Distribution of ABCB1, CYP3A5, CYP2C19, and P2RY12 gene polymorphisms in a Mexican Mestizos population

The aim of the present study was to establish the gene frequency of six polymorphisms of the ABCB1, CYP3A5, CYP2C19, and P2RY12 genes in a population resident of Mexico City. The proteins encoded by these genes have been associated with the absorption, and biotransformation of clopidogrel. The ABCB1 T3435C, CYP3A5 V3* A6986G, P2RY12 G52T, P2RY12 C34T, CYP2C19 V2* and V3* (positions G681A and G636A, respectively), polymorphisms were analyzed by 5′ exonuclease TaqMan genotyping assays in a group of 269 healthy unrelated Mexican Mestizo individuals. The CYP2C19 V3* G636A polymorphism was not detected in the Mexican Mestizos population. However, the studied population presented significant differences (P < 0.05) in the distribution of the T3435C, A6986G, G681A, G52T and C34T polymorphisms when compared to reported frequencies of Amerindian of South America, Caucasian, Asian, and African populations. In summary, the distribution of the ABCB1, CYP3A5, CYP2C19, and P2RY12 gene polymorphisms distinguishes to the Mexican Mestizos population from other ethnic groups.     

Photic stimulation of the suprachiasmatic nucleus via the non-visual optic system. A gene expression study in the blind Crx −/− mouse

The visual system of vertebrates consists of an image-forming and a non-image-forming optic system; the image-forming optic system involves the classic photoreceptors, the rods and cones, whereas the non-image-forming optic system involves the melanopsin-containing retinal ganglion cells. Both optic systems make direct neuroanatomical connections to the suprachiasmatic nucleus (SCN) in the hypothalamus in which the biological clock of vertebrates is located. The rhythmic output from SCN neurons is entrained by light via the retina and the retinohypothalamic tract. The response of exposure to light during the subjective night is an immediate expression of several early response genes in the SCN. We show, by quantitative real-time polymerase chain reaction, that the amount of melanopsin mRNA in the retinal ganglion cells is preserved in the blind Crx ^?/? mouse with degenerated classic photoreceptors. At zeitgeber time 16, the Crx ^?/? and wild-type mice were exposed to 1 h of light. This resulted in a strong up-regulation of the immediate early genes Nr4a1, Erg, and Rrad in the SCN of both genotypes. Light stimulation during the subjective night resulted in a strong up-regulation of c-fos in both genotypes with a significantly higher up-regulation in the blind Crx ^?/? mouse. Expression of Grp and Vip, the genes for two classic peptides located in the SCN, was not influenced by light stimulation. The data strongly indicate the involvement of the melanopsin-based non-visual optic system in the regulation of immediate early genes in the SCN.