Schneider Michael O, Pretscher Jutta, Goecke Tamme W, Häberle Lothar, Engel Anne, Kornhuber Johannes, Eichler Anna, Ekici Arif B, Beckmann Matthias W, Fasching Peter A, Schwenke Eva
Erlangen University Perinatal Center, Department of Gynecology and Obstetrics, Erlangen University Hospital, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsstrasse 21-23, 91054, Erlangen, Germany.
Department of Obstetrics, RoMed Clinic Rosenheim, Rosenheim, Germany.
Arch Gynecol Obstet. 2023 Jun;307(6):1763-1770. doi: 10.1007/s00404-022-06644-8. Epub 2022 Jun 10.
The aim of this study was to conduct an association analysis of depressive symptoms and polymorphisms in the ESR1, PGR, CYP19A1, and COMT genes in pregnant and postpartum women.
The Franconian Maternal Health Evaluation Study (FRAMES) recruited healthy pregnant women prospectively for assessment of maternal and fetal health. The German version of the 10-item Edinburgh Postnatal Depression Scale (EPDS) was completed at three time points in this prospective cohort study. Visit 1 was at study entry in the third trimester of pregnancy, visit 2 was shortly after birth, and visit 3 was 6-8 months after birth. Germline DNA and depression measurements from 361 pregnant women were available for analysis. Six single nucleotide polymorphisms (SNPs) in the above-mentioned genes were genotyped. After reconstruction of haplotypes for PGR (rs1042838 and rs10895068) and CYP19A1 (rs10046 and rs4646), a multifactorial linear mixed model was applied to the data to describe the association between haplotypes and depression values. The single SNPs for ESR1 (rs488133) and COMT (rs4680) were analyzed separately using linear mixed models analogously.
The mean antepartum EPDS measurement was 5.1, the mean postpartal measurement after 48-72 h was 3.5, and the mean value 6-8 months postpartum was 4.2. The SNPs in PGR were reconstructed into three haplotypes. The most common haplotype was GG, with 63.43% of patients carrying two copies and 33.52% carrying one copy. For haplotype GA, the group of carriers of two copies (0.28%) was combined with the carriers of one copy (9.70%). Haplotype reconstruction using CYP19A1 SNPs resulted in three haplotypes. The most common haplotype was TC, with 25.48% of patients carrying two copies and 51.52% one copy. None of the haplotype blocks and neither of the two single SNPs showed any significant associations with EPDS values.
The candidate haplotypes analyzed in PGR and CYP19A1 and single SNPs in ESR1 and COMT did not show any association with depression scores as assessed by EPDS in this cohort of healthy unselected pregnant women.
本研究旨在对孕妇和产后妇女的抑郁症状与雌激素受体1(ESR1)、孕激素受体(PGR)、细胞色素P450 19A1(CYP19A1)和儿茶酚-O-甲基转移酶(COMT)基因多态性进行关联分析。
弗兰肯地区孕产妇健康评估研究(FRAMES)前瞻性招募健康孕妇以评估母婴健康。在这项前瞻性队列研究中,在三个时间点完成了德文版的10项爱丁堡产后抑郁量表(EPDS)。访视1在妊娠晚期研究入组时,访视2在出生后不久,访视3在出生后6 - 8个月。可获得361名孕妇的生殖系DNA和抑郁测量数据用于分析。对上述基因中的6个单核苷酸多态性(SNP)进行基因分型。在对PGR(rs1042838和rs10895068)和CYP19A1(rs10046和rs4646)进行单倍型重建后,对数据应用多因素线性混合模型来描述单倍型与抑郁值之间的关联。对ESR1(rs488133)和COMT(rs4680)的单个SNP分别使用类似的线性混合模型进行分析。
产前EPDS测量的平均值为5.1,产后48 - 72小时的平均值为3.5,产后6 - 8个月的平均值为4.2。PGR中的SNP被重建为三种单倍型。最常见的单倍型是GG,63.43%的患者携带两个拷贝,33.52%的患者携带一个拷贝。对于单倍型GA,两个拷贝的携带者组(0.28%)与一个拷贝的携带者(9.70%)合并。使用CYP19A1 SNP进行单倍型重建产生了三种单倍型。最常见的单倍型是TC,25.48% 的患者携带两个拷贝,51.52% 的患者携带一个拷贝。没有任何单倍型块以及两个单个SNP与EPDS值显示出任何显著关联。
在该组未经过选择的健康孕妇中,PGR和CYP19A1中分析的候选单倍型以及ESR1和COMT中的单个SNP与EPDS评估的抑郁评分均未显示出任何关联。