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中华妇幼临床医学杂志(电子版) ›› 2014, Vol. 10 ›› Issue (03) : 290 -295. doi: 10.3877/cma.j.issn.1673-5250.2014.03.006

所属专题: 文献

论著

基因多态性对人胎盘ABCG2基因mRNA及其蛋白表达的影响
李华英1, 王川2, 周开宇3, 刘兴会4, 谢亮5, 华益民6,*,*()   
  1. 1. 610041 成都,四川大学华西第二医院儿科心血管科
    2. 610041 成都,四川大学华西第二医院儿科心血管科 四川大学华西临床医学院
    3. 610041 成都,四川大学华西第二医院儿科心血管科 长江学者和创新团队发展计划
    4. 610041 成都,四川大学华西第二医院产科
    5. 610041 成都,四川大学华西第二医院肺血管重构实验室 长江学者和创新团队发展计划
    6. 610041 成都,四川大学华西第二医院儿科心血管科 610041 成都,四川大学华西第二医院肺血管重构实验室 长江学者和创新团队发展计划
  • 收稿日期:2014-01-09 修回日期:2014-04-04 出版日期:2014-06-01
  • 通信作者: 华益民

Effects of Genetic Polymorphisms on the Expression of mRNA and Protein of ABCG2 Gene in Human Placenta

Huaying Li1, Chuan Wang2, Kaiyu Zhou3, Xinghui Liu4, Liang Xie5, Yimin Hua6()   

  1. 1. Department of Pediatric Cardiovascular Disease, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
  • Received:2014-01-09 Revised:2014-04-04 Published:2014-06-01
  • Corresponding author: Yimin Hua
  • About author:
    (Corresponding author: Hua Yimin, Email: )
引用本文:

李华英, 王川, 周开宇, 刘兴会, 谢亮, 华益民. 基因多态性对人胎盘ABCG2基因mRNA及其蛋白表达的影响[J/OL]. 中华妇幼临床医学杂志(电子版), 2014, 10(03): 290-295.

Huaying Li, Chuan Wang, Kaiyu Zhou, Xinghui Liu, Liang Xie, Yimin Hua. Effects of Genetic Polymorphisms on the Expression of mRNA and Protein of ABCG2 Gene in Human Placenta[J/OL]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2014, 10(03): 290-295.

目的

评估单核苷酸多态位点对人胎盘ABCG2基因mRNA及蛋白表达的影响。

方法

选择2013年3月至5月在四川大学华西第二医院产科待产分娩的46例汉族正常孕产妇及新生儿为研究对象,收集其胎盘及脐带标本(本研究遵循的程序符合四川大学华西第二医院人体试验委员会制定的伦理学标准,得到该委员会批准,获得胎盘及脐带标本时均取得产妇及家属的知情同意,并与之签署临床研究知情同意书)。其中,脐带标本用于胎儿DNA的提取,胎盘标本用于ABCG2基因的RNA及蛋白提取;通过测序确定ABCG2基因421C>A及34G>A多态位点的基因型;分别通过实时荧光定量(RT)-PCR及Western-blotting法获得ABCG2基因的mRNA及蛋白表达情况。对ABCG2基因421C>A及34G>A多态位点不同基因型之间mRNA及蛋白相对表达量进行比较。ABCG2基因421C>A及34G>A多态位点不同基因型之间孕产妇及新生儿一般临床资料比较,差异均无统计学意义(P>0.05)。

结果

对于421C>A多态位点,携带CC、CA、AA各基因型的胎盘标本的平均mRNA及蛋白表达水平比较,其差异均无统计学意义(F=1.060,3.051;P>0.05);对于34G>A多态位点,携带GG基因型的胎盘标本平均mRNA及蛋白表达水平较携带AA基因型的胎盘标本高,且差异均有统计学意(q=3.540,4.720;P<0.05),而携带GA基因型的胎盘标本,其平均mRNA及蛋白表达水平分别与携带其他2种基因型的胎盘标本比较,其差异均无统计学意义(P>0.05)。

结论

421C>A多态位点对人胎盘ABCG2基因mRNA及蛋白的表达无影响,而34G>A多态位点对人胎盘ABCG2基因mRNA及ABCG2蛋白(BCRP)的表达均有影响。

Objective

To evaluate the effects of mononucleotide polymorphisms on the mRNA and protein expression of ABCG2 gene in human placenta.

Methods

From March to May 2013, a total of 46 healthy Han Chinese pregnant women and their newborns were selected as study subjects from the Department of Obstetrics and Gynecology in West China Second University Hospital, Sichuan University.Their placentas and umbilical cords were consecutively collected.The study protocol was approved by the Ethical Review Board of Investigation in Human Being of West China Second University Hospital, Sichuan University.Informed consents were obtained from all participants.Fetal DNA were extracted from the umbilical cords, RNA and protein of ABCG2 gene were extracted from the placental tissue.Genotypes of the ABCG2 gene 421C>A and 34G>A polymorphism were performed by sequencing.The expression of ABCG2 gene mRNA and protein in the placenta were determined by real time(RT)-PCR and Western-blotting. The comparisons of mRNA and protein expression were performed among different genotypes of 421C>A and 34G>A polymorphism of ABCG2 gene.The general clinical data of pregnant women and neonates among different genotypes had no significant differences (P>0.05).

Results

The mean ABCG2 gene mRNA and protein expression had no significant differences among CC, CA and AA genotypes of 421C>A polymorphism (F=1.060, 3.051; P>0.05); however, for 34G>A polymorphism, the mean ABCG2 gene mRNA and protein expression of GG genotype were significantly higher than those of AA genotype(q=3.540, 4.720; P<0.05), while for the samples carrying GA genotype, had no significant difference compared with other two genotypes(P>0.05), respectively.

Conclusions

The 421C>A polymorphism has no impacted on the expression of mRNA and protein of the ABCG2 gene in human placenta, while the 34G>A polymorphism has effected on both of them.

表1 ABCG2基因421C>A不同基因型之间孕产妇及新生儿一般临床资料比较(±s)
Table 1 Comparison of maternal and neonatal general clinical data among different genotypes of 421C>A polymorphism in ABCG2 gene(±s)
表2 ABCG2基因34G>A不同基因型之间孕产妇及新生儿一般临床资料比较(±s)
Table 2 Comparison of maternal and neonatal general clinical data among different genotypes of 34G>A polymorphism in ABCG2 gene(±s)
表3 ABCG2基因421C>A不同基因型之间mRNA及蛋白相对表达量比较(±s)
Table 3 Comparison of relative expressions of mRNA and protein among different genotypes of 421C>A polymorphism in ABCG2 gene(±s)
表4 ABCG2基因34G>A不同基因型之间mRNA及蛋白相对表达量比较(±s)
Table 4 Comparison of relative expressions of mRNA and protein among different genotypes of 34G>A polymorphism in ABCG2 gene(±s)
图1 ABCG2基因421C>A及34G>A位点不同基因型mRNA相对表达量
Figure 1 The relative expression of mRNA among different genotypes of 421C>A and 34G>A polymorphism in ABCG2 gene
图2 ABCG2基因421C>A及34G>A位点不同基因型BCRP相对表达量
Figure 2 The relative expression of BCRP among different genotypes of 421C>A and 34G>A polymorphism in ABCG2 gene
1
Doyle LA, Yang W, Abruzzo LV, et al. A multidrug resistance transporter from human MCF-7 breast cancer cells[J].Proc Natl Acad Sci USA, 1998, 95(26):15665-15670.
2
Staud F, Pavek P. Breast cancer resistance protein (BCRP/ABCG2)[J]. Int J Biochem Cell Biol, 2005, 37(4):720-725.
3
Xu J, Liu Y, Yang Y, et al.Characterization of oligomeric human half-ABC transporter ATP-binding cassette G2[J].J Biol Chem, 2004, 279(19):19781-19789.
4
Andrade SE, Gurwitz JH, Davis RL, et al. Prescription drug use in pregnancy[J]. Am J Obstet Gynecol, 2004, 191(2):398-407.
5
Ito S. Transplacental treatment of fetal tachycardia: implications of drug transporting proteins in placenta[J]. Semin Perinatol, 2001, 25(3):196-201.
6
Oudijk MA, Ruskamp JM, Ambachtsheer BE, et al. Drug treatment of fetal tachycardias[J]. Paediatr Drugs, 2002, 4(1):49-63.
7
Jonker JW, Smit JW, Brinkhuis RF, et al. Role of breast cancer resistance protein in the bioavailability and fetal penetration of topotecan[J]. J Natl Cancer Inst, 2000, 92(20):1651-1656.
8
Jonker JW, Buitelaar M, Wagenaar E, et al. The breast cancer resistance protein protects against a major chlorophyll-derived dietary photo toxin and protoporphyria[J]. Proc Natl Acad Sci USA, 2002, 99(24):15649-15654.
9
Cygalova L, Ceckova M, Pavek P, et al. Role of breast cancer resistance protein (BCRP/ABCG2) in fetal protection during gestation in rat[J]. Toxicol Lett, 2008, 178(3):176-180.
10
Pollex E, Lubetsky A, Koren G. The role of placental breast cancer resistance protein in the efflux of glyburide across the human placenta[J]. Placenta, 2008, 29(8):743-747.
11
Gedeon C, Anger G, Piquette-Miller M, et al. Breast cancer resistance protein: mediating the trans-placental transfer of glyburide across the human placenta[J]. Placenta, 2008, 29(1):39-43.
12
Zhou L, Naraharisetti SB, Wang H, et al. The breast cancer resistance protein (BCRP1/ABCG2) limits fetal distribution of glyburide in the pregnant mouse: an obstetric-fetal pharmacology research unit network and university of Washington specialized center of research study[J]. Mol Pharmacol, 2008, 73(3):949-959.
13
Imai Y, Nakane M, Kage K, et al. C421A polymorphism in the human breast cancer resistance protein gene is associated with low expression of Q141K protein and low-level drug resistance[J]. Mol Cancer Ther, 2002, 1(8):611-616.
14
Zamber CP, Lamba JK, Yasuda K, et al. Natural allelic variants of breast cancer resistance protein (BCRP) and their relationship to BCRP expression in human intestine[J]. Pharmacogenetics, 2003, 13(1):19-28.
15
De Jong FA, Marsh S, Mathijssen RH, et al. ABCG2 pharmacogenetics: ethnic differences in allele frequency and assessment of influence on irinotecan disposition[J]. Clin Cancer Res, 2004, 10(17):5889-5894.
16
Backstrom G, Taipalensuu J, Melhus H, et al. Genetic variation in the ATP-binding cassette transporter gene ABCG2 (BCRP) in a Swedish population[J]. Eur J Pharm Sci, 2003, 18(5):359-364.
17
Hutson JR, Koren G, Matthews SG. Placental P-glycoprotein and breast cancer resistance protein: influence of polymorphisms on fetal drug exposure and physiology[J]. Placenta, 2010, 31(5):351-357.
18
Ieiri I. Functional significance of genetic polymorphisms in P-glycoprotein (MDR1, ABCB1) and breast cancer resistance protein (BCRP, ABCG2)[J]. Drug Metab Pharmacokinet, 2012, 27(1):85-105.
19
Kobayashi D, Ieiri I, Hirota T, et al. Functional assessment of ABCG2 (BCRP) gene polymorphisms to protein expression in human placenta[J]. Drug Metab Dispos, 2005, 33(1):94-101.
20
Andrade SE, Raebel MA, Morse AN, et al. Use of prescription medications with a potential for fetal harm among pregnant women[J]. Pharmacoepidemiol Drug Saf, 2006, 15(8):546-554.
21
Ifergan I, Jansen G, Assaraf YG. Cytoplasmic confinement of breast cancer resistance protein (BCRP/ABCG2) as a novel mechanism of adaptation to short-term folate deprivation[J]. Mol Pharmacol, 2005, 67(4):1349-1359.
22
Ifergan I, Shafran A, Jansen G, et al. Folate deprivation results in the loss of breast cancer resistance protein (BCRP/ABCG2) expression:a role for BCRP in cellular folate homeostasis[J]. J Biol Chem, 2004, 279(24):25527-25534.
23
Bedard T, Lowry RB, Sibbald B, et al. Folic acid fortification and the birth prevalence of congenital heart defect cases in Alberta, Canada[J]. Birth Defects Res A Clin Mol Teratol, 2013, 97(8):564-570.
24
Li X, Li S, Mu D, et al. The association between periconceptional folic acid supplementation and congenital heart defects: a case-control study in China[J]. Prev Med, 2013, 56(6):385-389.
25
Grosse SD, Collins JS. Folic acid supplementation and neural tube defect recurrence prevention[J].Birth Defects Res A Clin Mol Teratol, 2007, 79(11):737-742.
26
Wilson RD, Johnson JA, Wyatt P, et al. Pre-conceptional vitamin/folic acid supplementation 2007: the use of folic acid in combination with a multivitamin supplement for the prevention of neural tube defects and other congenital anomalies[J]. J Obstet Gynaecol Can, 2007, 29(12):1003-1026.
27
Wolff T, Witkop CT, Miller T, et al. Folic acid supplementation for the prevention of neural tube defects: an update of the evidence for the U.S. Preventive Services Task Force[J]. Ann Intern Med, 2009, 150(9):632-639.
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