Exploration of gene variations in the transcytosis system as a policy proposal for the personalized therapy in type 2 diabetes mellitus

Abstract

The gene system of transcytosis, integrated by LRP2, AMN, CUBN, ARH, AMN and CUBN, might be important for the treatment and monitoring of chronic complications of diabetics, as well as for drug interactions, since they mediate the reuptake of vitamins such as B complex, folic acid and lipoproteins, which are closely related to the progression of diabetes. That is why polymorphisms in those genes could be targets of personalized medicine, to improve the quality of health care. It is important for both the clinical researcher and physician to explore new personalized treatment options for better care of the diabetic patient. The search for genetic or genomic markers in order to predict complications of disease, progression as well as to evaluate the therapeutic response to drugs and the presentation of adverse effects is an area to be explored, considering the high costs that represent the attention of diabetics to hospitals from the public sector. Other reasons are that type 2 diabetes mellitus (T2D) patients develop complications related with the progression of the disease, as well as, adverse and side effects resulting from drug interactions [1,2]. T2D commonly presents deficiency of vitamin B complex, associated with the long-term consumption of metformin. The consequences of this deficiency are increased cardiovascular risk, renal damage and higher risk of peripheral neuropathy and senile dementia [1,2]. Additionally, the chronic consumption of statins for the control of hypercholesterolemia and cardiovascular risk results in secondary dyslipidemia myocytes inflammation [1,2].The common element that might explain the previously described complications and side effects in T2D diabetic patients is an axis of genes that encode for the system of transcytosis in the cellular membranes from small intestine, kidney, liver, striated muscle, and other tissues. The components of this transcytosis system are LRP2, AMN, CUBN, ARH, Dab2, GIPC, NHE3, ClC5, FcRn and NaPi-IIa, which mediate the reuptake of B complex vitamins, including folic acid among other molecules [3][4][5][6][7][8][9][10].The clinical effect of these genes might be seen in the development of different diseases or clinical conditions (Table 1). Mutations in LRP2 have been associated with diabetes, aminoglucosides response, DonnaiBarrow syndrome (DBS), Facio-oculo-acoustic-renal syndrome (FOAR) and Alzheimer's disease. While mutations in AMN and CUB occur with megaloblastic anemia plus albuminuria. CUBallelic variants are related to the progression of renal damage and ARH variations are associated with hypercholesterolemia [3][4][5][6][7][8][9][10]. NHE3 mutations show association with congenital sodium diarrhea, whereas ClC5 gene is related to renal failure or Dent disease. ClC5, FcRn, NaPi-IIa gene are related with metabolic renal disease. DAB2, GIPC has an uncertain meaning in human pathology, but their pathogenic effect must be explored [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25].Considering the interaction between these genes...

Insights in the Nutrigenetic, New Candidate Genes in Nutritional Diseases (Lrp2, Cubn, Amn, Atxn2, Tjp1, Elmo1)

“…This may be explained since cyanocobalamin binds to these two factors to be endocytosed at the intestinal level as well as in the proximal convoluted tubule. But it also determines the absorption of complex b, so when there is a deficit of these proteins or alterations in its structure translates into megaloblastic anemia [1]. Functional polymorphisms (coding region, cryptic sites, introns, promoter or enhancer) become important in the nutritional management of microcytic, megaloblastic or pluricarential anemia.…”