Biobank Lab, Department of Molecular Biophysics, Faculty of Biology and Environmental Protection, University of Łódź, Pilarskiego 14/16, 90-231 Łódź, Poland.
BBMRI.pl Consortium, 54-066 Wrocław, Poland.
Genes (Basel). 2020 Sep 29;11(10):1144. doi: 10.3390/genes11101144.
ATP-binding cassette sub-family G member 2 (ABCG2), also known as breast cancer resistance protein (BCRP), is one of the key efflux ATP-binding cassette (ABC) transporters of xenobiotics, their metabolites and endogenous compounds such as urate. Some of its genetic variants have been found to influence protein functioning, resulting in serious clinical implications concerning chemotherapy response, as well as gout or blood group phenotype Jr(a-). Previous reports have suggested that the frequencies of certain crucial polymorphisms, such as c.34G>A (p.Val12Met) and c.421C>A (p.Gln141Lys) differ significantly between the Polish population and other Caucasian populations. Thus, to clarify this issue, the present study performs a complete analysis of the genetic variation of coding sequence in the Polish population. The genetic variation in 14 out of 15 coding exons of the gene, as well as their flanking intron sequences, were examined among 190 healthy representatives of the Polish population using scanning with High Resolution Melting (HRM). HRM scanning revealed 17 polymorphisms: eight in the exons (including five missense variants and one point-nonsense mutation) and nine in the intron sequences (eight single nucleotide polymorphisms (SNPs) and one deletion variant). These included variants correlating with the presence of gout and phenotype Jr(a-). Linkage disequilibrium, haplotype blocks and haplotype analyses were also performed. The frequencies of the most common polymorphisms in the Polish population did not differ significantly to those observed for other Caucasian populations, but demonstrated divergence from non-Caucasian populations. We hope that our findings may be helpful for other researchers and clinicians, evaluating the pharmacogenetic role of .
三磷酸腺苷结合盒亚家族 G 成员 2（ABCG2），也称为乳腺癌耐药蛋白（BCRP），是外源性物质、其代谢物和内源性化合物（如尿酸）的关键外排三磷酸腺苷结合盒（ABC）转运蛋白之一。已经发现其一些遗传变异会影响蛋白质功能，导致化疗反应、痛风或血型表型 Jr(a-)等严重的临床影响。先前的报告表明，某些关键多态性（如 c.34G>A（p.Val12Met）和 c.421C>A（p.Gln141Lys））的频率在波兰人群和其他白种人群之间存在显著差异。因此，为了澄清这个问题，本研究对波兰人群中编码序列的遗传变异进行了全面分析。使用高分辨率熔解（HRM）扫描，对 190 名波兰健康人群的 15 个外显子中的 14 个编码外显子及其侧翼内含子序列的遗传变异进行了检测。HRM 扫描发现了 17 个多态性：8 个在外显子中（包括 5 个错义变异和 1 个点无义突变），9 个在内含子序列中（8 个单核苷酸多态性（SNP）和 1 个缺失变异）。其中包括与痛风和 Jr(a-)表型存在相关的变异。还进行了连锁不平衡、单倍型块和单倍型分析。波兰人群中最常见的多态性频率与其他白种人群观察到的频率没有显著差异，但与非白种人群存在差异。我们希望我们的发现可以为其他研究人员和临床医生提供帮助，评估 的药物遗传学作用。
