The LPA gene encodes a plasminogene-like lipoprotein, Lp(a), which is bound to apolipoprotein B. Height plasma concentrations of that lipoprotein are associated with accelerated cardiovascular disease. Genetically, plasma concentration of Lp(a) is associated with the number of kringle IV-2 repeats such that shorter proteins result higher Lp(a) levels. An association is also found between the number of kringles and two polymorphisms (rs10455872 and rs3798220).
The LPA gene and the plasminogen gene (PLG) show great sequence homology. Both genes are located in a head-to-head position on chromosome 6 (6q26). It is hypothesized that the LPA gene arose from the PLG gene by duplication and subsequent deletion and copy number variation. However, as calculations of the time of divergence yield different results when calculated for the 3'UTR (PLG distant region) and 5'UTR (PLG-near region), 40 and 7 million years, respectively, the LPA gene may have evolved in two steps.
While the domain structure of the PLG gene consists of signal peptide, tail, kringles 1-5, and protease, the LPA gene lacks the tail and kringles 1-3. In addition it has a variable number of kringle 4 (10-51). 10 types of kringle 4 showing subtle sequnece differences can be distinguished. Only with kringle 4-2 copy number variations (1-42 are observed). Kringle 4-2 consists of two exons (161 bp and 181 bp), an intra-kringle intron between these exons of about 4kb, and an inter-kringle intron to the next kringle (1.2kb).
The protease of the LPA gene significantly differs from that of plasminogen, so it is not clear whether it acts as a protease at all.
The minor allele frequency of the two SNPs (rs10455872 and rs3798220) is 7% and 2%, respectively. 15% of the normal population carries at least one such minor allele. Among carriers of the large lipoprotein (a) [Lp(a)] phenotype only 2% carry one of the two minoralleles while among patient with the short phenotype the percentage is 53%.
Clinic | Method | Carrier testing |
Turnaround | 5 days | |
Specimen type | genomic DNA |
Clinic | Method | Massive parallel sequencing |
Turnaround | 25 days | |
Specimen type | genomic DNA |
Clinic | Method | Genomic sequencing of the entire coding region |
Turnaround | 25 days | |
Specimen type | genomic DNA |
Clinic | Method | Target mutation analysis |
Turnaround | 25 days | |
Specimen type | genomic DNA |
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