Pharmacogenetically relevant polymorphisms in Portugal

Most drugs are developed based on data from European-derived 'reference' populations; however, clinically relevant DNA polymorphisms often demonstrate population-specific patterns of allele frequencies. Given that the knowledge of the frequency distribution of functional polymorphisms in a population may guide national planning for selection of therapeutic options, in the present study we examined the allele frequencies of enzymes responsible for drug disposition in Portugal.

Using PCR- and Pyrosequencing-based methods, the current study assessed the frequencies of 15 key polymorphisms from genes encoding enzymes involved in Phases I, II and III of drug metabolism, DNA repair and intracellular metabolism in 135 healthy individuals from Portugal.

Allele frequencies were derived for cytochrome P450 (CYP)2C9*2 (13.2%), CYP2C9*3 (8%), CYP2C19*2 (14%), CYP3A4*1B (7%), CYP3A5*3C (87.5%), glutathione S-transferase (GST)M1*0 (77.9%), GSTP1 313A>G (33%), inosine triphosphatase 94C>A (7%), UDP-glucuronosyltransferase (UGT)1A1*28 (28%), UGT1A1 -3156G>A (23%), ATP-binding cassette (ABC)B1 1236C>T (46%), ABCB1 2677G>A/T (2 and 42%), ABCG2 421C>A (8%), excision repair cross-complementing rodent repair deficiency 2 2251A>C (3%) and thymidylate synthetase 1494del (31%).

Although, on the whole, the frequency distributions among the Portuguese fitted the patterns commonly found in other Europeans well, evidence for some degree of African influence was observed. This is the most comprehensive study on pharmacogenetically relevant variations in Portugal to date, and the baseline of pharmacogenetic data might be important for determining policy guidelines for cancer prevention and drug treatments in the Portuguese population.