title: Monoamine oxidase A variants are associated with heavy betel quid use.
abstract: Few studies have investigated whether genetic abnormalities predispose individuals to heavy betel quid (BQ) use. One of the major ingredients of BQ, arecoline, is known to affect the expression of monoamine oxidase A (MAO-A). We investigated the extent to which arecoline inhibits MAO-A expression and the role of MAO-A polymorphisms in BQ use in Taiwanese aborigines. Cytotoxicity assays, microarrays and quantitative reverse transcriptase-polymerase chain reaction were used to examine the effects of arecoline and areca nut extract (ANE) on cell viability and MAO-A expression in neuroblastoma SH-SY5Y cells. After identifying the effective concentrations of arecoline and ANE in vitro, we examined the in vivo effects of these compounds using a rat model system. Our results indicate that arecoline and ANE inhibit MAO-A expression both in vitro and in vivo. In addition, we examined the correlation between plasma MAO-A activity and cumulative exposure to BQ in humans. We recruited 1307 aborigines from a large-scale community-based survey to determine whether MAO-A variants were associated with high BQ use and a preference for use with smoking or alcohol and whether gender bias existed. MAO-A expression was significantly downregulated by arecoline and ANE at 100-200 µg/ml and in rat whole brains on days 30 and 45. MAO-A activity levels in human plasma were positively correlated with the extent of BQ exposure, and individuals with at-risk alleles exhibited lower activity, although this result did not reach statistical significance. We found two single nucleotide polymorphism (SNPs) in aboriginal males [rs2283725, odds ratio (OR) = 2.04; rs5953210, OR = 2.03] and females (rs2283725, OR = 1.54; rs5953210, OR = 1.59) that were associated with heavy BQ use. Those individuals carrying at-risk alleles who drank alcohol were twice as likely to be heavy BQ users. However, the effects of these SNPs on BQ use were significant even after controlling for alcohol use. Our results suggest that two specific loci may confer a susceptibility to BQ abuse and affect MAO-A enzymatic activity.
authors.affiliation: School of Dentistry, College of Dental Medicine, Department of Public Health and Environmental Medicine, Faculty of Medicine, Kaohsiung Medical University, Taiwan.
authors.forename: Ping-Ho
authors.initials: PH
authors.lastname: Chen
authors.forename: Hung-Pin
authors.initials: HP
authors.lastname: Tu
authors.forename: Shu-Jung
authors.initials: SJ
authors.lastname: Wang
authors.forename: Albert Min-Shan
authors.initials: AM
authors.lastname: Ko
authors.forename: Chi-Pin
authors.initials: CP
authors.lastname: Lee
authors.forename: Tai-An
authors.initials: TA
authors.lastname: Chiang
authors.forename: Yi-Shan
authors.initials: YS
authors.lastname: Tsai
authors.forename: Chien-Hung
authors.initials: CH
authors.lastname: Lee
authors.forename: Tien-Yu
authors.initials: TY
authors.lastname: Shieh
authors.forename: Chih-Hung
authors.initials: CH
authors.lastname: Ko
authors.forename: Shang-Lun
authors.initials: SL
authors.lastname: Chiang
authors.forename: Ying-Chin
authors.initials: YC
authors.lastname: Ko
mesh_terms: D000328:Adult; D000368:Aged; D000428:Alcohol Drinking / Q000378:metabolism; D000818:Animals; D001114:Areca; D001115:Arecoline / Q000494:pharmacology; D002470:Cell Survival; D002478:Cells, Cultured; D005260:Female; D056426:Genetic Loci / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D008995:Monoamine Oxidase / Q000235:genetics* / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D051381:Rats; D012907:Smoking / Q000378:metabolism; D019966:Substance-Related Disorders / Q000235:genetics*
chemical_list: D008996:Monoamine Oxidase Inhibitors; D001115:Arecoline; D008995:Monoamine Oxidase