Shakibi Reyhaneh, Kamalidehghan Behnam, Ahmadipour Fatemeh, Meng Goh Yong, Houshmand Massoud
Department of Molecular and Cellular Sciences, Faculty of Advanced Sciences and Technology, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran.
Chemotherapy. 2014;60(5-6):279-87. doi: 10.1159/000376568. Epub 2015 May 9.
Pharmacogenetic studies on irinotecan treatment in patients with metastatic colorectal cancer have indicated that genetic polymorphisms in UGT1A16 can lead to decreased enzyme activity and accumulation of the toxic metabolite SN-38. Here, we compared the prevalence of UGT1A16 in an Iranian population of different ethnicities with those of other populations.
A total of 300 healthy people of different ethnic groups including Persian, Azari, Lure, Kurdish, Arab, Baluch and Caspian in the Iranian population were enrolled. Genotyping of the UGT1A1*6 alleles (G/G, A/G, A/A) was performed by polymerase chain reaction-restriction fragment length polymorphism and direct genomic DNA sequencing.
The most predictive genotype among the Iranian ethnic groups, especially Persian, was the G/G genotype (wild-type genotype). The frequency of the A/G genotype among the Persian, Azari, Lure, Kurdish, Arab, Baluch and Caspian ethnicities were 15.69% (n = 27), 11.11% (n = 8), 5.88% (n = 1), 9.09% (n = 1), 10% (n = 1), 20% (n = 1) and 0% (n = 0), respectively. Only one person with Persian ethnicity was homozygous for the mutation in UGT1A1*6 (0.58%). Additionally, the frequency of the A and G alleles in Iranians was 6.83 and 93.16%, respectively.
The identification of the UGT1A1*6 alleles is necessary among the different Iranian ethnic groups before irinotecan therapy, suggesting that genotyping would be helpful for clinicians to optimize chemotherapy or identify individuals at risk of adverse drug reactions before clinical trials.
针对转移性结直肠癌患者进行的伊立替康治疗的药物遗传学研究表明，UGT1A16基因多态性可导致酶活性降低以及毒性代谢物SN-38的蓄积。在此，我们比较了伊朗不同种族人群中UGT1A16的流行率与其他人群的流行率。
纳入了伊朗人群中300名不同种族的健康人，包括波斯人、阿扎里人、卢尔人、库尔德人、阿拉伯人、俾路支人和里海人。通过聚合酶链反应-限制性片段长度多态性和直接基因组DNA测序对UGT1A1*6等位基因（G/G、A/G、A/A）进行基因分型。
在伊朗各民族中，尤其是波斯人中，最具预测性的基因型是G/G基因型（野生型基因型）。波斯人、阿扎里人、卢尔人、库尔德人、阿拉伯人、俾路支人和里海人种族中A/G基因型的频率分别为15.69%（n = 27）、11.11%（n = 8）、5.88%（n = 1）、9.09%（n = 1）、10%（n = 1）、20%（n = 1）和0%（n = 0）。只有一名波斯族个体为UGT1A1*6突变纯合子（0.58%）。此外，伊朗人中A和G等位基因的频率分别为6.83%和93.16%。
在伊立替康治疗前，有必要在不同伊朗种族中鉴定UGT1A1*6等位基因，这表明基因分型有助于临床医生优化化疗方案或在临床试验前识别有药物不良反应风险的个体。
