Key result
APOC3 19X allele carriage is linked to ~71 mg/dL lower triglycerides and higher HDL-C.
Why the study?
The frequency and lipid profile associations of the rare APOC3 R19X null mutation in the general population were not well described.
Is the rare variant APOC3 R19X associated with cardio-protective lipid profiles in the general US population?
Cross-Sectional (n=20,726)
Yes
Is the rare variant APOC3 R19X associated with cardio-protective lipid profiles in the general US population?
The rare APOC3 R19X variant is present in the general US population across multiple racial/ethnic groups and is associated with a cardio-protective lipid profile, including lower triglycerides and higher HDL cholesterol.
Answers are grounded in this paper and cite their sources.
APOC3 R19X may support lipid genetic research across US groups; leaves open cardiovascular outcome implications and should not change practice.
Background— A founder mutation was recently discovered and described as conferring favorable lipid profiles and reduced subclinical atherosclerotic disease in a Pennsylvania Amish population. Preliminary data have suggested that this null mutation APOC3 R19X (rs76353203) is rare in the general population. Methods and Results— To better describe the frequency and lipid profile in the general population, we as part of the Population Architecture using Genomics and Epidemiology I Study and the Epidemiological Architecture for Genes Linked to Environment Study genotyped rs76353203 in 1113 Amish participants from Ohio and Indiana and 19 613 participants from the National Health and Nutrition Examination Surveys (NHANES III, 1999 to 2002, and 2007 to 2008). We found no carriers among the Ohio and Indiana Amish. Of the 19 613 NHANES participants, we identified 31 participants carrying the 19X allele, for an overall allele frequency of 0.08%. Among fasting adults, the 19X allele was associated with lower triglycerides (n=7603; β=−71.20; P =0.007) and higher high-density lipoprotein cholesterol (n=8891; β=15.65; P =0.0002) and, although not significant, lower low-density lipoprotein cholesterol (n=6502; β= -4.85; P =0.68) after adjustment for age, sex, and race/ethnicity. On average, 19X allele participants had approximately half the triglyceride levels (geometric means, 51.3 to 69.7 versus 134.6 to 141.3 mg/dL), >20% higher high-density lipoprotein cholesterol levels (geometric means, 56.8 to 74.4 versus 50.38 to 53.36 mg/dL), and lower low-density lipoprotein cholesterol levels (geometric means, 104.5 to 128.6 versus 116.1 to 125.7 mg/dL) compared with noncarrier participants. Conclusions— These data demonstrate that APOC3 19X exists in the general US population in multiple racial/ethnic groups and is associated with cardio-protective lipid profiles.
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Crawford et al. (2014) conducted a cross-sectional in Lipid profiles / Subclinical atherosclerosis risk (n=20,726). APOC3 19X allele (rs76353203) vs. Noncarrier participants was evaluated on Triglyceride levels among fasting adults (β -71.20, p=0.007). Carrying the APOC3 19X allele was associated with lower triglycerides (β=-71.20; P=0.007) and higher high-density lipoprotein cholesterol (β=15.65; P=0.0002) in the general US population.
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