Association of stearoyl-CoA desaturase 1 activity with familial combined hyperlipidemia

Abstract

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. © 2008 American Heart Association, Lnc.