Gene: LPA

Alternate names for this Gene: AK38|APOA|LP

Gene Summary: The protein encoded by this gene is a serine proteinase that inhibits the activity of tissue-type plasminogen activator I. The encoded protein constitutes a substantial portion of lipoprotein(a) and is proteolytically cleaved, resulting in fragments that attach to atherosclerotic lesions and promote thrombogenesis. Elevated plasma levels of this protein are linked to atherosclerosis. Depending on the individual, the encoded protein contains 2-43 copies of kringle-type domains. The allele represented here contains 15 copies of the kringle-type repeats and corresponds to that found in the reference genome sequence.

Gene is located in Chromosome: 6

Location in Chromosome : 6q25.3-q26

Description of this Gene: lipoprotein(a)

Type of Gene: protein-coding

rs10455872 in LPA gene and Acute Coronary Syndrome PMID 28753643 2017 Pharmacogenetic meta-analysis of baseline risk factors, pharmacodynamic, efficacy and tolerability endpoints from two large global cardiovascular outcomes trials for darapladib.

rs10455872 in LPA gene and Aortic valve calcification PMID 23388002 2013 One SNP in the lipoprotein(a) (LPA) locus (rs10455872) reached genomewide significance for the presence of aortic-valve calcification (odds ratio per allele, 2.05; P=9.0×10(-10)), a finding that was replicated in additional white European, African-American, and Hispanic-American cohorts (P<0.05 for all comparisons).

rs3798220 in LPA gene and CORONARY ARTERY DISEASE, AUTOSOMAL DOMINANT, 1 PMID 23202125 2013 Large-scale association analysis identifies new risk loci for coronary artery disease.

rs140570886 in LPA gene and Cardiovascular Diseases PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

rs10455872 in LPA gene and Cerebrovascular accident PMID 24262325 2014 Shared genetic susceptibility to ischemic stroke and coronary artery disease: a genome-wide analysis of common variants.

rs10455872 in LPA gene and Coronary Artery Disease PMID 28714975 2017 Association analyses based on false discovery rate implicate new loci for coronary artery disease.

PMID 19198611 2009 Genome-wide haplotype association study identifies the SLC22A3-LPAL2-LPA gene cluster as a risk locus for coronary artery disease.

PMID 29212778 2018 Identification of 64 Novel Genetic Loci Provides an Expanded View on the Genetic Architecture of Coronary Artery Disease.

PMID 28714974 2017 Genetic analysis in UK Biobank links insulin resistance and transendothelial migration pathways to coronary artery disease.

PMID 30104761 2018 Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.

PMID 26343387 2015 A comprehensive 1,000 Genomes-based genome-wide association meta-analysis of coronary artery disease.

PMID 31186284 2019 A genome-wide association study on lipoprotein (a) levels and coronary artery disease severity in a Chinese population.

PMID 30003307 2018 We found genome-wide significant evidence for association with CAD at the previously well-established LPA locus (lead variant: rs74617384; OR 1.38 [95% CI 1.26, 1.51], p = 3.2 × 10<sup>-12</sup>) and at 9p21 (lead variant: rs10811652; OR 1.19 [95% CI 1.13, 1.26], p = 6.0 × 10<sup>-11</sup>).

rs10455872 in LPA gene and Coronary heart disease PMID 24262325 2014 Shared genetic susceptibility to ischemic stroke and coronary artery disease: a genome-wide analysis of common variants.

PMID 21966275 2011 Large-scale gene-centric analysis identifies novel variants for coronary artery disease.

PMID 28753643 2017 Pharmacogenetic meta-analysis of baseline risk factors, pharmacodynamic, efficacy and tolerability endpoints from two large global cardiovascular outcomes trials for darapladib.

PMID 19198611 2009 Genome-wide haplotype association study identifies the SLC22A3-LPAL2-LPA gene cluster as a risk locus for coronary artery disease.

PMID 21378990 2011 Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease.

rs74617384 in LPA gene and Diabetes PMID 30003307 2018 Genome-wide association study of coronary artery disease among individuals with diabetes: the UK Biobank.

rs74617384 in LPA gene and Diabetes Mellitus PMID 30003307 2018 Genome-wide association study of coronary artery disease among individuals with diabetes: the UK Biobank.

rs191555775 in LPA gene and High density lipoprotein measurement PMID 29507422 2018 A large electronic-health-record-based genome-wide study of serum lipids.

PMID 25961943 2015 The impact of low-frequency and rare variants on lipid levels.

PMID 23063622 2012 Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci.

rs112842440 in LPA gene and Lipoprotein (a) measurement PMID 28512139 2017 A genome-wide association meta-analysis on lipoprotein (a) concentrations adjusted for apolipoprotein (a) isoforms.

PMID 26377243 2015 Genome- and exome-wide association study of serum lipoprotein (a) in the Jackson Heart Study.

PMID 30108283 2018 A study of Kibbutzim in Israel reveals risk factors for cardiometabolic traits and subtle population structure.

PMID 23696881 2013 Imputation of variants from the 1000 Genomes Project modestly improves known associations and can identify low-frequency variant-phenotype associations undetected by HapMap based imputation.

PMID 31186284 2019 A genome-wide association study on lipoprotein (a) levels and coronary artery disease severity in a Chinese population.

rs10455872 in LPA gene and Low density lipoprotein cholesterol measurement PMID 22629316 2012 Multi-ethnic analysis of lipid-associated loci: the NHLBI CARe project.

PMID 29507422 2018 A large electronic-health-record-based genome-wide study of serum lipids.

PMID 30275531 2018 Genetics of blood lipids among ~300,000 multi-ethnic participants of the Million Veteran Program.

PMID 31217584 2019 Genetic analyses of diverse populations improves discovery for complex traits.

PMID 23063622 2012 Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci.

PMID 25350695 2014 Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins.

PMID 30670697 2019 Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity.

rs10455872 in LPA gene and Myocardial Infarction PMID 26343387 2015 A comprehensive 1,000 Genomes-based genome-wide association meta-analysis of coronary artery disease.

rs118039278 in LPA gene and Peripheral Arterial Diseases PMID 31285632 2019 Genome-wide association study of peripheral artery disease in the Million Veteran Program.

rs10455872 in LPA gene and Rheumatic aortic stenosis PMID 29511194 2018 Genome-wide analysis yields new loci associating with aortic valve stenosis.

rs9355296 in LPA gene and Serum HDL cholesterol measurement PMID 23063622 2012 Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci.

rs10455872 in LPA gene and Serum LDL cholesterol measurement PMID 22629316 2012 Multi-ethnic analysis of lipid-associated loci: the NHLBI CARe project.

PMID 23063622 2012 Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci.

rs6919346 in LPA gene and Serum albumin measurement PMID 23281178 2013 A genome-wide assessment of variability in human serum metabolism.

rs10455872 in LPA gene and Serum total cholesterol measurement PMID 29507422 2018 A large electronic-health-record-based genome-wide study of serum lipids.

PMID 31217584 2019 Genetic analyses of diverse populations improves discovery for complex traits.

PMID 30275531 2018 Genetics of blood lipids among ~300,000 multi-ethnic participants of the Million Veteran Program.

PMID 23063622 2012 Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci.

PMID 28270201 2017 Exploration of haplotype research consortium imputation for genome-wide association studies in 20,032 Generation Scotland participants.

rs10455872 in LPA gene and Squamous cell carcinoma PMID 23103227 2012 Genetic variants at 6p21.1 and 7p15.3 are associated with risk of multiple cancers in Han Chinese.

rs41265930 in LPA gene and Triglycerides measurement PMID 30275531 2018 Genetics of blood lipids among ~300,000 multi-ethnic participants of the Million Veteran Program.

PMID 23063622 2012 Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci.

PMID 25961943 2015 The impact of low-frequency and rare variants on lipid levels.

rs10455872 in LPA gene and response to statin PMID 22331829 2012 Genetic determinants of statin-induced low-density lipoprotein cholesterol reduction: the Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial.