Genetic variation in the quantitative levels of an NADP (H)-binding protein (FX) in human erythrocytes

FX is a red cell NADP(H)-binding protein that has been well defined biochemically and immunologically but whose function is still unknown. Preliminary data indicated that the levels of this protein are significantly increased in hemizygotes, heterozygotes, and homozygotes for the G6PD Mediterranean mutant, thus raising the question of whether or not the individual variation in FX levels is more or less directly influenced by X-linked genes. The present study, based on a large series of population and family data collected in Sardinia, confirms unequivocally the above mentioned interaction, but shows at the same time that the variances in FX levels “between sibships” are 2–3 times larger than those “within sibships,” when the analysis is done separately for the G6PD-normal or the G6PD-deficient sibs. From the comparison of the interclass and intraclass correlation coefficients, it appears that about 60% of the total variation of FX is of genetic origin. Moreover, the FX levels of children, analyzed in a pairwise manner, were found to be more positively correlated with those of their fathers (r = 0.39) than with those of their maternal grandfathers (0.20). This latter finding obviously favors the conclusion that “autosomal”; rather than “X-linked” genes are involved in the determination of the FX levels.