Role of Pharmacogenetics in Improving the Safety of Psychiatric Care by Predicting the Potential Risks of Mania in CYP2D6 Poor Metabolizers Diagnosed With Bipolar Disorder.

One of the main concerns in psychiatric care is safety related to drug management. Pharmacogenetics provides an important tool to assess causes that may have contributed the adverse events during psychiatric therapy. This study illustrates the potential of pharmacogenetics to identify those patients for which pharmacogenetic-guided therapy could be appropriate. It aimed to investigate CYP2D6 genotype in our psychiatric population to assess the value of introducing pharmacogenetics as a primary improvement for predicting side effects.A broad series of 224 psychiatric patients comprising psychotic disorders, depressive disturbances, bipolar disorders, and anxiety disorders was included. The patients were genotyped with the AmpliChip CYP450 Test to analyzing 33 allelic variants of the CYP2D6 gene.All bipolar patients with poor metabolizer status showed maniac switching when CYP2D6 substrates such as selective serotonin reuptake inhibitors were prescribed. No specific patterns were identified for adverse events for other disorders.We propose to utilize pharmacogenetic testing as an intervention to aid in the identification of patients who are at risk of developing affective switching in bipolar disorder treated with selective serotonin reuptake inhibitors, CYP2D6 substrates, and inhibitors.

Helicobacter pylori genotyping from American indigenous groups shows novel Amerindian vacA and cagA alleles and Asian, African and European admixture.

It is valuable to extend genotyping studies of Helicobacter pylori to strains from indigenous communities across the world to better define adaption, evolution, and associated diseases. We aimed to genetically characterize both human individuals and their infecting H. pylori from indigenous communities of Mexico, and to compare them with those from other human groups. We studied individuals from three indigenous groups, Tarahumaras from the North, Huichols from the West and Nahuas from the center of Mexico. Volunteers were sampled at their community site, DNA was isolated from white blood cells and mtDNA, Y-chromosome, and STR alleles were studied. H. pylori was cultured from gastric juice, and DNA extracted for genotyping of virulence and housekeeping genes. We found Amerindian mtDNA haplogroups (A, B, C, and D), Y-chromosome DYS19T, and Amerindian STRs alleles frequent in the three groups, confirming Amerindian ancestry in these Mexican groups. Concerning H.pylori cagA phylogenetic analyses, although most isolates were of the Western type, a new Amerindian cluster neither Western nor Asian, was formed by some indigenous Mexican, Colombian, Peruvian and Venezuelan isolates. Similarly, vacA phylogenetic analyses showed the existence of a novel Amerindian type in isolates from Alaska, Mexico and Colombia. With hspA strains from Mexico and other American groups clustered within the three major groups, Asian, African or European. Genotyping of housekeeping genes confirmed that Mexican strains formed a novel Asian-related Amerindian group together with strains from remote Amazon Aborigines. This study shows that Mexican indigenous people with Amerindian markers are colonized with H. pylori showing admixture of Asian, European and African strains in genes known to interact with the gastric mucosa. We present evidence of novel Amerindian cagA and vacA alleles in indigenous groups of North and South America.

Discovery of the nonfunctional CYP2D6 31 allele in Spanish, Puerto Rican, and US Hispanic populations.

BACKGROUND: CYP2D6 31 (4042G>A, R(440)H) is an allelic variant of the highly polymorphic cytochrome P450 2D6 enzyme that has been associated with reduced functional activity. The US Food and Drug Administration (FDA)-cleared AmpliChip CYP450 test detects the 4042G>A single nucleotide polymorphism (SNP) but an allele assignment could not be made in two Spanish and two Puerto Rican individuals heterozygous for 4042G>A, resulting in no-calls. We aimed to resolve the CYP2D6 31 no-calls, determine the allele haplotype, and corroborate that CYP2D6 31 is associated with a poor metabolizer phenotype. METHODS: CYP2D6 genotyping was carried out using the AmpliChip CYP450 test and long-range polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (RFLP) platforms. Allele haplotype was determined by cloning and sequence analysis. Allele frequencies were determined in five population samples. RESULTS: A 6.6-kb long-range PCR product comprising the entire CYP2D6 gene and flanking regions was sequenced to determine the CYP2D6 31 haplotype. Identical sequences were obtained from both Puerto Ricans selected for sequence analysis. One Spanish individual with a CYP2D6 4/31 genotype was phenotyped as a poor metabolizer with the CYP2D6 probe drug dextromethorphan (urinary ratio DM/DX=0.71). The frequency of CYP2D6 31 was determined in 176 Spanish (0.57%), 50 Puerto Rican (2.0%), and 150 Hispanic (0.33%) people. CYP2D6 31 was absent in 237 North American Caucasians and 154 African Americans. CONCLUSIONS: CYP2D6 31 was associated with poor metabolism of dextromethorphan in vivo, which is consistent with a previous report classifying this allelic variant as nonfunctional. The discovery of CYP2D6 31 in Spanish people only (or of Spanish ancestry) suggests that it may contribute to CYP2D6 variability in individuals of Spanish ancestry.