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Aims: The selection of the most appropriate treatment for several diseases relies on a number of factors such as environment, age, gender, and nutrition. Additionally, the contribution of different genetic polymorphisms to treatment efficacy has been largely recognized. The lack of information on the pharmacogenetic profile of our population prompted us to analyze the frequency of polymorphisms known to be relevant to achieve treatment efficacy with different therapeutic agents in viral infectious diseases, such as Hepatitis C and AIDS., Results: The allelic frequencies for the wild-type variant of the genes analyzed were cytochrome P450 2B6 (CYP2B6; rs3745274; 516G) 0.618 (95% confidence interval [CI]: 0.523, 0.711), chemokine coreceptor 5 (CCR5; rs333) 0.961 (95% CI: 0.942, 0.98), histocompatibility complex P5 (HCP5; rs2395029; 335T) 0.971 (95% CI: 0.937, 1), and interleukin 28B (IL28B; rs12979860; 12007005C) 0.656 (95% CI: 0.564, 0.747), respectively., Conclusions: Our data indicate that the genetic profile of the population studied is similar to that reported for other Caucasian populations, with only slight differences for CYP2B6. Noteworthy, the considerable number of patients carrying CYP2B6 (516T) and IL28B (12007005T) alleles underlies the importance of considering pharmacogenetic testing before starting drug therapy protocols to prevent toxicity and/or lack of effectiveness in AIDS or hepatitis C virus infections.

Lesch-Nyhan disease is a genetic disorder of purine metabolism caused by defective activity of the enzyme hypoxanthine-guanine phosphoribosyl transferase (HPRT), resulting from mutation in the corresponding gene on the long arm of the X chromosome (Xq26). The classical phenotype, which includes spasticity, involuntary movements, developmental disability, and self-injurious behavior, occurs exclusively in males, while heterozygous, carrier females are clinically normal. We analyzed an Argentine family in which there were male and female siblings with clinically identical classic features of Lesch-Nyhan disease. The mother and an older daughter were carriers and had normal phenotypes. We identified the HPRT mutation in the family. It is a C --> T transition at position 508 of the cDNA (c.508 C --> T) that changes the CGA codon for Arg(169) to the TGA stop codon (R169X). The female patient was karyotypically normal and heterozygous for the mutation. She inherited the HPRT mutation from her mother, but she also had unexpected nonrandom inactivation of the paternal X chromosome carrying the normal HPRT gene. This additional genetic alteration is the cause of the clinical expression of disease in this female patient., (Copyright 2000 Academic Press.)