Functional polymorphism of neuronal tryptophan hydroxylase gene in conditions with disturbed serotonergic transmission

Serotonin je neurotransmiter uključen u regulaciju brojnih fizioloških funkcija i etiopatogenezu različitih neuropsihijatrijskih poremećaja. TPH2 (neuronska triptofan hidroksilaza) katalizira prvi korak u sintezi moždanog serotonina. Ujedno je to i korak koji ograničava brzinu cijelog anaboličkog puta pa polimorfizmi gena za ovaj enzim mogu utjecati na razinu serotonina u mozgu. U ovom radu istraživan je utjecaj funkcionalnog polimorfizma rs4290270 gena za TPH2 na razvoj suicidalnog ponašanja, alkoholizma, autizma, migrene i epilepsije temporalnog režnja usporedbom distribucije alela i genotipova između skupine zdravih ispitanika i skupine oboljelih osoba. U muškoj populaciji pronađena je značajna povezanost polimorfizma rs4290270 s alkoholizmom tipa 2, te indikativna povezanost s alkoholizmom tipa 1 i suicidalnim ponašanjem. U slučaju autizma, migrene i epilepsije temporalnog režnja, rezultati nisu pokazali povezanost, ali zbog određenih nedostataka, bilo bi poželjno ponoviti istraživanje s više ispitanika.Serotonin is neurotransmitter involved in the regulation of numerous physiological functions and in the etiopathogenesis of various neuropsychiatric conditions. TPH2 (neuronal tryptophan hydroxylase) catalyses the fist, rate-limiting step of brain serotonin synthesis so polymorphisms within the gene for TPH2 can affect overall serotonin levels in the central nervous system. The present work investigated the influence of rs4290270 polymorphism on the development of suicidal behavior, alcoholism, autism, migraine and temporal lobe epilepsy, by comparing allele and genotype distributions between case and control samples. rs4290270 polymorphism displayed significant association with alcoholism type 2 and indicative association with alcoholism type 1 and suicidal behavior in a male population. In cases of autism, migraine and temporal lobe epilepsy no associations were found, but due to certain limitations, it is recommended to repeat the study with more subjects