Association of polymorphisms in nicotinic acetylcholine receptor α₄ subunit gene (CHRNA4), μ-opioid receptor gene (OPRM1), and ethanol-metabolizing enzyme genes with alcoholism in Korean patients

Abstract 

Findings obtained from several studies indicate that ethanol enhances the activity of α₄β₂ neuronal nicotinic acetylcholine receptor and support the possibility that a polymorphism of the nicotinic acetylcholine receptor α₄ subunit gene (CHRNA4) modulates enhancement of nicotinic receptor function by ethanol. To identify the association between the CfoI polymorphism of the CHRNA4 and alcoholism, we examined distribution of genotypes and allele frequencies in Korean patients diagnosed with alcoholism (n=127) and Korean control subjects without alcoholism (n=185) with polymerase chain reaction–restriction fragment length polymorphism methods. We were able to detect the association between the CfoI polymorphism of the CHRNA4 and alcoholism in Korean patients (genotype P=.023; allele frequency P=.047). The genotypes and allele frequencies of known polymorphisms in other alcoholism candidate genes, such as alcohol metabolism–related genes [alcohol dehydrogenase 2 (ADH2), aldehyde dehydrogenase 2 (ALDH2), alcohol dehydrogenase 3 (ADH3), and cytochrome P450 2E1 (CYP2E1)] and μ-opioid receptor gene (OPRM1), were studied. The polymorphisms of ADH2, ALDH2, and CYP2E1 were significantly different in Korean patients with alcoholism and Korean control subjects without alcoholism, but ADH3 and OPRM1 did not differ between the two groups.

Keywords: Nicotinic acetylcholine receptor α₄ subunit gene (CHRNA4), Alcoholism, Polymorphism, μ-opioid receptor gene (OPRM1), Alcohol dehydrogenase (ADH), Aldehyde dehydrogenase (ALDH), Cytochrome P450 2E1 (CYP2E1)