1 Department of Pediatric Cardiology, West China Second University Hospital, Sichuan University , Chengdu, China .
DNA Cell Biol. 2014 Oct;33(10):689-98. doi: 10.1089/dna.2014.2398. Epub 2014 Jun 30.
Breast cancer resistance protein (BCRP) in the placenta, encoded by the ABCG2 gene in humans, plays an essential role in regulating fetal exposure to toxicants and the maintenance of cellular folic acid homeostasis. This study aimed at exploring the associations between 421C>A and 34G>A polymorphisms within the ABCG2 gene of the children and isolated septal defects in a Han Chinese population. An age- and gender-matched case-control study involving 210 pairs was conducted. Genotyping of the ABCG2 gene polymorphisms was performed by sequencing. Forty-six placental tissues and umbilical cords from healthy Han Chinese mothers with uncomplicated pregnancy were collected to investigate the impact of these two polymorphisms on the transcription and translation activities of the ABCG2 gene. The results showed that there were no differences in the genotype distributions and allele frequencies of 421C>A polymorphism. For the 34G>A polymorphism, more cases were carriers of the GA/AA genotypes (adjusted odds ratio [OR]: 1.6, 95% confidence interval [CI]: 1.0-2.3). The ABCG2 mRNA and protein expression did not differ among the three genotypes of 421C>A polymorphism. For the 34G>A polymorphism, the ABCG2 mRNA and protein expression of the GG genotype was significantly higher than that of the AA genotype. In conclusion, 34G>A polymorphism in the ABCG2 gene of the children is associated with isolated septal defects in a Han Chinese population, presumably through regulation of BCRP expression in the placenta.
胎盘中的乳腺癌耐药蛋白（BCRP）由人类 ABCG2 基因编码，在调节胎儿暴露于毒物和维持细胞叶酸内稳态方面发挥着重要作用。本研究旨在探讨 ABCG2 基因内 421C>A 和 34G>A 多态性与汉族儿童单纯性室间隔缺损之间的关系。进行了一项年龄和性别匹配的病例对照研究，共涉及 210 对。通过测序对 ABCG2 基因多态性进行基因分型。收集了 46 例来自汉族健康母亲的胎盘组织和脐带，这些母亲的妊娠均无并发症，以研究这两种多态性对 ABCG2 基因转录和翻译活性的影响。结果显示，421C>A 多态性的基因型分布和等位基因频率无差异。对于 34G>A 多态性，更多的病例是 GA/AA 基因型的携带者（调整后的比值比 [OR]：1.6，95%置信区间 [CI]：1.0-2.3）。421C>A 多态性的三种基因型之间，ABCG2 mRNA 和蛋白表达无差异。对于 34G>A 多态性，GG 基因型的 ABCG2 mRNA 和蛋白表达明显高于 AA 基因型。总之，儿童 ABCG2 基因中的 34G>A 多态性与汉族人群的单纯性室间隔缺损有关，可能是通过调节胎盘内 BCRP 的表达。
