Variant carrier status is associated with reduced serum LDL-C and TC levels
| Rare variant group PCSK9/APOB MAF <0.01 | Non-carriers N=9540 | Heterozygotes N=104 | Homozygotes N=0 | P value |
| LDL-C (mg/dL) | 119.9 (96.7–143.1) | 108.3 (81.2–131.5) | – | <0.001 |
| adjLDL-C (mg/dL) | 131.5 (112.1–150.8) | 112.1 (92.8–139.2) | – | <0.001 |
| TC (mg/dL) | 201.1 (177.9–228.2) | 193.3 (170.1–220.4) | – | <0.001 |
| adjTC (mg/dL) | 217.5 (193.4–241.6) | 201.1 (177.9–225.7) | – | <0.001 |
| Common variant PCSK9 rs11591147-T | Non-carriers N=9540 | Heterozygotes N=465 | Homozygotes N=6 | P value |
| LDL-C (mg/dL) | 119.9 (96.7–143.1) | 112.1 (88.9–131.5) | 106.35 (95.7–117.0) | <0.001 |
| adjLDL-C (mg/dL) | 131.5 (112.1–150.8) | 116.0 (96.7–135.3) | 106.4 (95.7–117.0) | <0.001 |
| TC (mg/dL) | 201.1 (177.9–228.2) | 197.2 (170.1–216.6) | 197.2 (168.2–211.7) | <0.001 |
| adjTC (mg/dL) | 217.5 (193.4–241.6) | 201.1 (183.6–227.1) | 197.2 (168.2–211.7) | <0.001 |
We compared serum LDL-C and TC levels between variant carriers and n=9540 non-carrier controls from the ASPREE study. The multivariable linear regression model adjusted for age, gender, diabetes, hypertension, smoking status, alcohol use and body mass index. We first tested association using raw unadjusted LDL-C and TC levels (not accounting for statin use), then separately using statin-adjusted levels (adjLDL-C, adjTC), dividing LDL-C and TC levels by 0.7 and 0.8, respectively for those using statin medication to estimate untreated levels, as done previously.3 We identified statin users based on concomitant medications recorded by ASPREE at baseline. Data are presented as median (IQR). Statistical significance is denoted by p<0.001. To convert values from mg/dL to mmol/L multiply by 0.02586. ATC code C10 (lipid-modifying agents).
ASPREE, ASPirin in Reducing Events in the Elderly; ATC, Anatomical Therapeutic Chemical; LDL-C, low-density lipoprotein cholesterol; MAF, minor allele frequency; TC, total cholesterol.