Tomaz Zupanc

Cyclooxygenase in normal human tissues – is COX-1 really a constitutive isoform, and COX-2 an inducible isoform?

Cyclooxygenase (COX) is a key enzyme in prostanoid synthesis. It exists in two isoforms, COX‐1 and COX‐2. COX‐1 is referred to as a ‘constitutive isoform’, and is considered to be expressed in most tissues under basal conditions. In contrast, COX‐2 is referred to as an ‘inducible isoform’, which is believed to be undetectable in most normal tissues, but can be up‐regulated during various conditions, many of them pathological. Even though the role of COX in homeostasis and disease in now well appreciated, controversial information is available concerning the distribution of COX isoforms in normal human tissues. There is mounting evidence that it is much more complex than generally believed. Our aim was therefore to analyse the expression and distribution of COX isoforms in normal human tissues, using immunohistochemistry, Western blotting and real‐time RT‐PCR. Autopsy samples from 20 healthy trauma victims and samples from 48 biopsy surgical specimens were included. COX‐1 was found in blood vessels, interstitial cells, smooth muscle cells, platelets and mesothelial cells. In contrast, COX‐2 was found predominantly in the parenchymal cells of many tissues, with few exceptions, for example the heart. Our results confirm the hypothesis that the distribution of COX isoforms in healthy tissues is much more complex than generally believed. This and previous studies indicate that both isoforms, not only COX‐1, are present in many normal human tissues, and that both isoforms, not only COX‐2, are up‐regulated in various pathological conditions. We may have to revise the concept of ‘constitutive’ and ‘inducible’ COX isoforms.

Association study of seven polymorphisms in four serotonin receptor genes on suicide victims

A number of molecular genetic studies have investigated if serotonin (5‐HT) receptor subtypes are involved in the pathogenesis of depression, suicidal behavior, aggression, and impulsive behavior. Existence of many receptor subtypes for a single transmitter permits a great diversity of signaling raising the possibility that they may serve as genetic markers for suicidal behavior. Most previous studies of suicide have analyzed polymorphisms of the receptors 5‐HT1A, 5‐HT1B, 5‐HT2A, fewer have examined 5‐HT1F. We report a study of possible association between the polymorphisms in the 5‐HT receptor genes (1A, 1B, 1F, and 2A) and suicidal behavior on a sample of 226 suicide victims and 225 healthy control subjects. No significant differences in genotype frequency distributions between the suicide victims and healthy control subjects were observed for four polymorphisms; three were not polymorphic. A single polymorphism, C‐1420T in gene 5‐HT2A, showed a slight association with suicide (χ2 = 4.94, df = 2, P = 0.067), but the correlation was not statistically significant. None of the tested genetic variants of serotonin receptors appears to be associated with suicidal behavior in the Slovenian population which has a relatively high suicide rate.

Investigating the associations between polymorphisms in the NTRK2 and NGFR genes and completed suicide in the Slovenian sample

Objective The most abundant neurotrophin in the mammalian brain is brain-derived neurotrophic factor (BDNF), which acts through binding to neurotrophic tyrosine kinase receptor type 2 (NTRK2) and to nerve growth factor receptor (NGFR). Our previous work showed an association of the single nucleotide polymorphism (SNP) rs6265 in the BDNF gene with completed suicide in the Slavic population. Therefore, we extended the investigation to the SNPs within NTRK2 and NGFR genes and searched for associations with the completed suicide phenotype. Materials and methods In 775 Caucasian individuals, namely, 486 suicide completers and 289 controls, we performed genotyping of five SNPs within the NTRK2 (rs11140714, rs1147198, rs1187323, rs10780691, and rs10868235) and six SNPs within the NGFR (rs2072446, rs7219709, rs7224806, rs734194, rs741071, and rs741072) genes. Results We did not find evidence for an association of the SNPs studied with the phenotype either on the single marker or on the haplotype level. Conclusion To our knowledge, this is the first study that has examined SNPs in the NTRK2 and NGFR genes for associations with the completed suicide phenotype. However, our findings suggest that these SNPs may not be associated particularly with completed suicide in Slovenia, although they might have a relevant informative value as the study has been carried out on a sample from a population that has one of the highest suicide rates in the world.