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Common genetic variants do not associate with CAD in familial hypercholesterolemia
Erik P A van Iperen1, Suthesh Sivapalaratnam2, S Matthijs Boekholdt3
11] Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Centre, Amsterdam, The Netherlands [2] Durrer Center for Cardiogenetic Research, Amsterdam, The Netherlands.
European Journal of Human Genetics : EJHG
|November 14, 2013
Summary
Common genetic variants linked to coronary artery disease (CAD) were studied in familial hypercholesterolemia (FH) patients. A surprising negative association was found with the SMARCA4 gene near the LDLR gene, contrary to expectations.
Area of Science:
- Genetics
- Cardiovascular Medicine
- Epidemiology
Background:
- Coronary artery disease (CAD) is associated with multiple genetic loci.
- Familial hypercholesterolemia (FH) is a high-risk group for CAD.
- The predictive value of known CAD genetic variants in FH cohorts requires further investigation.
Purpose of the Study:
- To evaluate the predictive value of common genetic variants for CAD in a large cohort of FH patients.
- To identify specific single-nucleotide polymorphisms (SNPs) associated with CAD risk in this high-risk population.
- To explore the association between known CAD loci and event-free survival in FH.
Main Methods:
- Genotyping of 41 single-nucleotide polymorphisms (SNPs) in 1701 FH patients.
- Analysis of event-free survival time using Cox proportional hazard models.
- Adjustment for cardiovascular disease risk factors in the statistical analysis.
Main Results:
- The SNP rs1122608:G>T in the SMARCA4 gene showed a significant negative association with CAD risk (HR 0.74, P=0.021).
- This association was contrary to the expected risk.
- No other analyzed CAD loci demonstrated a significant association with CAD in the FH cohort.
- None of the SNPs reached the Bonferroni significance threshold.
Conclusions:
- The SMARCA4 locus near the LDLR gene exhibited the strongest association with CAD in this FH cohort, unexpectedly showing a protective effect.
- The investigated common genetic variants, except for SMARCA4, did not demonstrate predictive value for CAD in FH patients.
- Further research is needed to understand the mechanisms behind the observed protective association of SMARCA4 in FH patients.
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