Apolipoprotein(a) isoform size, lipoprotein(a) concentration, and coronary artery disease: a mendelian randomisation analysis

Autor: Joseph L. Witztum, Zia Yaqoob, Santica M. Marcovina, Manjinder S. Sandhu, Asif Rasheed, Danish Saleheen, Sotirios Tsimikas, Faisal Majeed, Atif Imran, Fazal-ur-Rehman Memon, Khan Shah Zaman, Philippe M. Frossard, Anis Memon, Daniel J. Rader, Syed Zahed Rasheed, Naveeduddin Ahmed, Saba Akhtar, John Danesh, M. Ishaq, Tahir Saghir, Syed Nadeem Hasan Rizvi, Adam Taleb, Nadeem Qamar, Philip C Haycock, Wei Zhao, Nadeem Hayyat Mallick, Shahid Abbas, Khalid Mahmood
Přispěvatelé: Sandhu, Manjinder [0000-0002-2725-142X], Danesh, John [0000-0003-1158-6791], Apollo - University of Cambridge Repository
Rok vydání: 2017
Předmět:
0301 basic medicine
Male
medicine.medical_specialty
Apolipoprotein B
Genotype
Endocrinology
Diabetes and Metabolism
Myocardial Infarction
Coronary Disease
030204 cardiovascular system & hematology
Apoprotein(a)
Polymorphism
Single Nucleotide
Coronary artery disease
03 medical and health sciences
0302 clinical medicine
Endocrinology
Polymorphism (computer science)
Risk Factors
Internal medicine
Internal Medicine
medicine
Humans
Protein Isoforms
Genetic Predisposition to Disease
Pakistan
Myocardial infarction
biology
business.industry
Incidence
Case-control study
Articles
Odds ratio
Lipoprotein(a)
Mendelian Randomization Analysis
Middle Aged
medicine.disease
3. Good health
030104 developmental biology
Phenotype
Case-Control Studies
biology.protein
lipids (amino acids
peptides
and proteins)
Female
business
Biomarkers
Lipoprotein
Zdroj: The Lancet. Diabetes & Endocrinology
Saleheen, D, Haycock, P C, Zhao, W, Rasheed, A, Taleb, A, Imran, A, Abbas, S, Majeed, F, Akhtar, S, Qamar, N, Zaman, K S, Yaqoob, Z, Saghir, T, Rizvi, S N H, Memon, A, Mallick, N H, Ishaq, M, Rasheed, S Z, Memon, F-R, Mahmood, K, Ahmed, N, Frossard, P, Tsimikas, S, Witztum, J L, Marcovina, S, Sandhu, M, Rader, D J & Danesh, J 2017, ' Apolipoprotein(a) isoform size, lipoprotein(a) concentration, and coronary artery disease : a mendelian randomisation analysis ', Lancet Diabetes and Endocrinology, vol. 5, no. 7, pp. 524-533 . https://doi.org/10.1016/S2213-8587(17)30088-8
DOI: 10.1016/S2213-8587(17)30088-8
Popis: Background The lipoprotein(a) pathway is a causal factor in coronary heart disease. We used a genetic approach to distinguish the relevance of two distinct components of this pathway, apolipoprotein(a) isoform size and circulating lipoprotein(a) concentration, to coronary heart disease. Methods In this mendelian randomisation study, we measured lipoprotein(a) concentration and determined apolipoprotein(a) isoform size with a genetic method (kringle IV type 2 [KIV2] repeats in the LPA gene) and a serum-based electrophoretic assay in patients and controls (frequency matched for age and sex) from the Pakistan Risk of Myocardial Infarction Study (PROMIS). We calculated odds ratios (ORs) for myocardial infarction per 1-SD difference in either LPA KIV2 repeats or lipoprotein(a) concentration. In a genome-wide analysis of up to 17 503 participants in PROMIS, we identified genetic variants associated with either apolipoprotein(a) isoform size or lipoprotein(a) concentration. Using a mendelian randomisation study design and genetic data on 60 801 patients with coronary heart disease and 123 504 controls from the CARDIoGRAMplusC4D consortium, we calculated ORs for myocardial infarction with variants that produced similar differences in either apolipoprotein(a) isoform size in serum or lipoprotein(a) concentration. Finally, we compared phenotypic versus genotypic ORs to estimate whether apolipoprotein(a) isoform size, lipoprotein(a) concentration, or both were causally associated with coronary heart disease. Findings The PROMIS cohort included 9015 patients with acute myocardial infarction and 8629 matched controls. In participants for whom KIV2 repeat and lipoprotein(a) data were available, the OR for myocardial infarction was 0·93 (95% CI 0·90–0·97; p
Databáze: OpenAIRE
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