Botton Mariana Rodrigues, Hentschke-Lopes Marina, Matte Ursula
Department of Genetics, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
Cells, Tissues and Genes Laboratory, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil.
Ann Hum Genet. 2022 Mar;86(2):102-107. doi: 10.1111/ahg.12453. Epub 2021 Dec 13.
Fluoropyrimidines are chemotherapy drugs that may cause severe adverse events, and their metabolism occurs by dihydropyrimidine deydrogenase (DPD), coded by DPYD. Variants in the DPYD were associated to a greater risk of toxicity. Our aim was to determine the frequency of the most relevant DPYD alleles according to CPIC guidelines (DPYD2A-rs3918290, DPYD13-rs55886062, rs67376798, and HapB3-rs75017182) in a sample of 800 healthy Southern Brazilians. Frequencies for rs3918290, rs75017182, and rs67376798 were 0.25%, 1.06%, and 0.38%, respectively. No rs55886062 allele was detected. In total, 3.4% of individuals were classified as intermediate metabolizers. Frequencies for rs3918290, rs55886062, and rs67376798 were similar to those found in non-Finnish Europeans; however, rs75017182 was less frequent when compared to non-Finnish Europeans, but more frequent than in Africans and East Asians. rs3918290 and rs67376798 also presented higher frequency when compared to Africans. The Latino population was the only one that did not differ from our sample in any variant analyzed. The frequencies for all the other populations (non-Finnish European, African, South Asian, and East Asian) presented differences from our sample in at least one variant. rs115232898 was not analyzed in the present study. Cost-effective studies should be performed to evaluate the implementation of these tests in the clinical practice in the Southern Brazil.
氟嘧啶是可能导致严重不良事件的化疗药物，其代谢由二氢嘧啶脱氢酶（DPD，由DPYD编码）进行。DPYD基因变异与更高的毒性风险相关。我们的目的是根据CPIC指南（DPYD2A-rs3918290、DPYD13-rs55886062、rs67376798和HapB3-rs75017182），在800名巴西南部健康人群样本中确定最相关的DPYD等位基因频率。rs3918290、rs75017182和rs67376798的频率分别为0.25%、1.06%和0.38%。未检测到rs55886062等位基因。总体而言，3.4%的个体被归类为中间代谢者。rs3918290、rs55886062和rs67376798的频率与在非芬兰欧洲人中发现的频率相似；然而，与非芬兰欧洲人相比，rs75017182的频率较低，但比非洲人和东亚人更常见。与非洲人相比，rs3918290和rs67376798也表现出更高的频率。拉丁裔人群是在任何分析的变异中与我们的样本没有差异的唯一群体。所有其他人群（非芬兰欧洲人、非洲人、南亚人和东亚人）的频率在至少一个变异中与我们的样本存在差异。本研究未分析rs115232898。应进行成本效益研究，以评估在巴西南部临床实践中实施这些检测的情况。
