The metabolomic profile characteristic of the Atropine subjects with microalbuminuria was observed also in normoalbuminuric subjects with the allele of risk or protection, in two of the polymorphism analyzed. These two polymorphisms are linked to the ACE-I and the RPH3A genes. While the ACE-I gene has been very well characterized for many years and associated to UAE and to progression of renal diseases, the role of the RPH3A has not been clarified until recently. RPH3A is a RAB3A effector, small G protein that is thought to act at late stages of exocytosis. This small protein, present in neurons and in podocytes, confers specificity to vesicles. It is noteworthy that podocytes possess Rab3A and their specific effector rabphilin-3A, which is expressed only in cells capable of highly regulated exocytosis. It is well known that podocytes are involved in many glomerular functions and apart from the maintenance of the filtration barrier they are responsible for the turnover of glomerular basement membrane components and for the ability to produce a variety of cytokines and growth factors. Furthermore, in human proteinuric conditions, the expression of these molecules can increase, supporting the concept that the Rab3A-rabphilin-3A complex can play a role not only in normal but also in damaged podocytes, and consequently filtering albumin. The study should be considered within its limitations since it is a cross-sectional study, in which associations can result from chance, and no cause-effect can be assured. The sample size is small for a genetic association study in complex trait genetics and some of the reported associations may be by chance. Concerning the correction for multiple testing, it reduces the significance of the association, but considering: a) each measurement has been independently inquired through both unbiased high-throughput genomics and metabolomics; thus, the integrative strategy of both techniques allows 2,3-Butanedione monoxime combination of the strength and compensates for the limitations on each of the methods; b) the SNP selection was from previous studies with a positive association with UAE, and therefore the present can be considered as a replication study; c) the two polymorphisms, in the genes ACE-I and the RPH3A, have a similar ����metabolomic microalbuminuric profile���� we consider that all of this reduce the possibility that the association was by chance.