LPA-Intron 25 Genotype Test
LPA-Intron 25 genotyping helps predict risk of Coronary Heart Disease (CHD)1-3
Carriers of the LPA-Intron 25 gene variant have been shown to have an increased risk of CHD compared with noncarriers in studied populations.a The association of LPA-Intron 25 with CHD was reported to be independent of age, gender, and the LPA 4399Met genotype (LPA-Aspirin).1,8
What is LPA-Intron 25?
The LPA-Intron 25 polymorphismb is associated with risk of CHD. This polymorphism is an intron of the LPA gene, which encodes the apolipoprotein(a) component of the Lp(a) particle.
Risk Associated with the LPA-Intron 25 Genotype
Results from a meta-analysis of several studies:1
- LPA-Intron 25 carriers had a 1.47x increased risk of CHD compared to noncarriersc
- This risk was independent of traditional risk factors1,8
Potential Clinical Implications
- LPA-Intron 25 carriers may have increased risk of CHD. These test results may help health care providers take steps to characterize and reduce other risk factors that can contribute to the initiation or progression of heart disease.
- Lp(a) levels may vary depending on physiological status,4-7 so clinicians may choose to monitor this risk factor over time. LPA-Intron 25 is a one-time genetic test.
- Knowledge of LPA-Intron 25 carrier status and associated increased risk may also help health care providers increase patients' adherence to treatment recommendations.d
Patients who carry a LPA-Intron 25 risk variant will not invariably develop CHD. Similarly, patients who do not carry LPA-Intron 25 risk variants are not immune to developing CHD.
The LPA-Intron 25 Genotype Test was developed and its performance characteristics were determined by Berkeley HeartLab, a CLIA-certified and CAP-accredited laboratory. It has not been cleared or approved by the FDA.a. Study populations predominantly consisted of Caucasian men and women in Europe. LPA-Intron 25 associated-risk has not been studied in African American, Mexican American or East Asian populations. However, carrier frequencies in these ethnic groups are approximately 2% in African American and Mexican American populations, and ≤1% in East Asian populations.
b. The LPA-Intron 25 polymorphism is referred to as rs10455872 in research studies.
c. Compared with noncarriers, patients who carry one copy of the c allele are expected to have 1.47x increased risk, those who carry two copies of the c allele are expected to have about 2.2x increased risk (based on an additive model by Clarke et al1).
d. To date, there are no data to support increased medication compliance based on knowledge of LPA-Intron 25 carrier status.
References
- Clarke, R, et al. Genetic Variants Associated with Lp(a) Lipoprotein Level and Coronary Disease. N Engl J Med. 2009;361:2518-2528.
- Shiffman, D, et al. Single Variants can Explain the Association Between Coronary Heart Disease and Haplotypes in the Apolipoprotein(a) Locus. Atherosclerosis. 2010;212:193-196.
- Hopewell, J, et al. Lipoprotein(a) Genetic Variants Associated with Coronary and Peripheral Vascular Disease but Not with Stroke Risk in the Heart Protection Study. Circ Cardiovasc Genet. 2011;4:68-73.
- Ladenson, P, et al. Use of the Thyroid Hormone Analogue Eprotirome in Statin-Treated Dyslipidemia. 2010;362:906-916.
- Hernandez,C, et al. Biological Variation of Lipoprotein(a) in a Diabetic Population. Analysis of the Causes and Clinical Implications. Clin Chem Lab Med. 2003;41(8):1075-80.
- Nazir DJ, McQueen MJ. Monthly Intra-individual Variation in Lipoprotein(a) in 22 Normal Subjects over 12 months. Clin Biochem. 1997;30(2):163-70.
- Garnotel, R, et al. Long-term Variability of Serum Lipoprotein(a) Concentrations in Healthy Fertile Women. Clin Chem Lab Med. 1998;36(5):317-21.
- Damani, SB and Topol, EJ. Emerging Genomic Applications in Coronary Artery Disease. JACC Cardiovasc Interv. 2011;4(5):473-82.
