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
2008

Common Variant in LDL-Receptor Gene Reduces Cholesterol and Heart Disease Risk

Sample size: 1644 publication Evidence: high

Author Information

Author(s): Linsel-Nitschke Patrick, Götz Anika, Erdmann Jeanette, Braenne Ingrid, Braund Peter, Hengstenberg Christian, Stark Klaus, Fischer Marcus, Schreiber Stefan, El Mokhtari Nour Eddine, Schaefer Arne, Schrezenmeier Jürgen, Rubin Diana, Hinney Anke, Reinehr Thomas, Roth Christian, Ortlepp Jan, Hanrath Peter, Hall Alistair S., Mangino Massimo, Lieb Wolfgang, Lamina Claudia, Heid Iris M., Doering Angela, Gieger Christian, Peters Annette, Meitinger Thomas, Wichmann H.-Erich, König Inke R., Ziegler Andreas, Kronenberg Florian, Samani Nilesh J., Schunkert Heribert

Primary Institution: Medizinische Klinik II, Universität zu Lübeck, Lübeck, Germany

Hypothesis

Does a common genetic variant in the LDL-receptor gene affect cholesterol levels and the risk of coronary artery disease?

Conclusion

A common variant at the LDLR gene locus affects LDL-C levels and, thereby, the risk for coronary artery disease.

Supporting Evidence

  • Each copy of the minor T allele of SNP rs2228671 was related to a decrease of LDL-C levels by 0.19 mmol/L.
  • The T allele of rs2228671 was associated with a significantly lower risk of coronary artery disease.
  • The association with LDL-C was uniformly found in children, men, and women across all samples studied.
  • Adjustment for LDL-C levels abolished the significant association between rs2228671 and CAD.

Takeaway

Some people have a gene that helps keep their cholesterol low, which can help them avoid heart problems.

Methodology

The study analyzed genetic data from multiple populations to assess the association between a specific SNP in the LDLR gene and LDL-C levels and coronary artery disease risk.

Limitations

The study cannot mechanistically explain the decrease in LDL-C associated with the T-allele.

Participant Demographics

The study included adults and children from various European populations.

Statistical Information

P-Value

1.5×10−10

Confidence Interval

[0.13–0.24]

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1371/journal.pone.0002986

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