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Heritability of C-reactive protein and association with apolipoprotein E genotypes in Japanese Americans
M A Austin1, C Zhang, S E Humphries
1Department of Epidemiology, School of Public Health and Community Medicine, Box 357236, University of Washington, Seattle, WA 98195-7236, USA. maustin@u.washington.edu
Insights
Genetic factors influence C-reactive protein (CRP) levels, a marker for cardiovascular disease. This study in Japanese Americans found heritability of CRP levels and a potential link with APOE gene variations.
Area of Science:
- Genetics
- Cardiovascular Disease Epidemiology
- Metabolic Syndrome
Background:
- Elevated C-reactive protein (CRP) levels are established predictors of cardiovascular diseases, stroke, peripheral vascular disease, diabetes, and metabolic syndrome features.
- Previous heritability studies of CRP levels are limited, primarily focusing on Caucasian family samples.
Purpose of the Study:
- To estimate the heritability of C-reactive protein (CRP) levels in a Japanese American population.
- To investigate the association between C-reactive protein (CRP) levels and variations in the Apolipoprotein E (APOE) gene.
Main Methods:
- Analysis of data from 562 Japanese Americans across 68 extended kindreds.
- Calculation of correlation coefficients between relatives and heritability estimates for CRP levels.
- Examination of the relationship between CRP levels and APOE genotypes, with and without covariate adjustments.
Main Results:
- Heritability estimates for CRP levels were approximately 0.3 (p < 0.01), indicating significant genetic influence.
- A significant association was observed between unadjusted CRP levels and APOE genotypes (p = 0.02), with epsilon2 carriers showing the highest mean CRP.
- The association between CRP and APOE genotypes diminished after adjusting for covariates (p = 0.07).
Conclusions:
- Both genetic and environmental factors contribute to CRP levels in Asian Americans.
- Further research is necessary to elucidate the specific role of the APOE gene in the genetic determination of CRP levels.
Abstract:
Numerous studies have demonstrated that increased C-reactive protein (CRP) levels predict coronary heart disease, stroke, peripheral vascular disease, and diabetes, and are associated with features of the metabolic syndrome. Only three previous studies have investigated the heritability of CRP levels, primarily in samples of Caucasian families. The purpose of the present study was to estimate the magnitude of genetic influences on CRP levels, and to examine potential associations between variation in the APOE gene and CRP levels, using a sample of 562 individual Japanese Americans from 68 extended kindreds. In general, correlation coefficients between first-degree relatives for CRP were approximately 0.2, and spouse correlations did not differ from zero, consistent with genetic influences. Heritability estimates were approximately 0.3 (p < 0.01), even with adjustment for factors known to influence CRP levels. A significant relationship was seen between unadjusted CRP levels and APOE genotypes (p = 0.02), with the highest mean CRP level among epsilon2 carriers (1.20 mg/L), and nearly the same mean levels among epsilon3/epsilon3 subjects and epsilon4 carriers (0.72 and 0.74 mg/L, respectively). However, this relationship was diminished with adjustment for covariates (p = 0.07). These results demonstrate the presence of both genetic and environmental effects on CRP levels among Asian Americans, and additional studies are needed to determine if the APOE gene contributes to these genetic influences.
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