TY  - JOUR
A1  - Yang, Fang
A1  - Lai, Xinlong
A1  - Deng, Li
A1  - Liu, Xiaoxiao
A1  - Li, Jian
A1  - Zeng, Shuixiu
A1  - Zhang, Cheng
A1  - Hocher, Carl-Friedrich
A1  - Hocher, Berthold
T1  - Association of endothelin-1 gene polymorphisms with the clinical phenotype in primary nephrotic syndrome of children
JF  - Life sciences : molecular, cellular and functional basis of therapy
N2  - Aims:This study aims to investigate the relationship between plasma endothelin-1 (ET-1) concentrations, ET-1 gene polymorphisms in loci rs5370, rs1630736, 3A/4A and clinical features of primary nephrotic syndrome (NS) in children.
 Materials and methods: Thirty-six children with primary NS were selected as case group, and 94 healthy children were selected as control group. All subjects were genotyped for three single nucleotide polymorphisms (SNPs) (rs5370, rs10478694 [3A4A) and rs 1630736) in the ET-1 gene by gene sequencing. The plasma ET-1 concentrations were measured using a radio-immunoassay.
 Key findings: Plasma ET-1 concentrations were higher in NS patients (P = 0.007) as compared to healthy children. The allele frequencies between control and NS patients were significantly different only with respect to the rs10478694 SNP of the ET-1 gene. The allele frequencies between control and NS patients for the rs5370 SNP showed a trend towards difference (P = 0.057). Plasma cholesterol in NS patients is associated with both: the Cl genotype in locus rs5370 and the 3A4A genotype in locus rs10478694 (P < 0.05 in both cases).
 Significance: The ET systems might play a disease modifying role in pediatric NS. Plasma cholesterol, a hallmark of NS. seems to be associated with genetic variations within the human ET-1 gene. (C) 2014 Elsevier Inc. All rights reserved.
KW  - Endothelin-1
KW  - Gene polymorphism
KW  - Childhood nephrotic syndrome
KW  - Cholesterol
Y1  - 2014
U6  - https://doi.org/10.1016/j.lfs.2014.04.010
SN  - 0024-3205
SN  - 1879-0631
VL  - 118
IS  - 2
SP  - 446
EP  - 450
PB  - Elsevier
CY  - Oxford
ER  - 
TY  - JOUR
A1  - Reichetzeder, Christoph
A1  - Chen, Hong
A1  - Foeller, Michael
A1  - Slowinski, Torsten
A1  - Li, Jian
A1  - Chen, You-Peng
A1  - Lang, Florian
A1  - Hocher, Berthold
T1  - Maternal vitamin D deficiency and fetal programming - lessons learned from humans and mice
JF  - Kidney & blood pressure research : official organ of the Gesellschaft für Nephrologie
N2  - Background/Aims: Cardiovascular disease partially originates from poor environmental and nutritional conditions in early life. Lack of micronutrients like 25 hydroxy vitamin D-3 (25OHD) during pregnancy may be an important treatable causal factor. The present study explored the effect of maternal 25OHD deficiency on the offspring. Methods: We performed a prospective observational study analyzing the association of maternal 25OHD deficiency during pregnancy with birth outcomes considering confounding. To show that vitamin D deficiency may be causally involved in the observed associations, mice were set on either 25OHD sufficient or insufficient diets before and during pregnancy. Growth, glucose tolerance and mortality was analyzed in the F1 generation. Results: The clinical study showed that severe 25OHD deficiency was associated with low birth weight and low gestational age. ANCOVA models indicated that established confounding factors such as offspring sex, smoking during pregnancy and maternal BMI did not influence the impact of 25OHD on birth weight. However, there was a significant interaction between 25OHD and gestational age. Maternal 25OHD deficiency was also independently associated with low APGAR scores 5 minutes postpartum. The offspring of 25OHD deficient mice grew slower after birth, had an impaired glucose tolerance shortly after birth and an increased mortality during follow-up. Conclusions: Our study demonstrates an association between maternal 25OHD and offspring birth weight. The effect of 25OHD on birth weight seems to be mediated by vitamin D controlling gestational age. Results from an animal experiment suggest that gestational 25OHD insufficiency is causally linked to adverse pregnancy outcomes. Since birth weight and prematurity are associated with an adverse cardiovascular outcome in later life, this study emphasizes the need for novel monitoring and treatment guidelines of vitamin D deficiency during pregnancy.
KW  - Vitamin D
KW  - Birth weight
KW  - Preterm delivery
KW  - Fetal programming
KW  - Glucose tolerance
KW  - Cardiovascular diseases
Y1  - 2014
U6  - https://doi.org/10.1159/000355809
SN  - 1420-4096
SN  - 1423-0143
VL  - 39
IS  - 4
SP  - 315
EP  - 329
PB  - Karger
CY  - Basel
ER  - 
TY  - JOUR
A1  - Lu, Yong-Ping
A1  - Lung, Xu-Jing
A1  - Xiao, Xiao-Min
A1  - Huang, Si-Min
A1  - Liu, Zhi-Wei
A1  - Li, Jian
A1  - Hocher, Berthold
A1  - Chen, You-Peng
T1  - Telbivudine during the second and third trimester of pregnancy interrupts HBV intrauterine transmission: a systematic review and meta-analysis
JF  - Clinical laboratory : the peer reviewed journal for clinical laboratories and laboratories related to blood transfusion
N2  - Beckground: Evaluate the efficacy and safety of telbivudine during the 2nd and 3rd trimester of pregnancy in intrauterine transmission of hepatitis B virus (HBV). Based on the principle of Cochrane systematic reviews, a database was constructed from Medline, EMBASE, Cochrane Library, the US National Science Digital Library (NSDL), the China Biological Medicine Database (CBM-disc), and contact with Chinese experts in the field from November 2006 to February 2013.
 Results: Either the Mantel-Haenszel or Inverse Variance fixed-effects model or Mantel-Haenszel or Inverse Variance random-effects model was applied for all analyses indicated by odds ratio (OR) and 95% confidence interval (CI). The meta-analysis based on new onset of HBsAg seropositivity of infants at 6 - 12 months postpartum revealed that the control group had an intrauterine transmission rate of 8.25 - 42.31%. This rate was reduced to 0 - 14.29% in the telbivudine treatment group (OR 0.09, 95% CI 0.04 - 0.22, including seven trials, p < 0.001). The rates of intrauterine transmission based on new onset of HBV DNA seropositivity of infants at 6 - 12 months postpartum were 8.25 - 19.23% in the control group and 0 - 3.57% in the treatment group (OR 0.07, 95% CI 0.02 - 0.22, p < 0.001, including only five trials, since two trials had no data on HBV DNA in infants). With the exception of CK elevations, adverse effect frequencies were similar in both groups.
 Conclusions: Telbivudine is an effective and safe drug for preventing intrauterine transmission of HBV.
KW  - telbivudine
KW  - meta-analysis
KW  - intrauterine
KW  - transmission of hepatitis B virus (HBV)
KW  - clinical studies
KW  - safety efficacy
Y1  - 2014
U6  - https://doi.org/10.7754/Clin.Lab.2013.130408
SN  - 1433-6510
VL  - 60
IS  - 4
SP  - 571
EP  - 586
PB  - Clin Lab Publ., Verl. Klinisches Labor
CY  - Heidelberg
ER  - 
TY  - JOUR
A1  - Li, Jian
A1  - Wang, Zi-Neng
A1  - Schlemm, Ludwig
A1  - Pfab, Thiemo
A1  - Xiao, Xiao-Min
A1  - Chen, You-Peng
A1  - Hocher, Berthold
T1  - Low birth weight and elevated head-to-abdominal circumference ratio are associated with elevated fetal glycated serum protein concentrations
JF  - Journal of hypertension
N2  - Objective To analyze the association between low birth weight, head-to-abdominal circumference ratio, and insulin resistance in early life.
 Method and results Glycated serum proteins (GSPs) were quantified at delivery in 612 Chinese mother/child pairs serving as a surrogate of maternal and fetal glycemia. Differential ultrasound examination of the fetal's body (head circumference, biparietal diameter, pectoral diameter, abdominal circumference, and femur length) was done in average 1 week prior to delivery. Multivariable regression analysis considering gestational age at delivery, the child's sex, maternal BMI, maternal age at delivery, maternal body weight, and pregnancyinduced hypertension revealed that fetal GSP was inversely associated with birth weight (R(2) = 0.416; P < 0.001). Fetal GSP was furthermore positively associated with the head-to-abdominal circumference ratio, whereas the maternal GSP was negatively correlated with the offspring's head-to-abdominal circumference ratio (R(2) = 0.285; P = 0.010 and R(2) = 0.261; P = 0.020, respectively). The increased head-to-abdominal circumference ratio in newborns with higher fetal GSP is mainly due to a reduced abdominal circumference rather than reduced growth of the brain.
 Conclusion The disproportional intrauterine growth is in line with the concept of so-called brain sparing, a mechanism maintaining the intrauterine growth of the brain at the expense of trunk growth. Our data suggest that the low birth weight phenotype, linked to cardiovascular diseases like hypertension in later life, might be a phenotype of disproportional intrauterine growth retardation and early life insulin resistance.
KW  - disproportional intrauterine growth retardation
KW  - insulin resistance
KW  - low birth weight
KW  - ultrasound
Y1  - 2011
U6  - https://doi.org/10.1097/HJH.0b013e328349a2e6
SN  - 0263-6352
VL  - 29
IS  - 9
SP  - 1712
EP  - 1718
PB  - Lippincott Williams & Wilkins
CY  - Philadelphia
ER  - 
TY  - JOUR
A1  - Li, Jian
A1  - Wang, Zi-Neng
A1  - Chen, You-Peng
A1  - Dong, Yun-Peng
A1  - Shuai, Han-Lin
A1  - Xiao, Xiao-Min
A1  - Reichetzeder, Christoph
A1  - Hocher, Berthold
T1  - Late gestational maternal serum cortisol is inversely associated with fetal brain growth
JF  - Neuroscience & biobehavioral reviews : official journal of the International Behavioral Neuroscience Society
N2  - To analyze the association between fetal brain growth and late gestational blood serum cortisol in normal pregnancy.Blood total cortisol was quantified at delivery in 432 Chinese mother/child pairs. Key inclusion criteria of the cohort were: no structural anomalies of the newborn, singleton pregnancy, no alcohol abuse, no drug abuse or history of smoking no hypertensive disorders and no impairment of glucose tolerance and no use of steroid medication during pregnancy. Differential ultrasound examination of the fetal body was done in early (gestational day 89.95 +/- 7.31), middle (gestational day 160.17 16.12) and late pregnancy (gestational day 268.89 +/- 12.42). Newborn's cortisol was not correlated with any of the ultrasound measurements during pregnancy nor with birth weight. Multivariable regression analysis, considering timing of the ultrasound examination, the child's sex, maternal BMI, maternal age, maternal body weight at delivery, the timing of cortisol measurement and maternal uterine contraction states, revealed that maternal serum total cortisol was significantly negative correlated with ultrasound parameters describing the fetal brain: late biparietal diameter (R-2 =0.512, p =0.009), late head circumference (R-2 = 0.498, p= 0.001), middle biparietal diameter (R-2= 0.819, p = 0.013), middle cerebellum transverse diameter R-2 = 0.76, p= 0.014) and early biparietal diameter(R-2 = 0.819, p = 0.013). The same analysis revealed that birth weight as well as ultrasound parameters such as abdominal circumference and femur length were not correlated to maternal cortisol levels.
 In conclusion, our study demonstrates that maternal cortisol secretion within physiological ranges may be inversely correlated to fetal brain growth but not to birth weight. It remains to be demonstrated whether maternal cortisol secretion negatively influencing fetal brain growth translates to adverse neurological outcomes in later life.
KW  - Brain development
KW  - Fetal programming
KW  - Cortisol Maternal cortisol
KW  - Head circumference
KW  - Biparietal diameter
Y1  - 2012
U6  - https://doi.org/10.1016/j.neubiorev.2011.12.006
SN  - 0149-7634
VL  - 36
IS  - 3
SP  - 1085
EP  - 1092
PB  - Elsevier
CY  - Oxford
ER  - 
TY  - JOUR
A1  - Li, Jian
A1  - Wang, Zi-Neng
A1  - Chen, You-Peng
A1  - Dong, Yun-Peng
A1  - Mao, Xiao-Min
A1  - Hocher, Berthold
T1  - Association of fetal but not maternal P-glycoprotein C3435T polymorphism with fetal growth and birth weight, a possible risk factor for cardiovascular diseases in later life
JF  - Clinical laboratory : the peer reviewed journal for clinical laboratories and laboratories related to blood transfusion
N2  - Background: The multidrug transporter P-glycoprotein (PGP) is expressed in the human placenta. In particular the C3435T ABCB1 polymorphism was associated with altered tissue expression of PGP in the human placenta. However, the potential functional impact of this polymorphism on the offspring is unknown so far.
 Methods: We analyzed the impact of the ABCB1/C3435T polymorphism on fetal growth in 262 mother/child pairs. Fetal growth was assessed by differential ultrasound examination of the fetal body prior to birth and by measuring birth weight.
 Results: The maternal ABCB1/C3435T polymorphism showed no trend for an association with birth weight or any ultrasound parameter describing late gestational fetal body shape. Genotyping the newborns, however, demonstrated that newborns carrying two copies of the T allele had a birth weight of 3176.39 g, whereas CT and CC newborns had a birth weight of 3345.04 g (p = 0.022). Adjusting for gestational age at delivery, child's gender, maternal BM1, maternal age and body weight at delivery confirmed this finding (p = 0.009). Considering gestational day of late ultrasound examination, gestational age at delivery, child's gender, maternal BMI, maternal age and maternal body weight at delivery, the fetal ABCB1/C3435T genotype revealed likewise a significant negative correlation with abdominal diameter and abdominal circumference (R-2 = 0.538, p = 0.010 and R-2 = 0.534, p = 0.005, respectively).
 Conclusions: Low birth weight may be a risk factor for cardiovascular diseases in later life. The fetal ABCB1/C3435T gene polymorphism may contribute to this risk. Since PGP controls transport of various biological agents, we suggest that PGP is involved in the transport of biological agents to the fetus that are important for normal fetal growth.
Y1  - 2012
U6  - https://doi.org/10.7754/Clin.Lab.2012.110920
SN  - 1433-6510
VL  - 58
IS  - 9-10
SP  - 1085
EP  - 1089
PB  - Clin Lab Publ., Verl. Klinisches Labor
CY  - Heidelberg
ER  - 
TY  - JOUR
A1  - Li, Jian
A1  - Shen, Jinhua
A1  - Zhang, Xiaoli
A1  - Peng, Yangqin
A1  - Zhang, Qin
A1  - Hu, Liang
A1  - Reichetzeder, Christoph
A1  - Zeng, Suimin
A1  - Li, Jing
A1  - Tian, Mei
A1  - Gong, Fei
A1  - Lin, Ge
A1  - Hocher, Berthold
T1  - Risk factors associated with preterm birth after IVF/ICSI
JF  - Scientific reports
N2  - In vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) is associated with an increased risk of preterm (33rd-37th gestational week) and early preterm birth (20th-32nd gestational week). The underlying general and procedure related risk factors are not well understood so far. 4328 infertile women undergoing IVF/ICSI were entered into this study. The study population was divided into three groups: (a) early preterm birth group (n = 66), (b) preterm birth group (n = 675) and (c) full-term birth group (n = 3653). Odds for preterm birth were calculated by stepwise multivariate logistic regression analysis. We identified seven independent risk factors for preterm birth and four independent risk factors for early preterm birth. Older (> 39) or younger (< 25) maternal age (OR: 1.504, 95% CI 1.108-2.042, P = 0.009; OR: 2.125, 95% CI 1.049-4.304, P = 0.036, respectively), multiple pregnancy (OR: 9.780, 95% CI 8.014-11.935, P < 0.001; OR: 8.588, 95% CI 4.866-15.157, P < 0.001, respectively), placenta previa (OR: 14.954, 95% CI 8.053-27.767, P < 0.001; OR: 16.479, 95% CI 4.381-61.976, P < 0.001, respectively), and embryo reduction (OR: 3.547, 95% CI 1.736-7.249, P = 0.001; OR: 7.145, 95% CI 1.990-25.663, P = 0.003, respectively) were associated with preterm birth and early preterm birth, whereas gestational hypertension (OR: 2.494, 95% CI 1.770-3.514, P < 0.001), elevated triglycerides (OR: 1.120, 95% CI 1.011-1.240, P = 0.030) and shorter activated partial thromboplastin time (OR: 0.967, 95% CI 0.949-0.985, P < 0.001) were associated only with preterm birth. In conclusion, preterm and early preterm birth risk factors in patients undergoing assisted IVF/ICSI are in general similar to those in natural pregnancy. The lack of some associations in the early preterm group was most likely due to the lower number of early preterm birth cases. Only embryo reduction represents an IVF/ICSI specific risk factor.
Y1  - 2022
U6  - https://doi.org/10.1038/s41598-022-12149-w
SN  - 2045-2322
VL  - 12
IS  - 1
PB  - Nature Research
CY  - Berlin
ER  - 
TY  - JOUR
A1  - Li, Jian
A1  - Lu, Yong-Ping
A1  - Tsuprykov, Oleg
A1  - Hasan, Ahmed Abdallah Abdalrahman Mohamed
A1  - Reichetzeder, Christoph
A1  - Tian, Mei
A1  - Zhang, Xiao Li
A1  - Zhang, Qin
A1  - Sun, Guo-Ying
A1  - Guo, Jingli
A1  - Gaballa, Mohamed Mahmoud Salem Ahmed
A1  - Peng, Xiao-Ning
A1  - Lin, Ge
A1  - Hocher, Berthold
T1  - Folate treatment of pregnant rat dams abolishes metabolic effects in female offspring induced by a paternal pre-conception unhealthy diet
JF  - Diabetologia : journal of the European Association for the Study of Diabetes (EASD)
N2  - Aims/hypothesis Paternal high-fat diet prior to mating programmes impaired glucose tolerance in female offspring. We examined whether the metabolic consequences in offspring could be abolished by folate treatment of either the male rats before mating or the corresponding female rats during pregnancy. Methods Male F0 rats were fed either control diet or high-fat, high-sucrose and high-salt diet (HFSSD), with or without folate, before mating. Male rats were mated with control-diet-fed dams. After mating, the F0 dams were fed control diet with or without folate during pregnancy.
KW  - Glucose tolerance
KW  - High-fat-sucrose-salt diet
KW  - Maternal folate treatment
KW  - Paternal programming
Y1  - 2018
U6  - https://doi.org/10.1007/s00125-018-4635-x
SN  - 0012-186X
SN  - 1432-0428
VL  - 61
IS  - 8
SP  - 1862
EP  - 1876
PB  - Springer
CY  - New York
ER  - 
TY  - JOUR
A1  - Li, Jian
A1  - Lu, Yong Ping
A1  - Reichetzeder, Christoph
A1  - Kalk, Philipp
A1  - Kleuser, Burkhard
A1  - Adamski, Jerzy
A1  - Hocher, Berthold
T1  - Maternal PCaaC38:6 is Associated With Preterm Birth - a Risk Factor for Early and Late Adverse Outcome of the Offspring
JF  - Journal of European public policy
N2  - Background/Aims: Preterm birth (PTB) and low birth weight (LBW) significantly influence mortality and morbidity of the offspring in early life and also have long-term consequences in later life. A better understanding of the molecular mechanisms of preterm birth could provide new insights regarding putative preventive strategies. Metabolomics provides a powerful analytic tool to readout complex interactions between genetics, environment and health and may serve to identify relevant biomarkers. In this study, the association between 163 targeted maternal blood metabolites and gestational age was investigated in order to find candidate biomarkers for PTB. Methods: Five hundred twenty-three women were included into this observational study. Maternal blood was obtained before delivery. The concentration of 163 maternal serum metabolites was measured by flow injection tandem mass spectrometry. To find putative biomarkers for preterm birth, a three-step analysis was designed: bivariate correlation analysis followed by multivariable regression analysis and a comparison of mean values among gestational age groups. Results: Bivariate correlation analysis showed that 2 acylcarnitines (C16:2, C2), 1 amino acids (xLeu), 8 diacyl-PCs (PCaaC36:4, PCaaC38:4, PCaaC38:5, PCaaC38:6, PCaaC40:4, PCaaC40:5, PCaaC40:6, PCaaC42:4), and 1 Acylalkyl-PCs (PCaeC40:5) were inversely correlated with gestational age. Multivariable regression analysis confounded for PTB history, maternal body mass index (BMI) before pregnancy, systolic blood pressure at the third trimester, and maternal body weight at the third trimester, showed that the diacyl-PC PCaaC38:6 was the only metabolite inversely correlated with gestational age. Conclusions: Maternal blood concentrations of PCaaC38:6 are independently associated with gestational age. (C) 2016 The Author(s) Published by S. Karger AG, Basel
KW  - Metabolomics
KW  - PCaaC38:6
KW  - Biomarker
KW  - Preterm birth
Y1  - 2016
U6  - https://doi.org/10.1159/000443428
SN  - 1420-4096
SN  - 1423-0143
VL  - 41
SP  - 250
EP  - 257
PB  - Karger
CY  - Basel
ER  - 
TY  - JOUR
A1  - Li, Jian
A1  - Chen, You-Peng
A1  - Wang, Zi-Neng
A1  - Liu, Tie-Bin
A1  - Chen, Dan
A1  - Dong, Yun-Peng
A1  - Hocher, Berthold
T1  - A functional fetal HSD11B2[CA]n microsatellite polymorphism is associated with maternal serum cortisol concentrations in pregnant women
JF  - Kidney & blood pressure research : official organ of the Gesellschaft für Nephrologie
N2  - Background/Aims: Cortisol plays an important role during pregnancy. It controls maternal glucose metabolism and fetal development. Cortisol metabolism is partially controlled by the 11b-HSD2. This enzyme is expressed in the kidney and human placenta. The activity of the enzyme is partially controlled by functional polymorphisms: the HSD11B2[CA]n microsatellite polymorphism. The impact of this functional gene polymorphism on cortisol metabolism and potential effects on the newborn's is unknown so far. Methods: In the current prospective birth cohort study in southern Asia, we analyzed the association of the HSD11B2[CA]n microsatellite polymorphisms in 187 mothers and their newborn's on maternal and newborn's serum cortisol concentrations. Results: Using multivariable regression analyses considering known confounding ( gestational age, newborn's gender, the labor uterine contraction states and the timing during the day of blood taking), we showed that the fetal HSD11B2[CA]n microsatellite polymorphisms in the first intron was related to maternal cortisol concentration ( R2=0.26, B=96.27, p=0.007), whereas as the newborn's cortisol concentrations were independent of fetal and maternal HSD11B2[CA] n microsatellite polymorphism. Conclusions: Our study showed for the first time that the fetal HSD11B2[CA]n microsatellite polymorphism of the HSD11B2 gene in healthy uncomplicated human pregnancy is associated with maternal cortisol concentration. This indicates that fetal genes controlling cortisol metabolism may affect maternal cortisol concentration and hence physiology in healthy pregnant women.
KW  - Pregnancy
KW  - Placenta
KW  - Cortisol vertical bar metabolism
KW  - 11 beta-hydroxysteroid dehydrogenase 2
KW  - HSD11B2[CA]n polymorphism
Y1  - 2013
U6  - https://doi.org/10.1159/000355761
SN  - 1420-4096
SN  - 1423-0143
VL  - 38
IS  - 1
SP  - 132
EP  - 141
PB  - Karger
CY  - Basel
ER  -