apolipoprotein_a__is_associated_with_increased_oxidized_phospholipids_on_apolipoprotein_B_100_particles_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0021-9150(09)00836-3 DB - PRIME DP - Unbound Medicine ER -