The DOI matches its Crossref record; 32 of the 32 references it cites were found in a registry or an index.
Relative contribution of variation within the APOC3/A4/A5 gene cluster in determining plasma triglycerides
Abstract
Since triglycerides (TG) are a major independent risk factor for coronary heart disease, understanding their genetic and environmental determinants is of major importance. Mouse models indicate an inverse relationship between levels of the newly identified apolipoprotein AV (APOAV) and TG concentrations. We have examined the relative influence of human APOA5 variants on plasma lipids, compared to the impact of variation in APOC3 and APOA4 which lie in the same cluster. Single nucleotide polymorphisms (SNPs) in APOA5 (S19W, -1131T>C) and APOA4 (T347S, Q360H) and an APOA4/A5 intergenic T>C SNP were examined in a large study of healthy middle-aged men (n=2808). APOA5 19WW and -1131CC men had 52% and 40% higher TG (P<0.003) compared to common allele homozygotes, respectively, effects which were independent and additive. APOA4 347SS men had 23% lower TG compared to TT men (P<0.002). Haplotype analysis was carried out to identify TG-raising alleles and included, in addition, four previously genotyped APOC3 SNPs (-2845T>G, -482C>T, 1100C>T, and 3238C>G). The major TG-raising alleles were defined by APOA5 W19 and APOC3 -482T. This suggests that the TG-lowering effect of APOA4 S347 might merely reflect the strong negative linkage disequilibrium with the common alleles of these variants. Thus variation in APOA5 is associated with differences in TGs in healthy men, independent of those previously reported for APOC3, while association between APOA4 and TG reflects linkage disequilibrium with these sites. The molecular mechanisms for these effects remain to be determined.
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Cites
A New Statistical Method for Haplotype Reconstruction from Population Data
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No adjustments are needed for multiple comparisons.
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What's wrong with Bonferroni adjustments
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High-resolution haplotype structure in the human genome
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An Apolipoprotein Influencing Triglycerides in Humans and Mice Revealed by Comparative Sequencing
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Two independent apolipoprotein A5 haplotypes influence human plasma triglyceride levels
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Cited by
Hatori, M., Vollmers, C., Zarrinpar, A., DiTacchio, L., Bushong, E. A., Gill, S., Leblanc, M., Chaix, A., Joens, M., Fitzpatrick, J. A. J., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.04.019 · Cited by 1,986
Genetic determinants of plasma triglycerides
Johansen, C. T., Kathiresan, S., & Hegele, R. A. (2011) · Journal of Lipid Research · doi:10.1194/jlr.r009720 · Cited by 263
Moulin, P., Dufour, R., Averna, M., Arca, M., Cefalù, A. B., Noto, D., D'Erasmo, L., Di Costanzo, A., Marçais, C., Alvarez-Sala Walther, L. A., et al. (2018) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2018.06.814 · Cited by 247
Prieur, X., Coste, H., & Rodríguez, J. C. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m301302200 · Cited by 194
Lai, C.-Q., Demissie, S., Cupples, L. A., Zhu, Y., Adiconis, X., Parnell, L. D., Corella, D., & Ordovas, J. M. (2004) · Journal of Lipid Research · doi:10.1194/jlr.m400192-jlr200 · Cited by 163
Metadata
- Authors
- Talmud, P. J.
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2002-11-15
- Volume
- 11
- Issue
- 24
- Pages
- 3039-3046
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- OpenAlex
- W2162588312
- Cited by
- 365
- References
- 32
- FWCI
- 21.59
- Type
- journal article
- Language
- en
- Open access
- closed
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