Linsel-Nitschke, Patrick and Goetz, Anika and Erdmann, Jeanette and Braenne, Ingrid and Braund, Peter and Hengstenberg, Christian and Stark, Klaus and Fischer, Marcus and Schreiber, Stefan and El Mokhtari, Nour Eddine and Schaefer, Arne and Schrezenmeier, Juergen and Rubin, Diana and Hinney, Anke and Reinehr, Thomas and Roth, Christian and Ortlepp, Jan and Hanrath, Peter and Hall, Alistair S. and Mangino, Massimo and Lieb, Wolfgang and Lamina, Claudia and Heid, Iris M. and Doering, Angela and Gieger, Christian and Peters, Annette and Meitinger, Thomas and Wichmann, H. -Erich and Koenig, Inke R. and Ziegler, Andreas and Kronenberg, Florian and Samani, Nilesh J. and Schunkert, Heribert (2008) Lifelong Reduction of LDL-Cholesterol Related to a Common Variant in the LDL-Receptor Gene Decreases the Risk of Coronary Artery Disease-A Mendelian Randomisation Study. PLOS ONE, 3 (8): e2986. ISSN 1932-6203,
Full text not available from this repository. (Request a copy)Abstract
Background: Rare mutations of the low-density lipoprotein receptor gene (LDLR) cause familial hypercholesterolemia, which increases the risk for coronary artery disease (CAD). Less is known about the implications of common genetic variation in the LDLR gene regarding the variability of cholesterol levels and risk of CAD. Methods: Imputed genotype data at the LDLR locus on 1 644 individuals of a population-based sample were explored for association with LDL-C level. Replication of association with LDL-C level was sought for the most significant single nucleotide polymorphism (SNP) within the LDLR gene in three European samples comprising 6 642 adults and 533 children. Association of this SNP with CAD was examined in six case-control studies involving more than 15 000 individuals. Findings: Each copy of the minor T allele of SNP rs2228671 within LDLR (frequency 11%) was related to a decrease of LDL-C levels by 0.19 mmol/L (95% confidence interval (CI) [0.13-0.24] mmol/L, p = 1.5x10(-10)). This association with LDL-C was uniformly found in children, men, and women of all samples studied. In parallel, the T allele of rs2228671 was associated with a significantly lower risk of CAD (Odds Ratio per copy of the T allele: 0.82, 95% CI [0.76-0.89], p = 2.1x10(-7)). Adjustment for LDL-C levels by logistic regression or Mendelian Randomisation models abolished the significant association between rs2228671 with CAD completely, indicating a functional link between the genetic variant at the LDLR gene locus, change in LDL-C and risk of CAD. Conclusion: A common variant at the LDLR gene locus affects LDL-C levels and, thereby, the risk for CAD.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GENOME-WIDE ASSOCIATION; HEART-DISEASE; CARDIOVASCULAR EVENTS; MYOCARDIAL-INFARCTION; EPIDEMIOLOGY; POLYMORPHISM; POPULATION; HYPERCHOLESTEROLEMIA; METAANALYSIS; PREVALENCE; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 26 Oct 2020 09:27 |
| Last Modified: | 26 Oct 2020 09:27 |
| URI: | https://pred.uni-regensburg.de/id/eprint/30467 |
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