TY - JOUR
T1 - Association of stearoyl-CoA desaturase 1 activity with familial combined hyperlipidemia
AU - Mar-Heyming, Rebecca
AU - Miyazaki, Makoto
AU - Weissglas-Volkov, Daphna
AU - Kolaitis, Nicholas A.
AU - Sadaat, Narimaan
AU - Plaisier, Christopher
AU - Pajukanta, Päivi
AU - Cantor, Rita M.
AU - De Bruin, Tjerk W.A.
AU - Ntainbi, James M.
AU - Lusis, Aidons J.
PY - 2008/6/1
Y1 - 2008/6/1
N2 - Objective -Stearoyl-CoA desaturase 1 (SCDl) is the rate-limiting enzyme involved in the synthesis of monounsaturated fatty acids, and in mice SCDl activity is associated with plasma triglyceride levels. We used the fatty acid desaturation index (the plasma ratio of 18:1/18:0) as a marker of SCDl activity to investigate the relationship of SCDl to familial combined hyperlipidemia (FCHL). Methods and Results-The fatty acid desaturation index was measured in 400 individuals from 18 extended FCIIL pedigrees. FCHL-affected individuals exhibited increased SCDl activity when compared to unrelated controls OP<0.0001). The fatty acid desaturation index was found to be highly heritable (h 2=0.48, P=2.2X10 -11) in this study sample. QTI.. analysis in 346 sibling pairs from. 18 FCHL families revealed suggestive linkage of the desaturation index to chromosomes 3p26.1 to 3pl.3 (z=2.7, /°=0.003), containing the peroxisome proliferator-activated receptor gamma (PPAR?) gene, and 20pl 1.21 to 20ql3.32 (z=l,7, P=OM), containing the hepatocyte nuclear factor 4, alpha (HNF4a) gene. A specific haplotype of HNF4a was found to be associated with the desaturation index in these FCHL families (P=0.002). Conclusion-Our results demonstrate that the fatty acid desaturation index is a highly heritable trait that is associated with the dyslipidemia observed in FCHL.
AB - Objective -Stearoyl-CoA desaturase 1 (SCDl) is the rate-limiting enzyme involved in the synthesis of monounsaturated fatty acids, and in mice SCDl activity is associated with plasma triglyceride levels. We used the fatty acid desaturation index (the plasma ratio of 18:1/18:0) as a marker of SCDl activity to investigate the relationship of SCDl to familial combined hyperlipidemia (FCHL). Methods and Results-The fatty acid desaturation index was measured in 400 individuals from 18 extended FCIIL pedigrees. FCHL-affected individuals exhibited increased SCDl activity when compared to unrelated controls OP<0.0001). The fatty acid desaturation index was found to be highly heritable (h 2=0.48, P=2.2X10 -11) in this study sample. QTI.. analysis in 346 sibling pairs from. 18 FCHL families revealed suggestive linkage of the desaturation index to chromosomes 3p26.1 to 3pl.3 (z=2.7, /°=0.003), containing the peroxisome proliferator-activated receptor gamma (PPAR?) gene, and 20pl 1.21 to 20ql3.32 (z=l,7, P=OM), containing the hepatocyte nuclear factor 4, alpha (HNF4a) gene. A specific haplotype of HNF4a was found to be associated with the desaturation index in these FCHL families (P=0.002). Conclusion-Our results demonstrate that the fatty acid desaturation index is a highly heritable trait that is associated with the dyslipidemia observed in FCHL.
KW - Familial combined hyperlipidemia
KW - Genetics
KW - Hepatocyte nuclear factor 4 alpha
KW - Peroxisome proliferator-activated receptor gamma
KW - Stearoyl-coa desaturase
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U2 - 10.1161/ATVBAHA.107.160150
DO - 10.1161/ATVBAHA.107.160150
M3 - Article
C2 - 18340007
AN - SCOPUS:44849099288
SN - 1079-5642
VL - 28
SP - 1193
EP - 1199
JO - Arteriosclerosis, thrombosis, and vascular biology
JF - Arteriosclerosis, thrombosis, and vascular biology
IS - 6
ER -