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在巴西亚马逊地区的三个不同的土著种群中发现NUDT15和TPMT多态

Jamila Alessandra Perini¹, Paulo Cesar Basta², Guilherme Suarez-Kurtz³

¹Laboratório de Pesquisa de Ciências Farmacêuticas (LAPESF), Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro, Brazil.

Frontiers in pharmacology

|February 21, 2024

概括

在TPMT和NUDT15的遗传变异影响了硫氨酸药物代谢. 巴西亚马逊地区的Paiter-Suruí土著群体显示出这些变异的频率明显更高,增加了他们患氨酸不耐受症的风险.

科学领域:

药物遗传学药物遗传学
人口遗传学人口遗传学
临床药理学临床药理学

背景情况:

提奥普林药物广泛用于治疗各种疾病,包括自身免疫性疾病和癌症.
氨酸S-甲基转移酶 (TPMT) 和核酸二酸链接转基因15 (NUDT15) 的遗传变异影响了氨酸药物代谢和毒性.
了解这些遗传变异在不同人群中的分布对于个性化医学至关重要.

研究的目的:

调查TPMT和NUDT15单核酸多态 (SNPs) 和相关代谢表型在亚马逊土著群体的分布:蒙杜鲁库,Paiter-Suruí和Yanomami.
评估这些基因变异对这些群体中氨酸药物反应和毒性风险的药物遗传学影响.

主要方法:

使用已确定的基因型化技术对TPMT (rs1800460,rs1142345) 和NUDT15 (rs116855232) SNPs进行基因型化.
对小等位基频率 (MAF) 和TPMTSNP之间的链接不平衡的分析.
结合NUDT15/TPMT代谢表型的确定和对三个土著群体进行比较.

主要成果:

NUDT15 rs116855232的MAF在各组之间没有显著差异.
所有研究组中都没有TPMT rs1800462.
TPMT rs1800460和rs1142345存在强烈的链接不平衡,在Paiter-Suruí中明显更常见 (MAF分别为0.193和0.188),代表了全球报告的最高频率.
组合的NUDT15/TPMT代谢表型的分布在整个队列中有显著差异 (p < 0.0001).
药物遗传学影响:41%的Paiter-Suruí个人,相比之下,4.4%的Yanomami和5.6%的Munduruku,建议根据临床药物遗传学实施联盟的指导方针减少蒂奥普林剂量.
皮特-苏鲁伊人群的皮素不耐受风险比全球其他受研究的人群高3至4倍.

结论:

在亚马逊土著人口中,TPMT和NUDT15遗传特征存在显著的种族间差异.
在Paiter-Suruí群体中,TPMT变异的流行率很高,导致硫氨酸诱导毒性的风险大幅增加.
这些发现强调了对特定人群的药物遗传查的关键需求,以确保巴西亚马逊地区的安全和有效的氨酸治疗.

关键词:

巴西亚马逊 - 巴西亚马逊在 NUDT1515 中.在TPMTTTTTTT 遗传多形态主义是一种遗传多形态主义.本地祖先的原住民血统.药物遗传学药物遗传学人口的多样性人口的多样性这种药物是 thiopurine.

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