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 vita- min A to regulate the expression of the genetic region that encodes apolipoproteins (apo) A-I, C-III, and A-IV. This re- gion in turn has been proposed to modulate the expression of hyperlipidemia in the commonest genetic form of dyslip- idemia, familial combined hyperlipidemia (FCHL). The hy- pothesis tested here was whether vitamin A (retinol), by controlling the expression of the AI-CIII-AIV gene cluster, plays a role in modulating the hyperlipidemic phenotype in FCHL. We approached 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 2 75 -A substitution in the promoter region of the apoA-I gene. The association between plasma vitamin A concentrations and differences in the plasma concentra- tions of apolipoproteins A-I and C-III based on the differ- ent genotypes was assessed in 48 FCHL patients and 74 of their normolipidemic relatives. The results indicated that the subjects carrying genetic variants associated with in- creased concentrations of apoA-I and C-III (C 1100 -T and G 2 75 -A) also presented increased plasma concentrations of vitamin A. This was only observed among the FCHL pa- tients, which suggested that certain characteristics of these patients contributed to this association. The G 3206 -T was not associated with changes in either apolipoprotein con- centrations or in vitamin A. In summary, we report a rela- tionship between genetically determined elevations of pro- teins of the AI-CIII-AIV gene cluster and vitamin A in FCHL patients. More studies will be needed to confirm that vita- min 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. Masana. Vitamin A is linked to the expression of the AI-CIII-AIV gene cluster in familial combined hyperlip- idemia. J. Lipid Res. 1999. 40: 426-431.