Association of MAOA, 5-HTT, and NET promoter polymorphisms with gene expression and protein activity in human placentas.
Association of MAOA, 5-HTT, and NET promoter polymorphisms with gene expression and protein activity in human placentas.
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MAOA、5-HTT 和 NET 启动子多态性与人胎盘基因表达和蛋白质活性的关联。
DOI：
10.1152/physiolgenomics.00220.2009
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发表时间：
2010
影响因子：
4.6
通讯作者：
Holden,JeanetteJA
中科院分区：
文献类型：
--
作者：
Zhang,Huiping;Smith,GraemeN;Liu,Xudong;Holden,JeanetteJA
单胺氧化酶A（MAOA）、5-羟色胺转运体（5-HTT）和去甲肾上腺素转运体（NET）可能在调节母体单胺神经递质经胎盘转运至胎儿中起重要作用。我们研究了MAOA（uVNTR）、5-HTT（5-HTTLPR）和NET（NETpPR AAGG4）启动子多态性是否会影响人类胎盘中的基因表达和蛋白活性。收集正常足月人胎盘（n = 73），并测定胎盘MAOA、5-HTT和NET mRNA水平和蛋白活性。比较不同基因型组间的mRNA水平或蛋白活性。MAOAuVNTR 4-重复等位基因的半合子（男性胎儿）或纯合子（女性胎儿）胎盘的MAOA mRNA水平显著高于3-重复等位基因的半合子或纯合子（P = 0.001）。但两组基因型的MAOA酶活性差异无统计学意义（P = 0.161）。携带5-HTTLPR短（S）等位基因（S/S + S/L）的胎盘5-HTTmRNA水平和5-羟色胺摄取率显著低于携带5-HTTLPR长（L）等位基因（L/L）的胎盘（mRNA：P <0.001; 5-羟色胺转运活性：P <0.001）。NETAAGG4L4等位基因纯合子的胎盘NET mRNA水平以及多巴胺和去甲肾上腺素摄取率显著高于S4/L4基因型的胎盘（mRNA：P <0.001;多巴胺转运活性：P = 0.012;去甲肾上腺素转运活性：P = 0.011）。这些发现表明MAOA、5-HTT和NET三种启动子多态性影响人类胎盘中这些基因的基因表达水平和蛋白活性，可能导致母体单胺神经递质的胎儿水平不同，这可能对胎儿神经发育产生影响。
Monoamine oxidase A (MAOA) and the transporters for serotonin (5-HTT) and norepinephrine (NET) may play important roles in regulating maternal monoamine neurotransmitters transferred across the placenta to the fetus. We investigated whether promoter polymorphisms inMAOA(uVNTR),5-HTT(5-HTTLPR), andNET(NETpPR AAGG4) could influence gene expression and protein activity in human placentas. Normal term human placentas (n= 73) were collected, and placental MAOA, 5-HTT, and NET mRNA levels and protein activity were determined. The mRNA levels or protein activities were compared between different genotype groups. Placentas hemizygous (male fetus) or homozygous (female fetus) forMAOAuVNTR 4-repeat allele had significantly higher MAOA mRNA levels than those hemizygous or homozygous for the 3-repeat allele (P= 0.001). However, no significant difference in MAOA enzyme activity was found for these two groups of genotypes (P= 0.161). Placentas with the5-HTTLPRshort (S)-allele (S/S+S/L) had significantly lower 5-HTT mRNA levels and serotonin uptake rate than those homozygous for the long (L)-allele (L/L) (mRNA:P< 0.001; serotonin transporting activity:P< 0.001). Placentas homozygous for theNETAAGG4L4allele had significantly higher NET mRNA levels, as well as dopamine and norepinephrine uptake rates, than those with the S4/L4genotype (mRNA:P< 0.001; dopamine transporting activity:P= 0.012; norepinephrine transporting activity:P= 0.011). These findings suggest that the three promoter polymorphisms ofMAOA,5-HTT, andNETinfluence gene expression levels and protein activity of these genes in human placentas, potentially leading to different fetal levels of maternal monoamine neurotransmitters, which may have an impact on fetal neurodevelopment.