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Two Rare Variants Explain Association with Acute Myocardial Infarction in an Extended Genomic Region Including the Apolipoprotein(A) Gene
Author(s) -
Koch Werner,
Mueller Jakob C.,
Schrempf Matthias,
Wolferstetter Hannah,
Kirchhofer Johannes,
Schömig Albert,
Kastrati Adnan
Publication year - 2013
Publication title -
annals of human genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.537
H-Index - 77
eISSN - 1469-1809
pISSN - 0003-4800
DOI - 10.1111/j.1469-1809.2012.00739.x
Subject(s) - haplotype , apolipoprotein b , genetics , genotype , biology , allele , myocardial infarction , single nucleotide polymorphism , confounding , medicine , gene , endocrinology , cholesterol
Summary 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.