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.

Sinulariolide Inhibits Gastric Cancer Cell Migration and Invasion through Downregulation of the EMT Process and Suppression of FAK/PI3K/AKT/mTOR and MAPKs Signaling Pathways

“…Snail is one of the most important molecules in the EMT process; it binds to the E-box region of the E-cadherin promoter, directly inhibiting E-cadherin DNA transcription, reducing its protein expression, and promoting EMT [53]. Snail also affects the ability of cancer cells to invade the surrounding tissue [54]. In the EMT process, loss of cell adhesion ability is accompanied by changes in molecular type, including decreased expressions of structural proteins in epithelial cells and increased expressions of structural proteins in mesenchymal cells.…”

Antidepressants in association with reducing risk of oral cancer occurrence: a nationwide population-based cohort and nested case-control studies

“…The attributable fraction, combined from alcohol, BQ, and cigarette use, to cancers of the pharynx and larynx were 93% [ 43 ]. The antidepressant properties of BQ and arecoline have been reported to directly inhibit MAO-A enzymatic activity in cell, rat, and human models [ 44 – 47 ]. MAO-A metabolizes various primary, secondary, and tertiary monoamines and preferentially deaminates neurotransmitters relative to depression.…”

Betel‐quid dependence domains and syndrome associated with betel‐quid ingredients among chewers: anAsian multi‐country evidence

“…BQ-D is a multi-faceted factor contributing to sustained BQ consumption, and is a principal syndrome associated with clinical managements of chewers. Understanding the association of BQ ingredients and practice behaviour with BQ-D symptoms and syndrome, as well as related genetic susceptibility [40], may enable the development of clinical therapy for addiction cessation.…”