Comprehensive Analysis of ABCG2 Genetic Variation in the Polish Population and Its Inter-Population Comparison

Abstract

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 ABCG2 coding sequence in the Polish population. The genetic variation in 14 out of 15 coding exons of the ABCG2 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 ABCG2.

ABCG2 polymorphisms and susceptibility to ARV‐associated hepatotoxicity

“…Reduced expression of transporter protein is seen in several tissues as a result of the ABCG2 c.421 C/A polymorphism, which makes ABCG2 protein unstable, especially in the endoplasmic reticulum, thus increasing the vulnerability to denaturation (Furukawa et al, 2009;Kobayashi et al, 2005;Prasad et al, 2013;Tanaka et al, 2015). Our investigation found that the prevalence of the ABCG2 34G/A polymorphism in our healthy control group differed when compared with studies done by Bäckström et al (2003), Bosch et al (2005), however, it is comparable with studies conducted by Fischer et al (2007), Lee, Jeong, et al (2007), Słomka et al (2020), Wang et al (2004), Wang et al (2007). ABCG2 421AA and 34AA genotypes showed an elevated risk for advancement of HIV disease when patients with HIV infection were compared with healthy subjects (p = 0.49, OR: 2.49; p = 0.38, OR = 2.35).…”

Gene Variants Determine Placental Transfer of Perfluoroalkyl Substances (PFAS), Mercury (Hg) and Lead (Pb), and Birth Outcome: Findings From the UmMuKi Bratislava-Vienna Study

“…The amino acid substitution in the ALAD gene (Lys59Asn) leads to a more electronegative charge of the variant enzyme, which could alter binding affinities ( Onalaja and Claudio, 2000 ). The missense mutation of ABCG2 (Gln141Lys) is associated with reduced ABCG2 expression ( Slomka et al, 2020 ). The placental passage of PFOS and PFOA, however, has been shown to not depend on ABCG2 in a human placental perfusion model ( Kummu et al, 2015 ).…”