Genetically determined dyslipidemia associated with abdominal aortic aneurysm
Genetic Association of Lipids and Lipid Drug Targets With Abdominal Aortic Aneurysm - A Meta-analysisLiterature - Harrison SC, Holmes MV, Burgess S, et al. - JAMA Cardiol 2017; published online ahead of print
- The LDL-c-lowering alleles of rs6511720 in LDLR (OR per allele: 0.75; 95% CI: 0.67-0.83; P=5.2 × 10−12) and rs646776 in SORT1 (OR per allele: 0.88; 95% CI: 0.82-0.94; P=3.9 × 10−8) were strongly associated with AAA.
- No other SNP from the 180 lipid associated SNPs was individually associated with AAA at conventional levels of genome-wide significance.
- The LDL-GRS was strongly associated with the AAA risk (OR per SD higher level for LDL-c: 1.66; 95% CI: 1.41-1.96; P=1.1 × 10−9). A 1-SD higher HDL-c level was associated with a reduced AAA risk (OR: 0.67; 95% CI: 0.55-0.82; P=8.3 × 10−5), and the TG-GRS was associated with higher AAA risk (OR per 1-SD higher TG level: 1.69; 95% CI: 1.38-2.07; P=5.2 × 10−7).
- None of the sensitivity MR analyses resulted in an important change to the magnitude or to the significance of the estimates.
- The LDL-c–lowering allele of rs12916 (to proxy statin use) was associated with a lower AAA risk in meta-analysis (OR per LDL-c–lowering allele: 0.93; 95% CI: 0.89-0.98; P=0.009).
- Examination of two independent SNPs in PCSK9 showed that the LDL-c–lowering allele of rs2479409 was not associated with AAA risk (OR: 0.97; 95% CI: 0.84-1.02; P=0.28), and the LDL-c–lowering allele of rs11206510 in PCSK9 was weakly associated with AAA risk (OR: 0.94; 95% CI: 0.88-1.00; P=0.04).
- The rs3764261 allele, as a proxy for CETP inhibition, was associated with lower AAA risk (OR per HDL-c–raising allele: 0.89; 95% CI: 0.85-0.94; P=3.7 × 10−7). However, the allele is also associated with lower TG and LDL-c concentrations, and therefore can give insight into the potential associations with CETP inhibition.
In a meta-analysis of 5 GWASs, the genetic elevation of LDL-c and TG levels was associated with an increased risk of AAA, whereas increased HDL-c level was associated with a lower risk of AAA. These results suggest that patients with an AAA have a high burden of genetically determined dyslipidemia; appropriate treatment of this may lower their AAA risk.