A haplotype in the dipeptidyl peptidase 4 gene impacts glycemic-related traits of Brazilian older adults.

Dipeptidyl peptidase 4 (DPP4) regulates various physiological pathways and has a pivotal role in glucose homeostasis. The objective of this study was to verify the association of a haplotype constituted by two single nucleotide polymorphisms (rs2268894 and rs6741949) in the DPP4 gene with type 2 diabetes mellitus (T2DM) and fasting glycemia-related variables in a sample of Brazilian older adults, taking serum levels and enzymatic activity of DPP4 into account. Clinical, biochemical, and anthropometric characteristics as well as DPP4 serum levels and enzymatic activity were determined in 800 elderly (≥60 years old) individuals. Assessment of polymorphic sites was performed by real-time PCR whereas haplotypes were inferred from genotypic frequencies. Statistical analyses compared measures and proportions according to T2DM diagnosis and DPP4 haplotypic groups. The most common haplotype consisted of the T-rs2268894/G-rs6741949 string, which was 20% more frequent among non-diabetics. Considering non-diabetic patients alone, carriers of the T/G haplotype had significantly lower levels of blood glucose, insulin, HOMA-IR index, and DPP4 activity. Among diabetic patients, the T/G haplotype was associated with lower DPP4 levels whereas glycemic scores were not affected by allelic variants. Our results suggested that the genetic architecture of DPP4 affects the glycemic profile and DPP4 serum levels and activity among elderly individuals according to the presence or absence of T2DM, with a possible implication of the T/G haplotype to the risk of T2DM onset.

A haplotype in the dipeptidyl peptidase 4 gene impacts glycemic-related traits of Brazilian older adults

Dipeptidyl peptidase 4 (DPP4) regulates various physiological pathways and has a pivotal role in glucose homeostasis. The objective of this study was to verify the association of a haplotype constituted by two single nucleotide polymorphisms (rs2268894 and rs6741949) in the DPP4 gene with type 2 diabetes mellitus (T2DM) and fasting glycemia-related variables in a sample of Brazilian older adults, taking serum levels and enzymatic activity of DPP4 into account. Clinical, biochemical, and anthropometric characteristics as well as DPP4 serum levels and enzymatic activity were determined in 800 elderly (≥60 years old) individuals. Assessment of polymorphic sites was performed by real-time PCR whereas haplotypes were inferred from genotypic frequencies. Statistical analyses compared measures and proportions according to T2DM diagnosis and DPP4 haplotypic groups. The most common haplotype consisted of the T-rs2268894/G-rs6741949 string, which was 20% more frequent among non-diabetics. Considering non-diabetic patients alone, carriers of the T/G haplotype had significantly lower levels of blood glucose, insulin, HOMA-IR index, and DPP4 activity. Among diabetic patients, the T/G haplotype was associated with lower DPP4 levels whereas glycemic scores were not affected by allelic variants. Our results suggested that the genetic architecture of DPP4 affects the glycemic profile and DPP4 serum levels and activity among elderly individuals according to the presence or absence of T2DM, with a possible implication of the T/G haplotype to the risk of T2DM onset.

Parasite prolyl oligopeptidases and the challenge of designing chemotherapeuticals for Chagas disease, leishmaniasis and African trypanosomiasis.

The trypanosomatids Trypanosoma cruzi, Leishmania spp. and Trypanosoma brucei spp. cause Chagas disease, leishmaniasis and human African trypanosomiasis, respectively. It is estimated that over 10 million people worldwide suffer from these neglected diseases, posing enormous social and economic problems in endemic areas. There are no vaccines to prevent these infections and chemotherapies are not adequate. This picture indicates that new chemotherapeutic agents must be developed to treat these illnesses. For this purpose, understanding the biology of the pathogenic trypanosomatid- host cell interface is fundamental for molecular and functional characterization of virulence factors that may be used as targets for the development of inhibitors to be used for effective chemotherapy. In this context, it is well known that proteases have crucial functions for both metabolism and infectivity of pathogens and are thus potential drug targets. In this regard, prolyl oligopeptidase and oligopeptidase B, both members of the S9 serine protease family, have been shown to play important roles in the interactions of pathogenic protozoa with their mammalian hosts and may thus be considered targets for drug design. This review aims to discuss structural and functional properties of these intriguing enzymes and their potential as targets for the development of drugs against Chagas disease, leishmaniasis and African trypanosomiasis.