6 ABCB1 603 sol ratio in the TT genotype group was significantly higher than those in the CT and CC + CT genotype groups P < Multivariable regr

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1 32 6 Vol. 32 No Journal of Jinan University Medicine Edition Dec ABCB1 1 1 Berthold Hocher Institute of Nutritional Science University of Potsdam D Nuthetal-Potsdam Germany ABCB1 PCR-RFLP ABCB1 C3435T ABCB1 /C3435T CC CT TT % % % % % % P > TT CT CC + CT P < TT CT CC + CT P < ABCB1 /C3435T R 2 = B = P = R 2 = B = P = ABCB1 /C3435T ABCB1 / C3435T ABCB1 /C3435T P- R A Relationship between ABCB1 polymorphism and the cortisol transportation in maternofetal interface LI Jian 1 WANG Zi-neng 1 HOCHER Berthold 2 CHEN You-peng 3 1. Department of Obstetrics and Gynecology the First Affiliated Hospital Jinan University Guangzhou China 2. Institute of Nutritional Science University of Potsdam D Nuthetal-Potsdam Germany 3. Department of Infectious Diseases the First Affiliated Hospital Jinan University Guangzhou China Abstract Aim To explore the relationship between ABCB1 polymorphisms and the cortisol transportation in maternofetal interface during normal pregnancy. Methods the ABCB1 /C3435T genotype was examined in 262 fetal and 142 maternal blood samples during normal pregnancy by PCR-RFLP. Blood serum cortisol levels were measured by fluorescence polarization immunoassay. Results The frequency of the gene polymorphisms of ABCB1 /C3435T In the fetal group the frequency of CC CT TT genotype were % % %. Respectively and in the maternal group the frequency of CC CT TT genotype were % % % respectively. There was no statistic difference between the two groups P > The fetal blood serum cortisol in the TT genotype group was significantly lower than those in the CT and CC + CT genotype groups P < The blood serum maternal /fetal corti B Hcher Tel twangzineng@ jnu. edu. cn

2 6 ABCB1 603 sol ratio in the TT genotype group was significantly higher than those in the CT and CC + CT genotype groups P < Multivariable regression analyses showed that the fetal ABCB1 /C3435T genotype revealed a significantly negative correlation with fetal blood serum cortisol R 2 = B = P = and a positive correlation with blood serum maternal /fetal cortisol ratio R 2 = B = P = The maternal ABCB1 / C3435T polymorphism assessed by comparable models showed no significant association with the blood serum cortisol level. Conclusion The fetal ABCB1 /C3435T polymorphisms is related to the cortisol transportation in maternofetal interface during normal pregnancy. Key words ABCB1 /C3435T p-glycoprotein maternofetal interface cortisol 5 ~ β 11β-HSD P- ABC 5 1 ~ 4 MDR1 ABCB1 3 DNA 2-4 Mark 5 P- Sau3AI Taq 11β-HSD2 DNA Takara P- 6 ABCB P- 1 ABCB1 /C3435T ABCB1 DNA DNA PCR 26 C3435T Sau3AI 262 PCR Sau3AI 172 bp 76 bp PCR 3% HIV bp 2 CC 248 bp 1 TT bp 3 CT 10% PCR 262 PCR-RFLP PCR AxSYM 2 Abbott 2G /05 ml EDTA DNA - 20 PCR 5 '-TGCTGGTC- CTGAAGTTGATCTGTGAAC -3' 5'- ACATTAG- GCAGTGACTCGATGAAGGCA -3' 1 μl DNA PCR 248 bp PCR Sau3AI 2 SPSS 13. 0

3 ± x 珋 ± s 2 x 珔 ± s Hard-Wein- n berg CC CT C ABCB1 /C3435T TT C CC ± ± ± ~ 2 P < c ± ± ± CT TT CC + CT 5 94 ANOVA t ± ± ~ 3 P < ABCB1 /C3435T P < ABCB1 /C3435T 2 Fisher C3435T 2. 1 Hardy-Weinberg P > P > ABCB1 /C3435T x 珔 ± t ABCB1 /C3435T TT s CC CT CC + CT n c P < TT n 3 CC CT CC + CT P < ABCB1 /C3435T C C T T CC CC CT CT TT TT / / / / / / / /% /% % % /% ABCB1 /C3435T x 珔 ± s n c c / CC ± ± ± CT ± ± ± CC + CT ± ± ± TT ± ± ± TT 1 P < ABCB1 /C3435T ABCB1 /C3435T R 2 = B = P = ABCB1 /C3435T ABCB1 /C3435T CC + CT TT ABCB1 /C3435T ABCB1 /C3435T R 2 = B = P = ABCB1 /C3435T ABCB1 /C3435T R 2 = B = P = 5

4 6 ABCB ABCB1 /C3435T x 珔 ± s n c c CC ± ± ± CT ± ± ± CC + CT ± ± ± TT ± ± ± / P- G2677T /A TT CC /GG P- T P- P- P- P- Hemauer 21 AB- 12 Pariante 13 CB1 P- P- C3435T G2677T /A T P- Saitoh 14 C3435T C1236T T P- Mark P- C3435T C1236T 5 BeWo P- P- BeWoMDR P P- 23 ABCB1 T P- 11β-HSD2 P- P- AB- CB1 100 ABCB1 P- 15 ABCB1 C3435T G2677T /A C1236T BENEDIKTSSON R CALDER A A EDWARDS C R et C3435T ABCB1 al. Placental 11 beta-hydroxysteroid dehydrogenase a ABCB1 /C3435T key regulator of fetal glucocorticoid exposure J. Clin Hardy-Weinberg C3435T Endocrinol Oxf MIZUTANI T MASUDA M NAKAI E et al. Genuine functions of P-glycoprotein ABCB1 J. Curr Drug Metab UEDA K OKAMURA N HIRAI M et al. Human P- 19 glycoprotein transports cortisol aldosterone and dexamethasone but not progesterone J. J Biol Chem YATES C R CHANG C KEARBEY J D et al. Structural determinants of P-glycoprotein-mediated transport of ABCB1 TT MARK P J WADDELL B J. P-glycoprotein restricts access of cortisol and dexamethasone to the glucocorticoid ABCB1 /C3435T T receptor in placental BeWo cells J. Endocrinology Hitzl 20 ABCB1 / C3435T TT /tt P- CC /cc C3435T glucocorticoids J. Pharm Res

5 GIL S SAURA R FORESTIER F et al. P-glycoprotein expression of the human placenta during pregnancy J. Placenta / M NAKAMURA Y IKEDA S FURUKAWA T et al. Function of P-glycoprotein expressed in placenta and mole J. Biochem Biophys Res Commun SUN M KINGDOM J BACZYK D et al. Expression of the multidrug resistance P-glycoprotein ABCB1 glycoprotein in the human placenta decreases with advancing gestation J. Placenta / NOVOTNA M LIBRA A KOPECKY M et al. P-glycoprotein expression and distribution in the rat placenta during pregnancy J. Reprod Toxicol KALABIS G M PETROPOULOS S GIBB W et al. Multidrug resistance phosphoglycoprotein ABCB1 expression in the guinea pig placenta developmental changes and regulation by betamethasone J. Can J Physiol Pharmacol LANKAS G R WISE L D CARTWRIGHT M E et al. Placental P-glycoprotein deficiency enhances susceptibility to chemically induced birth defects in mice J. Reprod Toxicol PARIANTE C M MAKOFF A LOVESTONE S et al. Antidepressants enhance glucocorticoid receptor function in vitro by modulating the membrane steroid transporters J. Br J Pharmacol NAKAYAMA A EGUCHI O HATAKEYAMA M et al. Different absorption behaviors among steroid hormones due to possible interaction with P-glycoprotein in the rat small intestine J. Biol Pharm Bull XU PING JIANG ZHIPING ZHANG BIKUI et al. Impact of MDR1 haplotypes derived from C1236T G2677T /A and C3435T on the pharmacokinetics of single-dose oral digoxin in healthy Chinese volunteers J. Pharmacology WEITZMAN E D FUKUSHIMA D NOGEIRE C et al. Twenty-four hour pattern of the episodic secretion of cortisol in normal subjects J. J Clin Endocrinol Metab KIVLIGHAN K T DIPIETRO J A COSTIGAN K A et al. Diurnal rhythm of cortisol during late pregnancy associations with maternal psychological well-being and fetal growth J. Psychoneuroendocrinology GOLAND R S TROPPER P J WARREN W B et al. Concentrations of corticotrophin-releasing hormone in the umbilical-cord blood of pregnancies complicated by preeclampsia J. Reprod Fertil Dev LAO T T PANESAR N S. The effect of labour on prolactin and cortisol concentrations in the mother and the fetus J. Eur J Obstet Gynecol Reprod Biol HITZL M SCHAEFFELER E HOCHER B et al. Variable expression of P-glycoprotein in the human placenta and its association with mutations of the multidrug resistance 1 gene MDR1 ABCB1 J. Pharmacogenetics HEMAUER S J NANOVSKAYA T N ABDEL-RAH- MAN S Z et al. Modulation of human placental P-glycoprotein expression and activity by MDR1 gene polymorphisms J. Biochem Pharmacol GREEN H SODERKVIST P ROSENBERG P et al. Pharmacogenetic studies of Paclitaxel in the treatment of ovarian cancer J. Basic Clin Pharmacol Toxicol TAUBERT D VON BECKERATH N GRIMBERG G et al. Impact of P-glycoprotein on clopidogrel absorption J. Clin Pharmacol Ther

综合报道

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