Association of polymorphisms in nicotinic acetylcholine receptor alpha 4 subunit gene (CHRNA4), mu-opioid receptor gene (OPRM1), and ethanol-metabolizing enzyme genes with alcoholism in Korean patients.
Findings obtained from several studies indicate that ethanol enhances the activity of alpha4beta2 neuronal nicotinic acetylcholine receptor and support the possibility that a polymorphism of the nicotinic acetylcholine receptor alpha4 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 mu-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.
Kim
Soon Ae
SA
Department of Pharmacology, Eulji University School of Medicine, 143-5 Yongdu-Dong, Jung-Gu, Daejeon, 301-832, Korea. sakim@eulji.ac.kr
Kim
Jong-Woo
JW
Song
Ji-Young
JY
Park
Sunny
S
Lee
Hee Jae
HJ
Chung
Joo-Ho
JH
D000328:Adult; D000368:Aged; D000426:Alcohol Dehydrogenase / Q000235:genetics / Q000378:metabolism; D000437:Alcoholism / Q000201:enzymology / Q000235:genetics*; D000444:Aldehyde Dehydrogenase / Q000235:genetics / Q000378:metabolism; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D044466:Asian People / Q000235:genetics*; D015252:Deoxyribonucleases, Type II Site-Specific / Q000235:genetics; D000431:Ethanol / Q000378:metabolism; D008040:Genetic Linkage / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011978:Receptors, Nicotinic / Q000235:genetics*; D017450:Receptors, Opioid, mu / Q000235:genetics*
D000426:Alcohol Dehydrogenase; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D015252:Deoxyribonucleases, Type II Site-Specific; D000431:Ethanol; D011978:Receptors, Nicotinic; D017450:Receptors, Opioid, mu; C485764:OPRM1 protein, human; C489332:ADH1B protein, human; C096127:ALDH2 protein, human; C037130:GCGC-specific type II deoxyribonucleases