Genes and alcohol use: effects of common genetic polymorphisms in general population

Abstract

Alkoholi kuritarvitamine on üks peamistest ennetatavate surmade ja terviserikete põhjustajatest. Lähtuvalt sellest, kui palju probleeme tekib tarvitajale endale ja teda ümbritsevatele, on alkohol loetud kõige kahjulikumaks uimastiks1. Kuigi olukord on tasapisi paranemas, paistab Eesti rahvusvahelisel tasandil veel jätkuvalt silma ohtra alkoholitarbimisega2. Mehed tarvitavad alkoholi ning kogevad alkoholiga seotud probleeme enamasti rohkem kui naised. Nii ka meie rahvastikupõhises pikaajalises sünnikohortide uuringus – poisid alustasid alkoholi tarvitamisega varem ning tegelesid sellega sagedamini kui tüdrukud. Nooreks täiskasvanueaks oli selle tulemusena meeste seas tunduvalt rohkem neid, kes alkoholi kuritarvitamisega hädas. Alkoholiprobleemide kogemise tõenäosust tõstsid ka stressirikkad elusündmused ning halvad suhted pereliikmete ja õpetajatega. Kuna alkoholism on krooniline ja ravile raskesti alluv, on selle haiguse tekkimist ennustavate bioloogiliste näitajate uurimine äärmiselt päevakajaline. Analüüsides geenide mõju alkoholitarbimisele, leidsime, et probleemset alkoholitarbimist ennustasid just sellised geneetilised eripärad, mis olid seotud madalama stressitaluvuse ja suurema avatusega keskkondlike mõjude suhtes. Seosed ei olnud aga üleüldised ja sõltusid suures osas sünnikohordist – perioodist, mil inimene sündinud oli. Sotsiaalsed normid ja hoiakud alkoholi tarbimisse koonduvad sünnikohortide kaupa ning mõjutavad otseselt uimastite tarvitamist. 1990. aastatel alguse saanud kiired ühiskondlikud muutused mõjutavad meie siirdeühiskonnas väärtushinnanguid, vaba aja tegevusi, suhteid ja igapäevast toimetulekut. Kultuurilised ja ühiskondlikud muutused vormivad pidevalt inimeste identiteeti ja elustiili ning võivad vahendada ka geeniefekte alkoholitarbimisele. [1 Nutt DJ, King LA, Phillips LD (2010) Drug harms in the UK: a multicriteria decision analysis. Lancet 376:1558-1565. 2 OECD (2015) Tackling harmful alcohol use: Economics and public health policy. OECD Publishing.]

Problematic use of alcohol is one of the leading causes of preventable deaths and disability. Based on the harm to the user and others, alcohol has been considered to be the most harmful drug1. Men generally drink more alcohol and have more alcohol-related problems than women. Also in our population-representative longitudinal birth cohort study in Estonia, the boys started consuming alcohol earlier and were more frequent alcohol consumers than girls. By young adulthood, there were significantly more men than women diagnosed with alcohol use disorder. The more frequent was the alcohol consumption during the teenage years, the more problable was the occurrence of alcohol problems by young adulthood. In addition, the more stressful life events, the worse relationships with family members and with teachers the children experienced, the higher was the likelihood of developing alcohol use problems later on in life. The chronic nature of alcoholism is the reason why the search for predictive biomarkers is so urgent. When we analyzed the effects of common genetic variances on alcohol use and abuse, the genotypes associated with higher levels of stress reactivity and openness to environmental influences were the ones also linked to problematic alcohol use. However, the relations were not universal and strongly depended on birth cohort – the time period when one was born. Social norms and attitudes regarding alcohol use cluster in birth cohorts, and this clustering has a direct effect on drug use. The rapid socioeconomic changes that have taken place in Estonia since the beginning of 1990s and are still ongoing affect the values, activities, relationships, leisure time choices and everyday functioning of the people living in this transition society. Cultural transformation processes continuously shape the identities and lifestyles of individuals, and can also moderate the genetic effects on alcohol consumption. [1 Nutt DJ, King LA, Phillips LD (2010) Drug harms in the UK: a multicriteria decision analysis. Lancet 376:1558-1565.]