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Clinical Chemistry 45: 331-339, 1999;
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(Clinical Chemistry. 1999;45:331-339.)
© 1999 American Association for Clinical Chemistry, Inc.

Articles

Allele-specific Differences in Apolipoprotein C-III mRNA Expression in Human Liver

Harald Esterbauer1, Emanuel Hell2, Franz Krempler3 and Wolfgang Patsch1,a

1 Department of Laboratory Medicine, Landeskrankenanstalten Salzburg, Muellner Hauptstrasse 48, A-5020 Salzburg, Austria.
Departments of
2 Surgery and
3 Medicine, Krankenhaus Hallein, A-5400 Hallein, Austria.
a Author for correspondence. Fax 011 43 662 4482 885; e-mail w.patsch{at}lkasbg.gv.at

Background: Sequence variations at the apolipoprotein (apo)C-III gene locus have been associated with increased plasma triglycerides. In particular, the S2 allele of an SstI polymorphism in the 3' untranslated region has been associated with hypertriglyceridemia in many populations. The aim of this study was to determine whether the variant S2 allele is related to increased mRNA expression in vivo.

Methods: We measured allele-specific apoC-III expression in liver biopsies of five obese subjects, using restriction isotyping and a primer extension method, both based on the SstI polymorphism.

Results: The expression of mRNA by the S1 and S2 alleles was similar in two patients, whereas the mRNA encoded by the S2 allele was 14%, 26%, and 29% more abundant than the wild-type mRNA in the remaining three patients. Because other polymorphisms at the apoC-III gene locus have been implicated in the S2-associated hypertriglyceridemia, we determined apoC-III haplotypes comprising promoter polymorphisms at -935, -641, -630, -625, -482, -455, as well as the SstI sites and a BbvI site, both located in the 3' untranslated region. None of these polymorphisms nor any haplotype exhibited a perfect association with allele-specific expression, but variation at the T-482C site correlated in four of five subjects with the relative allele abundance.

Conclusion: These data provide preliminary evidence for allele-specific differences in apoC-III mRNA expression in vivo and suggest that such differences may contribute to associations of apoC-III gene polymorphisms with hypertriglyceridemia. ©1999 American Association for Clinical Chemistry




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