Jarrar Yazun Bashir, Balasmeh Ayat Ahmed, Jarrar Wassan
a Department of Pharmacy, College of Pharmacy , AlZaytoonah University of Jordan , Amman , Jordan.
Libyan J Med. 2018 Dec;13(1):1408381. doi: 10.1080/19932820.2017.1408381.
The present study aimed to identify the NAT2 haplotypes, linkage disequilibrium, and novel NAT2 genetic variants among Jordanian population. We isolated the genomic DNA from 68 healthy, Arab, unrelated Jordanian volunteers to amplify the protein-coding region of NAT2 gene by polymerase chain reaction (PCR). Then, the amplified PCR products were sequenced using Applied Biosystems Model (ABI3730x1). It is found that the allele frequencies of known NAT2 genetic variants 191G>A, 282C>T, 341T>C, 481C>T, 590G>A, and 803A>G were 0.7, 26.5, 48.5, 35.3, 30.9, and 32.4%, respectively. The NAT2 allele frequencies were generally similar to those of white Europeans but different from those of Asian and African populations. The most common NAT2 haplotype was NAT25B with a frequency of 29.3%. According to the NAT2 haplotype frequencies, 72% (95% confidence interval 61.4-82.7%) of the volunteers were slow encoding NAT2 haplotype acetylators. The NAT25 represented variants 341T>C and 481C>T were in strong but not complete linkage disequilibrium (D' = 0.8, r = 0.63). In addition, this study found a novel nonsynonymous NAT2 436G>A genetic variant with low frequency (0.7%). However, this novel variant was predicted to be tolerated and not harmful to the NAT2 protein, using in silico prediction tools. It is concluded that the frequency of slow encoding NAT2 haplotype was high among Jordanian volunteers, which may have effects on drug responses and susceptibility to some diseases, such as cancers.
本研究旨在鉴定约旦人群中的NAT2单倍型、连锁不平衡及新的NAT2基因变异。我们从68名健康、阿拉伯裔、无亲缘关系的约旦志愿者中分离基因组DNA，通过聚合酶链反应（PCR）扩增NAT2基因的蛋白质编码区。然后，使用应用生物系统公司的ABI3730x1型号对扩增的PCR产物进行测序。结果发现，已知的NAT2基因变异191G>A、282C>T、341T>C、481C>T、590G>A和803A>G的等位基因频率分别为0.7%、26.5%、48.5%、35.3%、30.9%和32.4%。NAT2等位基因频率总体上与欧洲白人相似，但与亚洲和非洲人群不同。最常见的NAT2单倍型是NAT25B，频率为29.3%。根据NAT2单倍型频率，72%（95%置信区间61.4 - 82.7%）的志愿者为慢乙酰化编码NAT2单倍型。代表变异341T>C和481C>T的NAT25处于强但不完全的连锁不平衡状态（D' = 0.8，r = 0.63）。此外，本研究发现了一个低频（0.7%）的新的非同义NAT2 436G>A基因变异。然而，使用计算机预测工具预测该新变异对NAT2蛋白具有耐受性且无害。结论是，约旦志愿者中慢乙酰化编码NAT2单倍型的频率较高，这可能对药物反应及某些疾病如癌症的易感性产生影响。
