背景:药物基因组学是个性化医疗的一个方面,它探索遗传变异如何影响药物代谢和药物不良反应。因此,本研究旨在检测景颇人群中不同的药物基因组变异,并探讨其与药物代谢和毒性的临床相关性。
方法:AgenaMassARRAY检测方法对来自159名无关景颇族参与者的28个基因中的57个VIP变异进行了基因分型。随后,利用卡方检验和Bonferroni的统计检验对景颇族与1000基因组计划的其他26个种群之间的基因型和等位基因频率进行了比较分析。
结果:我们发现KHV(何志明市的Kinh,越南),CHS(南汉汉语,中国)和JPT(东京的日语,日本)与景颇族的差异最小,只有4种变体,而ESN(尼日利亚的Esan)表现出最大的差异,有30个变体。此外,总共六个相当不同的基因座(ACE中的rs4291,本研究确定了PTGS2中的rs20417,NAT2中的rs1801280和rs1799929,ALOX5中的rs2115819,CYP2D6中的rs1065852,p<3.37×10-5)。根据PharmGKB的说法,rs20417(PTGS2),rs4291(ACE),发现rs2115819(ALOX5)和rs1065852(CYP2D6)与非甾体抗炎药(NSAIDs)的代谢效率有关,阿司匹林,孟鲁司特和他莫昔芬,分别。同时,发现rs1801280和rs1799929(NAT2)与缓慢乙酰化的药物中毒有关。
结论:我们的研究揭示了景颇人群中独特的药物基因组变异,并发现了它们与NSAIDs代谢效率的关联。孟鲁司特,还有他莫昔芬.
BACKGROUND: Pharmacogenomics is a facet of personalized medicine that explores how genetic variants affect drug metabolism and adverse drug reactions. Therefore, this study aims to detect distinct pharmacogenomic variations among the Jingpo population and explore their clinical correlation with drug metabolism and toxicity.
METHODS: Agena MassARRAY Assay was used to genotype 57 VIP variants in 28 genes from 159 unrelated Jingpo participants. Subsequently, the chi-squared test and Bonferroni\'s statistical tests were utilized to conduct a comparative analysis of genotypes and allele frequencies between the Jingpo population and the other 26 populations from the 1000 Genome Project.
RESULTS: We discovered that the KHV (Kinh in Ho ChiMinh City, Vietnam), CHS (Southern Han Chi-nese,
China) and JPT (Japanese in Tokyo, Japan) exhibited the smallest differences from the Jingpo with only 4 variants, while ESN (Esan in Nigeria) exhibited the largest differences with 30 variants. Besides, a total of six considerably different loci (rs4291 in ACE, rs20417 in PTGS2, rs1801280 and rs1799929 in NAT2, rs2115819 in ALOX5, rs1065852 in CYP2D6, p < 3.37 × 10-5) were identified in this study. According to PharmGKB, rs20417 (PTGS2), rs4291 (ACE), rs2115819 (ALOX5) and rs1065852 (CYP2D6) were found to be associated with the metabolism efficiency of non-steroidal anti-inflammatory drugs (NSAIDs), aspirin, montelukast and tamoxifen, respectively. Meanwhile, rs1801280 and rs1799929 (NAT2) were found to be related to drug poisoning with slow acetylation.
CONCLUSIONS: Our study unveils distinct pharmacogenomic variants in the Jingpo population and discovers their association with the metabolic efficiency of NSAIDs, montelukast, and tamoxifen.