Biological function and reliability analysis of RBP:TTR index as a biomarker of vitamin A status

We investigated the usefulness of RBP:TTR index (retinol binding protein:transthyretin) as a biomarker of vitamin A (VA) status assessment in pregnant women and also the biological variations (intra-individual and inter-individual) of RBP:TTR index by gender and time in order to calculate the index of individuality and determine its reliability to develop population-based reference interval compared to that of retinol. The study included two parts: (1) a cross-sectional study in pregnant women (n=259) from Nepal in their last trimester to assess their VA status using RBP:TTR index and the relationship of RBP:TTR index with free holo-RBP; and (2) a longitudinal study in clinically healthy young adults (n=40) with adequate VA intake to assess the reliability of RBP:TTR index and plasma retinol in developing population-based reference interval. As an extension of the longitudinal study, we also determined the effect of endogenous and exogenous female sexual hormones on the biological variations of retinol and RBP:TTR index of females (n=20). Our data demonstrated that: (1) the RBP:TTR index is a useful biomarker in VA status assessment of pregnant women; (2) the RBP:TTR index explains 75% of variance in free holo-RBP concentration and is a better predictor of free holo-RBP; (3) free holo-RBP concentration is higher in VA-sufficient compared to VA-deficient pregnant women and among VA-sufficient women, free holo-RBP concentration is higher in women with late gestation weeks; (4) intra-individual variation of RBP:TTR index is equal to or greater than the inter-individual variation and hence is sensitive to abnormal changes within an individual; (5) the index of individuality of RBP:TTR index is greater than 1.0 and is useful to develop population-based reference interval to assess the VA status of an individual with equal probability compared to plasma retinol; (6) the biological variations of females is affected by different phases of the menstrual cycle as well as the use of oral contraceptives. Our results warrant the need of future studies to assess the biological variation of RBP:TTR index in different age groups and population to assess its usefulness in developing a single population-based reference interval that can be used in different parts of the world.