Genome-wide linkage analysis for identifying quantitative trait loci involved in the regulation of lipoprotein a (Lpa) levels

Sonia López, Alfonso Buil, Jordi Ordoñez, Juan Carlos Souto, Laura Almasy, Mark Lathrop, John Blangero, Francisco Blanco-Vaca, Jordi Fontcuberta, José Manuel Soria

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Lipoprotein Lp(a) levels are highly heritable and are associated with cardiovascular risk. We performed a genome-wide linkage analysis to delineate the genomic regions that influence the concentration of Lp(a) in families from the Genetic Analysis of Idiopathic Thrombophilia (GAIT) Project. Lp(a) levels were measured in 387 individuals belonging to 21 extended Spanish families. A total of 485 DNA microsatellite markers were genotyped to provide a 7.1cM genetic map. The variance component linkage method was used to evaluate linkage and to detect quantitative trait loci (QTLs). The main QTL that showed strong evidence of linkage with Lp(a) levels was located at the structural gene for apo(a) on chromosome 6 (LOD score=13.8). Interestingly, another QTL influencing Lp(a) concentration was located on chromosome 2 with an LOD score of 2.01. This region contains several candidate genes. One of them is the tissue factor pathway inhibitor (TFPI), which has antithrombotic action and also has the ability to bind lipoproteins. However, quantitative trait association analyses performed with 12 SNPs in TFPI gene revealed no association with Lp(a) levels. Our study confirms previous results on the genetic basis of Lp(a) levels. In addition, we report a new QTL on chromosome 2 involved in the quantitative variation of Lp(a). These data should serve as the basis for further detection of candidate genes and to elucidate the relationship between the concentration of Lp(a) and cardiovascular risk.

Original languageEnglish (US)
Pages (from-to)1372-1379
Number of pages8
JournalEuropean Journal of Human Genetics
Volume16
Issue number11
DOIs
StatePublished - 2008
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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