Vitamin A is linked to the expression of the AI-CIII-AIV gene cluster in familial combined hyperlipidemia

There is growing evidence of the capacity of vitamin A to regulate the expr ession of the genetic region that encodes apolipoproteins (apo) A-I, C-III, and A-IV. This region in turn has been proposed to modulate the expression of hyperlipidemia in the commonest genetic form of dyslipidemia, familial combined hyperlipidemia (FCHL). The hypothesis tested here was whether vita min A (retinol), by controlling the expression of the AI-CIII-AIV gene clus ter, plays a role in modulating the hyperlipidemic phenotype in FCHL, We ap proached the subject by studying three genetic variants of this region: a C -1100-T transition in exon 3 of the apoC-III gene, a G(3206)-T transversion in exon 4 of the apoC-III gene, and a G(-75)-A substitution in the promote r region of the apoA-I gene. The association between plasma vitamin A conce ntrations and differences in the plasma concentrations of apolipoproteins A -I and C-III based on the different genotypes was assessed in 48 FCHL patie nts and 74 of their normolipidemic relatives, The results indicated that th e subjects carrying genetic variants associated with increased concentratio ns of apoA-I and C-III (C-1100-T and G(-75)-A) also presented increased pla sma concentrations of vitamin A, This was only observed among the FCHL pati ents, which suggested that certain characteristics of these patients contri buted to this association, The G(3206)-T was not associated with changes in either apolipoprotein concentrations or in vitamin A.jlr In summary, we re port a relationship between genetically determined elevations of proteins o f the AI-CIII-AIV gene cluster and vitamin A in FCHL patients. More studies will be needed to confirm that vitamin A plays a role in FCHL which might also be important for its potential application to therapeutical approaches .-Ribalta, J., J. Girona, J. C. Vallve, A. E. La Ville, M. Heras, and L. Ma sana. Vitamin A is linked to the expression of the AI-CIII-AIV gene cluster in familial combined hyperlipidemia.