ABSTRACT
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.
ABSTRACT
The apolipoprotein B (APOB) gene contains several polymorphic sites described as risk modifiers for cardiovascular events. The objective of this study was to verify the association of the classic APOB Xba I polymorphism (rs693) with atherosclerotic risk factors in a segment of the Brazilian elderly population considering their usual dietary intake. Clinical and biochemical characteristics as well as total caloric and fat intake data were determined from 644 elderly individuals. Polymorphism analysis was performed by conventional polymerase chain reaction followed by enzyme restriction. Statistical analyses compared measures and proportions according to different APOB genotypic combinations. Statistically significant association was found between Xba I polymorphism and serum LDL, total cholesterol, and total lipid levels, with important elevations among T homozygotes compared to the other genotypes. There was homogeneity in all other parameters analyzed (including intake pattern), with a tendency for reduced levels of circulating apolipoprotein B among TT individuals. Our results pointed out that genetic variation in APOB affected the lipemic profile of elderly individuals in a context not biased by diet, generating a pattern suggestive of secretory disorder of lipoprotein particles, with possible implication in atherosclerotic risk.