Association of plasma lipids and apolipoproteins with the insulin response element in the apoC-III promoter region in familial combined hyperlipidemia
The apoAI-CIII-AIV gene cluster, located on chromosome 11, contributes to the phenotype of familial combined hyperlipidemia (FCH), but this contribution is genetically complex. Combinations of haplotypes, based on three restriction enzyme polymorphisms: XmnI and MspI sites, 5′ of the start site of t...
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| Format: | Article |
| Language: | English |
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Elsevier
1999-06-01
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| Series: | Journal of Lipid Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520335070 |
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| author | M. Groenendijk R.M. Cantor N.H.H.C. Blom J.I. Rotter T.W.A. de Bruin G.M. Dallinga-Thie |
| author_facet | M. Groenendijk R.M. Cantor N.H.H.C. Blom J.I. Rotter T.W.A. de Bruin G.M. Dallinga-Thie |
| author_sort | M. Groenendijk |
| collection | DOAJ |
| description | The apoAI-CIII-AIV gene cluster, located on chromosome 11, contributes to the phenotype of familial combined hyperlipidemia (FCH), but this contribution is genetically complex. Combinations of haplotypes, based on three restriction enzyme polymorphisms: XmnI and MspI sites, 5′ of the start site of the apoA-I gene and SstI polymorphism in the 3′ untranslated region of exon 4 of the apoC-III gene, were analyzed to characterize their effect on the expression of severe hyperlipidemia. An epistatic interaction was demonstrated: the S2 allele on one haplotype was synergistic in its hyperlipidemic effect to the X2M2 allele on the other haplotype (Dallinga-Thie, G. M. et al. J. Clin. Invest. 1997. 99: 953–961). In the present study two additional polymorphic sites in the insulin response element (IRE) of the apoC-III gene promoter, T-455C: FokI restriction site, C-482T: MspI restriction site, were studied in 34 FCH pedigrees including 34 probands, 220 hyperlipidemic relatives, 300 normolipidemic relatives, and 236 spouses. In contrast to the earlier data for the other polymorphisms in this gene cluster (XmnI, MspI/AI, and SstI), there were no differences in frequency distributions of the T-455C and the C-482T variants between probands, hyperlipidemic and normolipidemic relatives and spouses. No significant associations between plasma lipid traits and DNA variants in the IRE were observed. Analysis of combinations of haplotypes based on the five polymorphisms in the gene cluster provided further evidence for a dominant role of the SstI polymorphism as a major susceptibility locus in FCH. The inclusion of the IRE markers did not improve genetic informativeness, nor our understanding of the observed synergistic relationship associated with the high risk combination of haplotypes in FCH families.—Groenendijk, M., R. M. Cantor, N. H. H. C. Blom, J. I. Rotter, T. W. A. de Bruin, and G. M. Dallinga-Thie. Association of plasma lipids and apolipoproteins with the insulin response element in the apoC-III promoter region in familial combined hyperlipidemia. J. Lipid Res. 1999. 40: 1036–1044. |
| first_indexed | 2024-12-17T19:07:55Z |
| format | Article |
| id | doaj.art-f6274cbe209c492994c8c80ad3499bc2 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-17T19:07:55Z |
| publishDate | 1999-06-01 |
| publisher | Elsevier |
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| series | Journal of Lipid Research |
| spelling | doaj.art-f6274cbe209c492994c8c80ad3499bc22022-12-21T21:35:57ZengElsevierJournal of Lipid Research0022-22751999-06-0140610361044Association of plasma lipids and apolipoproteins with the insulin response element in the apoC-III promoter region in familial combined hyperlipidemiaM. Groenendijk0R.M. Cantor1N.H.H.C. Blom2J.I. Rotter3T.W.A. de Bruin4G.M. Dallinga-Thie5Department of Internal Medicine, University Hospital Utrecht, P.O. Box 85500, 3508 GA Utrecht, the NetherlandsDepartment of Internal Medicine, University Hospital Utrecht, P.O. Box 85500, 3508 GA Utrecht, the NetherlandsDepartment of Internal Medicine, University Hospital Utrecht, P.O. Box 85500, 3508 GA Utrecht, the NetherlandsDivision of Medical Genetics, Departments of Medicine and Pediatrics, Cedars-Sinai Institute, Los Angeles, CA 90048Departments of Internal Medicine and Endocrinology, Academic Hospital Maastricht, Maastricht, the NetherlandsTo whom correspondence should be addressed.; Department of Internal Medicine, University Hospital Utrecht, P.O. Box 85500, 3508 GA Utrecht, the NetherlandsThe apoAI-CIII-AIV gene cluster, located on chromosome 11, contributes to the phenotype of familial combined hyperlipidemia (FCH), but this contribution is genetically complex. Combinations of haplotypes, based on three restriction enzyme polymorphisms: XmnI and MspI sites, 5′ of the start site of the apoA-I gene and SstI polymorphism in the 3′ untranslated region of exon 4 of the apoC-III gene, were analyzed to characterize their effect on the expression of severe hyperlipidemia. An epistatic interaction was demonstrated: the S2 allele on one haplotype was synergistic in its hyperlipidemic effect to the X2M2 allele on the other haplotype (Dallinga-Thie, G. M. et al. J. Clin. Invest. 1997. 99: 953–961). In the present study two additional polymorphic sites in the insulin response element (IRE) of the apoC-III gene promoter, T-455C: FokI restriction site, C-482T: MspI restriction site, were studied in 34 FCH pedigrees including 34 probands, 220 hyperlipidemic relatives, 300 normolipidemic relatives, and 236 spouses. In contrast to the earlier data for the other polymorphisms in this gene cluster (XmnI, MspI/AI, and SstI), there were no differences in frequency distributions of the T-455C and the C-482T variants between probands, hyperlipidemic and normolipidemic relatives and spouses. No significant associations between plasma lipid traits and DNA variants in the IRE were observed. Analysis of combinations of haplotypes based on the five polymorphisms in the gene cluster provided further evidence for a dominant role of the SstI polymorphism as a major susceptibility locus in FCH. The inclusion of the IRE markers did not improve genetic informativeness, nor our understanding of the observed synergistic relationship associated with the high risk combination of haplotypes in FCH families.—Groenendijk, M., R. M. Cantor, N. H. H. C. Blom, J. I. Rotter, T. W. A. de Bruin, and G. M. Dallinga-Thie. Association of plasma lipids and apolipoproteins with the insulin response element in the apoC-III promoter region in familial combined hyperlipidemia. J. Lipid Res. 1999. 40: 1036–1044.http://www.sciencedirect.com/science/article/pii/S0022227520335070familial combined hyperlipidemiaapolipoprotein CIIIinsulin response elementgene–gene interaction |
| spellingShingle | M. Groenendijk R.M. Cantor N.H.H.C. Blom J.I. Rotter T.W.A. de Bruin G.M. Dallinga-Thie Association of plasma lipids and apolipoproteins with the insulin response element in the apoC-III promoter region in familial combined hyperlipidemia Journal of Lipid Research familial combined hyperlipidemia apolipoprotein CIII insulin response element gene–gene interaction |
| title | Association of plasma lipids and apolipoproteins with the insulin response element in the apoC-III promoter region in familial combined hyperlipidemia |
| title_full | Association of plasma lipids and apolipoproteins with the insulin response element in the apoC-III promoter region in familial combined hyperlipidemia |
| title_fullStr | Association of plasma lipids and apolipoproteins with the insulin response element in the apoC-III promoter region in familial combined hyperlipidemia |
| title_full_unstemmed | Association of plasma lipids and apolipoproteins with the insulin response element in the apoC-III promoter region in familial combined hyperlipidemia |
| title_short | Association of plasma lipids and apolipoproteins with the insulin response element in the apoC-III promoter region in familial combined hyperlipidemia |
| title_sort | association of plasma lipids and apolipoproteins with the insulin response element in the apoc iii promoter region in familial combined hyperlipidemia |
| topic | familial combined hyperlipidemia apolipoprotein CIII insulin response element gene–gene interaction |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520335070 |
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