Abstract | OBJECTIVE: METHODS AND RESULTS: The fatty acid desaturation index was measured in 400 individuals from 18 extended FCHL pedigrees. FCHL-affected individuals exhibited increased SCD1 activity when compared to unrelated controls (P < 0.0001). The fatty acid desaturation index was found to be highly heritable (h(2) = 0.48, P = 2.2 x 10(-11)) in this study sample. QTL analysis in 346 sibling pairs from 18 FCHL families revealed suggestive linkage of the desaturation index to chromosomes 3p26.1 to 3p13 (z = 2.7, P = 0.003), containing the peroxisome proliferator-activated receptor gamma ( PPARgamma) gene, and 20p11.21 to 20q13.32 (z = 1.7, P = 0.04), containing the hepatocyte nuclear factor 4, alpha (HNF4alpha) gene. A specific haplotype of HNF4alpha was found to be associated with the desaturation index in these FCHL families (P = 0.002). CONCLUSIONS: Our results demonstrate that the fatty acid desaturation index is a highly heritable trait that is associated with the dyslipidemia observed in FCHL.
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Authors | Rebecca Mar-Heyming, Makoto Miyazaki, Daphna Weissglas-Volkov, Nicholas A Kolaitis, Narimaan Sadaat, Christopher Plaisier, Päivi Pajukanta, Rita M Cantor, Tjerk W A de Bruin, James M Ntambi, Aldons J Lusis |
Journal | Arteriosclerosis, thrombosis, and vascular biology
(Arterioscler Thromb Vasc Biol)
Vol. 28
Issue 6
Pg. 1193-9
(Jun 2008)
ISSN: 1524-4636 [Electronic] United States |
PMID | 18340007
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Fatty Acids
- HNF4A protein, human
- Hepatocyte Nuclear Factor 4
- PPAR gamma
- SCD1 protein, human
- Stearoyl-CoA Desaturase
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Topics |
- Adult
- Chromosome Mapping
- Dyslipidemias
(genetics)
- Fatty Acids
(metabolism)
- Female
- Haplotypes
(genetics)
- Hepatocyte Nuclear Factor 4
(genetics)
- Humans
- Hyperlipidemia, Familial Combined
(enzymology, genetics)
- Linkage Disequilibrium
(genetics)
- Male
- Middle Aged
- PPAR gamma
(genetics)
- Pedigree
- Stearoyl-CoA Desaturase
(genetics, metabolism)
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