, Melissa Yssel, MB ChB, FC Path(SA) Chem
139, and Wendy M. Zakowicz, BS 79 Purpose: To achieve clinical validation of cutoff values for newborn screening by tandem mass spectrometry through a worldwide collaborative effort. Methods: Cumulative percentiles of amino acids and acylcarnitines in dried blood spots of approximately 25-30 million normal newborns and 10,742 deidentified true positive cases are compared to assign clinical significance, which is achieved when the median of a disorder range is, and usually markedly outside, either the 99th or the 1st percentile of the normal population. The cutoff target ranges of analytes and ratios are then defined as the interval between selected percentiles of the two populations. When overlaps occur, adjustments are made to maximize sensitivity and specificity taking all available factors into consideration.
Aims-Admixture in the population of the island of Puerto Rico is of general interest with regards to pharmacogenetics to develop comprehensive strategies for personalized healthcare in Latin Americans. This research was aimed at determining the frequencies of SNPs in key physiological, pharmacological and biochemical genes to infer population structure and ancestry in the Puerto Rican population.
Objective
This cross-sectional study was aimed at determining the allele frequencies for the CYP2C19*2, CYP2C19*3, CYP2D6*10 and PON1 (rs662) polymorphisms in the Puerto Rican population. The CYP2C19, CYP2D6 and PON1 genes are known to be associated with functional changes in drug metabolism and activation. Individuals carrying the aforementioned polymorphisms are at a higher risk of suffering from drug-induced adverse events and/ or unresponsiveness from a variety of drugs that includes antidepressants, atypical antipsychotics and antiplatelet compounds. Information on the frequency of these polymorphisms is more commonly found on homogeneous populations, but is scarce in highly heterogeneous populations like Hispanics, as in the case of Puerto Ricans.
Method
Genotyping was carried out in 100 genomic DNA samples from dried blood spots supplied by the Puerto Rican Newborn Screening program using Taqman® Genotyping Assays.
Results
The Minor Allele Frequencies (MAF) obtained were 9% for CYP2C19*2 and CYP2D6*10, 50% for PON1 (rs662), while the CYP2C19*3 variant was not detected in our study. Furthermore, Hardy Weinberg equilibrium analysis was assessed as well as a comparison between Puerto Rico and other reference populations using a Z-test for proportions.
Conclusion
The observed allele and genotype frequencies on these relevant pharmacogenes in Puerto Ricans were more closely related to those early reported in two other reference populations of Americans (Mexicans and Colombians).
DDAVP seldom improves the BT of Puerto Rican children with HPS. Response to DDAVP should be determined individually and platelet transfusion should remain the treatment of choice for a major bleeding episode or surgical procedure.
Our results revealed a correlation between plasmatic NO levels, systolic function and histopathological myocardial damage. Therefore, it is plausible to postulate that plasmatic NO levels could be used as a biomarker for myocardial damage in doxorubicin-treated SHR, and may be a potential tool for noninvasive evaluation of doxorubicin-induced toxicity in humans.
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