Two rare variants explain association with acute myocardial infarction in an extended genomic region including the apolipoprotein(A) gene.

Koch, Werner; Mueller, Jakob C; Schrempf, Matthias; Wolferstetter, Hannah; Kirchhofer, Johannes; Schömig, Albert; Kastrati, Adnan

doi:10.1111/j.1469-1809.2012.00739.x

2013

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Titel:: Two rare variants explain association with acute myocardial infarction in an extended genomic region including the apolipoprotein(A) gene.
Dokumenttyp:: Journal Article; Research Support, Non-U.S. Gov't
Autor(en):: Koch, Werner; Mueller, Jakob C; Schrempf, Matthias; Wolferstetter, Hannah; Kirchhofer, Johannes; Schömig, Albert; Kastrati, Adnan
Abstract:: Relatively low numbers of kringle 4 type 2 repeats in apolipoprotein(a) and specific haplotypes of the SLC22A3-LPAL2-LPA region on chromosome 6 are associated with an increased risk of coronary disease. We examined the possibility that rs3798220 and rs10455872, short variations located in LPA [the apolipoprotein(a) gene], and related to the number of kringle 4 type 2 repeats, may serve as markers for the association between haplotypes and acute myocardial infarction. Genotypes were determined with TaqMan assays in a sample of 2136 cases and 1211 controls. The minor alleles of rs3798220 and rs10455872 were associated with increased risks (rs3798220-C: adjusted OR 2.14, 95% CI, 1.37-3.33, P = 0.00080; rs10455872-G: adjusted OR 1.74, 95% CI 1.36-2.24, P < 0.00001). After adjustments were made for potential confounders, none of nine polymorphisms included in a haplotype analysis were singly related to disease. Two risk haplotypes were identified; one (CCTTGTGTG; OR 1.25, 95% CI 1.08-1.45, P = 0.0022) was correlated with rs3798220-C and the other (CCCTGGATC; OR 1.65, 95% CI 1.14-2.38, P = 0.0074) with rs10455872-G. Thus, the findings allowed for a more precise definition of risk-associated markers: specific nucleotides in LPA instead of standard haplotypes defined by noneffective variants from the extensive SLC22A3-LPAL2-LPA region.
Zeitschriftentitel:: Ann Hum Genet
Jahr:: 2013
Band / Volume:: 77
Heft / Issue:: 1
Seitenangaben Beitrag:: 47-55
Sprache:: eng
Volltext / DOI:: doi:10.1111/j.1469-1809.2012.00739.x
PubMed:: http://view.ncbi.nlm.nih.gov/pubmed/23278389
Print-ISSN:: 0003-4800
TUM Einrichtung:: Klinik für Herz- und Kreislauferkrankungen im Erwachsenenalter (Prof. Schunkert); Urologische Klinik und Poliklinik
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