Gene-environment interactions in health and disease, a Portuguese survey.

Funder

Organizational Unit

Publications

Pharmacogenetic Profile of a South Portuguese Population: Results from the Pilot Study of the European Health Examination Survey in Portugal

Publication . Gaio, Vânia; Picanço, Isabel; Nunes, Baltazar; Fernandes, Aida; Mendonça, Francisco; Horta Correia, Filomena; Beleza, Álvaro; Gil, Ana Paula; Bourbon, Mafalda; Vicente, A.M.; Dias, Carlos Matias; Barreto da Silva, Marta

Background: The genetic inter-individual variability of drug response can lead to therapeutic failure or adverse drug reactions (ADRs). The aims of this study were to assess the pharmacogenetic profile of a South Portuguese population according to established dosing guidelines for commonly prescribed drugs and to compare it with that of previously genotyped populations. Methods: A cross-sectional study was developed in the context of the Portuguese Component of the European Health Examination Survey (EHES). A total of 47 pharmacogenetically relevant variants in 23 different genes were genotyped in 208 participants. Allelic and genotypic frequencies were calculated, and the pharmacogenetic profile of the participants was defined. A comparative analysis was conducted through electronic database search. Pairwise Fst calculations were performed to assess the genetic distance between populations. Results: We found a significant small differentiation between the Portuguese regional populations regarding CYP2C9 rs1057910, CYP2D6 rs3892097, MTHFR rs1801133 and F5 rs6025. When consid-ering 4 HapMap populations, ADH1B rs2066702, ADH1B rs1229984, NAT2 rs1799931 and VKORC1 rs9923231 displayed a significant population differentiation. We found that 18.9% of the participants are intermediate or poor metabolizers for at least 3 drugs simultaneously and that 84.6% of the participants have at least one therapeutic failure or ADR risk allele for the considered drugs. Conclusions: There is a high prevalence of risk alleles associated with an altered drug metabolism regarding drugs largely used by the South Portuguese population. This knowledge contributes to the prediction of their clinical efficacy and/or toxicity, optimizing therapeutic response while improving cost-effectiveness.

2015-10-03Journal article

Restricted access

Prevalence of diabetes-associated gene variants and its association with blood glucose levels in the Algarve population, Portugal

Publication . Gaio, Vania; Fernandes, Aida; Mendonça, Francisco; Horta Correia, Filomena; Beleza, Álvaro; Gil, Ana Paula; Bourbon, Mafalda; Vicente, A.M.; Barreto da Silva, Marta; Dias, Carlos Matias

The global rise in incidence of type 2 (T2D) has been called a pandemic, constituting a major public health concern. Although environmental factors play a substantial role in the etiology of T2D, genetic susceptibility has been established as a key component in T2D risk. Given the absence of studies regarding the prevalence of T2D associated variants in the Portuguese population, our aim was to determine the prevalence of disease-associated variants and determine its relative contribution to this phenotype. For this purpose, we have recruited 221 individuals (93 males and 128 females), between 26-91 years old (mean age 57.1), who were enrolled in the Health Centre of S. Brás de Alportel (Algarve). For each participant, we have measured total glucose levels and collected DNA. In addition, each participant has answered an exhaustive questionnaire including socio-demographic information, health history and lifestyle. We have selected and analysed three of the most significant loci previously reported to be associated with T2D in Caucasian populations (TCF7L2 rs7903146, PARPG rs1801282 and FTO rs9939609) and performed an association analysis between glucose levels in this population and the selected gene variants. The mean total population glucose level was 103.85±35.3 g/dl. We found a significant difference in the mean glucose levels between males (mean = 111.5±51.3 g/dl) and females (mean = 98.4±17.6 g/dl) (Mann-Whitney test P < 0.001). The relative allele frequencies of the genotyped variants have been established. Genotype distribution for all investigated SNPs was in Hardy-Weinberg equilibrium. We found a marginal association between glucose levels and genotypes at the TCF7L2 locus (Mann-Whitney test P = 0.045) in females but not in males, with carriers of the T allele displaying higher levels of blood glucose than homozygous for the A allele. This difference is also observed in males, although not reaching significance. No association was found between glucose levels and the other genotyped variants. These results suggest that the pathophysiology of the disease may be different between males and females, or that environmental factors are influencing this trait in males. We are currently investigating the later hypothesis by increasing our sample size and by analysing lifestyle information provided by the participants in order to evaluate gene-environment interactions influencing glucose levels in the Portuguese population.

2012-10-25Conference object

Open access