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Odvisnost od alkohola je posledica okoljskih in genetskih dejavnikov. Na možganski center za nagrajevanje alkohol deluje posredno predvsem preko μ-opioidnega receptorja, ki ga v genomu kodira gen OPRM1. Tema naše raziskave je bilo iskanje vzročno-posledične povezave med odvisnostjo od alkohola in izraženostjo sopojavnih duševnih motenj (SDM) ter razporeditvijo genotipov polimorfizmov v genu OPRM1 v skupinah akutno odvisnih preiskovancev, abstinentnih preiskovancev in zdravih kontrol. Zanimalo nas je, ali se značilnosti preiskovancev in izraženost SDM med posameznimi skupinami statistično razlikujejo glede na razporeditev genotipov polimorfizmov OPRM1 rs1799971 in rs677830. Ker je genska ekspresija natančno uravnavana preko sistema molekul miRNA, smo v raziskavo vključili tudi dva polimorfizma genov za molekule miRNA, ki uravnavata izražanje gena OPRM1. To sta polimorfizem rs1011784 v genu MIR23B in polimorfizem rs2296616 v genu MIR107. Za oceno izraženosti sopojavne simptomatike smo uporabili ustrezne vprašalnike. Vzorce DNA smo analizirali z metodo KASP, na koncu pa je sledila še statistična analiza. Ugotovili smo, da alternativen alel T polimorfizma rs677830 poveča tveganje za pojav odvisnosti od alkohola ob upoštevanju stanu, starosti, izobrazbe in kajenja. Pri ostalih polimorfizmih nismo opazili vpliva na pojav odvisnosti od alkohola, smo pa opazili vpliv na izraženost SDM. Alel G polimorfizma rs1799971 je bil povezan z nižjo izraženostjo sovražnosti v skupini zdravih kontrol. Heterozigotiza ta polimorfizem v skupini abstinentnih preiskovancev so imeli večjo izraženost socialne anksioznosti. V skupini abstinentnih pacientov so imeli nosilci vsaj enega polimorfnega alela T polimorfizma rs677830 nižjo izraženost socialne anksioznosti. Referenčni alel G polimorfizma rs1011784 je bil pri akutno odvisnih pacientih povezan z višjo izraženostjo kompulzivnih in anksioznih simptomov. Največji vpliv na izraženost sopojavne simptomatike je imel polimorfizem rs2296616, pri katerem so nosilci vsaj enega polimorfnega alela A v skupini zdravih kontrol imeli višjo izraženost depresivne in anksiozne simptomatike, v skupini abstinentnih pacientov pa je bila bolj izražena anksiozna simptomatika pri homozigotih za referenčni alel G. V skupini zdravih kontrol smo opazili, da so nosilci vsaj enega polimorfnega alela A pogosteje uživali alkoholne pijače, vendar so bile razlike statistično značilne samo pri heterozigotih. Dobljeni rezultati bi nam lahko pomagali oceniti tveganje za izraženost SDM, kar bi povečalo uspešnost uspešnost z dravljenja odvisnosti. Alcohol dependence is caused by environmental and genetic factors. Alcohol acts indirectly on the brain's reward center, mainly via the μ-opioid receptor, which is encoded by the OPRM1 gene. Our study aimed to investigate the cause-effect relationship between alcohol dependence and the expression of co-occurring psychiatric disorders, and the genotype distribution of polymorphisms in the OPRM1 gene in groups of acutely dependent subjects, abstinent subjects, and healthy controls. We were interested in whether subjects differed statistically between groups and in the expression of co-occurring disorders with regard to the distribution of genotypes in the rs1799971 and rs677830 polymorphisms. Since gene expression is precisely regulated through the miRNA molecule system, two polymorphisms of the miRNA molecule genes regulating OPRM1 gene expression were also included in the study. These are the rs1011784 polymorphism in the MIR23B gene and the rs2296616 polymorphism in the MIR107 gene. The corresponding questionnaires were used to assess the expression of co-occurring disorders. DNA samples were analyzed by KASP, followed by statistical analysis. We found that the T allele of rs677830 polymorphism increased the risk of alcohol dependence when partnership, age, education, and smoking were also taken into account. For the other polymorphisms, we did not observe any effect on the occurrence of alcohol dependence, but we did observe an effect on the expression of comorbid symptomatology. The G allele of the rs1799971 polymorphism was associated with a lower expression of hostility in the group of healthy controls. Heterozygotes for this polymorphism in the abstinent group had a higher expression of social anxiety. In the abstinent group, carriers of at least one T allele of the rs677830 polymorphism had a lower expression of social anxiety. The reference G allele of the rs1011784 polymorphism was associated with a higher expression of compulsive and anxious symptoms in acutely dependent patients. The polymorphism rs2296616 had the greatest impact on the expression of comorbid symptomatology, with carriers of at least one polymorphic A allele in the healthy control group having a higher expression of depressive and anxiety symptoms. In the abstinent group, anxiety was expressed more in those homozygous for the reference G allele. In the healthy controls group, carriers of at least one polymorphic A allele were more likely to consume alcoholic beverages, but the differences were statistically significant only in heterozygotes. These results could help us assess the risk of co-occurring disorders, which would increase the success rate of addiction treatment. |
