Monoamine oxidase A variants are associated with heavy betel quid use

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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 inhibitsMAO‐Aexpression and the role ofMAO‐Apolymorphisms 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 andMAO‐Aexpression in neuroblastoma SH‐SY5Y cells. After identifying the effective concentrations of arecoline and ANEin vitro, we examined thein vivoeffects of these compounds using a rat model system. Our results indicate that arecoline and ANE inhibitMAO‐Aexpression bothin vitroandin vivo. In addition, we examined the correlation between plasmaMAO‐Aactivity and cumulative exposure to BQ in humans. We recruited 1307 aborigines from a large‐scale community‐based survey to determine whetherMAO‐Avariants were associated with high BQ use and a preference for use with smoking or alcohol and whether gender bias existed.MAO‐Aexpression was significantly downregulated by arecoline and ANE at 100–200 µg/ml and in rat whole brains on days 30 and 45.MAO‐Aactivity 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 affectMAO‐Aenzymatic activity.

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