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首页> 外文期刊>Addiction biology >Monoamine oxidase a variants are associated with heavy betel quid use
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Monoamine oxidase a variants are associated with heavy betel quid use

机译：单胺氧化酶a变体与大量槟榔使用有关

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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.
机译：很少有研究调查遗传异常是否使个体容易使用大量槟榔（BQ）。已知BQ的主要成分之一槟榔碱会影响单胺氧化酶A（MAO-A）的表达。我们调查了槟榔碱抑制MAO-A表达的程度以及台湾原住民在BQ使用中MAO-A多态性的作用。细胞毒性试验，微阵列和定量逆转录酶-聚合酶链反应用于检查槟榔碱和槟榔提取物（ANE）对神经母细胞瘤SH-SY5Y细胞活力和MAO-A表达的影响。在确定了槟榔碱和ANE的有效浓度后，我们使用大鼠模型系统检查了这些化合物的体内作用。我们的结果表明槟榔碱和ANE在体外和体内均抑制MAO-A表达。此外，我们检查了血浆中MAO-A活性与人体BQ累积暴露之间的相关性。我们从一项基于社区的大规模调查中招募了1307名土著居民，以确定MAO-A变体是否与高BQ使用率相关联，是否倾向于吸烟或酗酒以及是否存在性别偏见。在第30和45天，槟榔碱和ANE在100-200μg/ ml以及大鼠全脑中均显着下调了MAO-A的表达。人血浆中MAO-A的活性水平与BQ暴露程度呈正相关，具有高风险等位基因的人表现出较低的活性，尽管该结果未达到统计学意义。我们在原住民男性中发现了两个单核苷酸多态性（SNPs）[rs2283725，优势比（OR）= 2.04; rs5953210，OR = 2.03]和女性（rs2283725，OR = 1.54; rs5953210，OR = 1.59）与大量使用BQ有关。那些携带高风险等位基因的人喝酒的可能性是BQ使用者的两倍。但是，即使控制酒精使用后，这些SNP对BQ使用的影响也很明显。我们的结果表明，两个特定的基因座可能会导致滥用BQ并影响MAO-A的酶活性。

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