Jin Hoon Chung

Melatonin receptor 1 B polymorphisms associated with the risk of gestational diabetes mellitus

BackgroundsTwo SNPs in melatonin receptor 1B gene, rs10830963 and rs1387153 showed significant associations with fasting plasma glucose levels and the risk of Type 2 Diabetes Mellitus (T2DM) in previous studies. Since T2DM and gestational diabetes mellitus (GDM) share similar characteristics, we suspected that the two genetic polymorphisms in MTNR1B may be associated with GDM, and conducted association studies between the polymorphisms and the disease. Furthermore, we also examined genetic effects of the two polymorphisms with various diabetes-related phenotypes.MethodsA total of 1,918 subjects (928 GDM patients and 990 controls) were used for the study. Two MTNR1B polymorphisms were genotyped using TaqMan assay. The allele distributions of SNPs were evaluated by x2 models calculating odds ratios (ORs), 95% confidence intervals (CIs), and corresponding P values. Multiple regressions were used for association analyses of GDM-related traits. Finally, conditional analyses were also performed.ResultsWe found significant associations between the two genetic variants and GDM, rs10830963, with a corrected P value of 0.0001, and rs1387153, with the corrected P value of 0.0008. In addition, we also found that the two SNPs were associated with various phenotypes such as homeostasis model assessment of beta-cell function and fasting glucose levels. Further conditional analyses results suggested that rs10830963 might be more likely functional in case/control analysis, although not clear in GDM-related phenotype analyses.ConclusionThere have been studies that found associations between genetic variants of other genes and GDM, this is the first study that found significant associations between SNPs of MTNR1B and GDM. The genetic effects of two SNPs identified in this study would be helpful in understanding the insight of GDM and other diabetes-related disorders.

Soluble endoglin and transforming growth factor‐β1 in women who subsequently developed preeclampsia

This study aimed to analyze the differences of soluble endoglin (sEng) and transforming growth factor‐beta1 (TGF‐β1) according to preeclamptic complications and to investigate the correlation between these factors and the clinical symptoms of preeclampsia.

Non-Invasive Epigenetic Detection of Fetal Trisomy 21 in First Trimester Maternal Plasma

Background Down syndrome (DS) is the most common known aneuploidy, caused by an extra copy of all or part of chromosome 21. Fetal-specific epigenetic markers have been investigated for non-invasive prenatal detection of fetal DS. The phosphodiesterases gene, PDE9A, located on chromosome 21q22.3, is completely methylated in blood (M-PDE9A) and unmethylated in the placenta (U-PDE9A). Therefore, we estimated the accuracy of non-invasive fetal DS detection during the first trimester of pregnancy using this tissue-specific epigenetic characteristic of PDE9A. Methodology/Principal Findings A nested, case-control study was conducted using maternal plasma samples collected from 108 pregnant women carrying 18 DS and 90 normal fetuses (each case was matched with 5 controls according to gestational weeks at blood sampling). All pregnancies were singletons at or before 12 weeks of gestation between October 2008 and May 2009. The maternal plasma levels of M-PDE9A and U-PDE9A were measured by quantitative methylation-specific polymerase chain reaction. M-PDE9A and U-PDE9A levels were obtained in all samples and did not differ between male and female fetuses. M-PDE9A levels did not differ between the DS cases and controls (1854.3 vs 2004.5 copies/mL; P = 0.928). U-PDE9A levels were significantly elevated in women with DS fetuses compared with controls (356.8 vs 194.7 copies/mL, P<0.001). The sensitivities of U-PDE9A level and the unmethylation index of PDE9A for non-invasive fetal DS detection were 77.8% and 83.3%, respectively, with a 5% false-positive rate. In the risk assessment for fetal DS, the adjusted odds ratios of U-PDE9A level and UI were 46.2 [95% confidence interval: 7.8–151.6] and 63.7 [95% confidence interval: 23.2–206.7], respectively. Conclusions Our findings suggest that U-PDE9A level and the unmethylation index of PDE9A may be useful biomarkers for non-invasive fetal DS detection during the first trimester of pregnancy, regardless of fetal gender.

Gestational weight gain is an important risk factor for excessive fetal growth

Objective To estimate the odds ratio of prepregnant body mass index (BMI), gestational weight gain (GWG), and gestational diabetes mellitus (GDM) for excessive fetal growth, which we define as large for gestational age (LGA). Methods We included 16,297 women who delivered a live-born singleton baby at term. We fit logistic regressions to estimate the odds ratios of variables, including maternal age, parity, prepregnant BMI ≥23, GWG ≥15 kg, and GDM, for LGA. We classified GWG into four categories (<10, 10-14.9, 15-19.9, and ≥20 kg) and BMI into four categories (underweight, normal, overweight, and obese). After adjusting for age and parity, we analyzed the odds ratios of prepregnant BMI according to GWG between non-GDM and GDM women for LGA. Results The odds ratios of GWG ≥15 kg and prepregnancy BMI ≥23 for LGA were 2.40 (95% confidence interval [CI], 2.16-2.67) and 2.24 (95% CI, 1.99-2.51), respectively. The odd ratio of GDM was 1.37 (95% CI, 1.09-1.71). The risk of GDM women with normal/-overweight BMI and GWG <15 kg for LGA was not significantly greater than those of the reference group. The odd ratios of GDM women with overweight/obese BMI and GWG 15 to 19.9 kg were 3.95 (95% CI, 1.26-12.38) and 9.70 (95% CI, 3.79-24.87), respectively. Conclusion GWG ≥15 kg might be a more important risk factor for LGA than either prepregnancy BMI ≥23 or GDM. Risk for LGA was highest in obese GDM women with GWG ≥15 kg.

Exposure to Amlodipine in the First Trimester of Pregnancy and During Breastfeeding

Objective: To assess the fetal outcome of three hypertensive women exposed to amlodipine. 5 mg/day, in the first trimester of pregnancy. Case 1: The patient was treated with amlodipine until 7 weeks of gestation. She was also exposed to levosulpiride, aluminum hydroxide gel, magnesium carbonate, and Ginkgo biloba. At 38+3 weeks of pregnancy, she delivered a 3750 g healthy female baby, and restarted taking amlodipine, 5 mg/day, while exclusively breastfeeding her daughter. At three months of age, the infant was healthy. Case 2: The patient was treated with amlodipine from 2+2 to 3+4 weeks of pregnancy. Her treatment was modified to atenolol until the week 6+4 weeks, when she declined any antihypertensive treatment. At 39+4 weeks of pregnancy, the patient delivered a 2600 g baby. At 20 months old, the baby presented with intellectual delay and weakness in the left arm and hand grasp. These neurological alterations were not attributed to her exposure to amlodipine early in utero. Case 3: The patient was treated with amlodipine from 7+6 to 12 weeks of pregnancy. She was also taking sucralfate and lorazepam. At 12 weeks of amenorrhea, ultrasound revealed a 15.3 mm, single fetal pole in the gestational sac without cardiac activity. She underwent dilatation and evacuation of a dead embryo. Conclusion: As reported with other calcium-channel blockers, amlodipine does not appear to be teratogenic and it appears to be compatible with breastfeeding.

Outcomes of subsequent pregnancies after uterine compression sutures for postpartum hemorrhage.

OBJECTIVE: To estimate the association between uterine compression sutures for postpartum hemorrhage and subsequent pregnancy outcomes. METHODS: We reviewed the medical records of 336 women who received uterine compression sutures to control postpartum hemorrhage during their first delivery at a single medical center between 2006 and 2011. Of these, 42 women who became pregnant again and received care through our hospital were included in this study. One hundred thirty-nine pregnant women matched for age and parity who did not receive uterine compression sutures during a previous cesarean delivery served as the control group. We compared subsequent pregnancy outcomes and operative findings during repeat cesarean delivery between the two groups. RESULTS: There were four (9.5%) miscarriages and one (2.4%) tubal pregnancy in the compression suture group compared with 14 (10.1%) miscarriages and two (1.5%) tubal pregnancies in the control group (P=.92 and P=.68, respectively). In the compression suture group, 34 (81.0%) women delivered at term and two (4.7%) women had preterm deliveries. In the control group, 114 (82.0%) women delivered at term and seven (5.0%) women had preterm deliveries (P=.88 and P=.60, respectively). The rate of pelvic adhesions on repeat cesarean delivery was significantly higher in the compression suture group than in the control group (34.3% compared with 17.5%, P=.03). CONCLUSIONS: Subsequent pregnancy outcomes were similar for women who did and those who did not receive uterine compression sutures during their prior delivery, whereas uterine adhesions at repeat cesarean delivery were more prevalent in women who received uterine compression sutures. LEVEL OF EVIDENCE: II

Clinical characteristics and outcomes of antenatal fetal intra-abdominal umbilical vein varix detection

Objective This study reviewed clinical characteristics of fetal intra-abdominal umbilical vein (FIUV) varices that were detected during antenatal ultrasound examinations. Methods Between January 2006 and January 2012, 121 cases of FIUV varices were detected and 7 cases were lost to follow-up. We retrospectively reviewed the medical records of 114 patients and neonates. Results From a total 96,553 ultrasound examinations in 43,995 pregnancies, 121 cases of FIUV varices were identified (2.8 per 1,000 pregnancies). Gestational age at diagnosis was 32.0 ± 2.9 weeks (range, 20.1-36.3 weeks), the mean diameter of the FIUV varix was 12.6 ± 2.1 mm (range, 8.0-21.0 mm) at initial diagnosis and the mean maximal diameter was 13.1 ± 2.3 mm (range, 8.0-21.0 mm) during follow-up. The most severe pregnancy complications included one case of intrauterine fetal death and another case of fetal hydrops. Associated fetal anomalies (n = 11, 9.6%) detected by ultrasonography included bilateral renal pelvis dilatation, ventriculomegaly, cryptorchidism, incomplete renal duplication and pulmonary sequestration. A total of 104 cases (91.2%) were delivered at term and 10 cases (8.8%) were preterm deliveries before 37 weeks of gestation. Conclusion FIUV varices that are not associated with fetal anomalies based on ultrasound examination during prenatal care have favorable pregnancy outcomes. Nevertheless, close fetal monitoring is recommended to decrease perinatal complications.

Association between genetic polymorphisms in androgen receptor gene and the risk of preeclampsia in Korean women

PurposeTo investigate associations between the androgen receptor (AR) polymorphisms as CAG repeats, GGC repeats and c.211G>A polymorphism and the risk of preeclampsia.MethodsThe AR polymorphisms were experienced in 184 preeclamptic patients and 190 normal pregnancies and analyzed by multiple logistic regression.ResultsWomen with GGC repeats>16 were more frequently observed in preeclampsia, compared to those with GGC repeats≤16 [adjOR (95% CI): 3.64 (1.71–6.23)]. However, no significant differences were observed between the two groups with respect to CAG repeats. The genotypic and allelic frequencies of c.211G>A variant were significantly higher in cases than in controls (P < 0.05 for both). In the combined distribution of these polymorphisms, the highest risk of preeclampsia was found among women with the haplotype as CAG > 20/GA/GGC>16 [adjOR (95% CI): 4.26 (1.92–12.23)].ConclusionsOur findings suggest that longer GGC repeats and c.211G>A variant in the AR gene are associated with increased susceptibility to the risk of preeclampsia.

Determination of the carrier frequencies of selected GJB2 mutations in the Korean population.

Abstract Objective: Mutations in the GJB2 gene are a major cause of hereditary hearing loss. However, only a few studies have investigated carrier frequencies of GJB2 mutations in the general population. The aim of this study was to estimate the carrier frequencies of three GJB2 mutations, including 235delC, V37I, and G45E, in the general Korean population. Design: A standard questionnaire of self-reported hearing loss was used to identify and recruit subjects. Screening for three mutations was performed using an allele-specific polymerase chain reaction (PCR), PCR-restriction fragment length polymorphism, and direct DNA sequencing. Study sample: A total of 1256 unrelated healthy individuals were analysed in the present study. Results: Of the 1256 individuals, 24 had GJB2 mutations; 11 were found to be heterozygous for 235delC, 11 were heterozygous and one was homozygous for V37I, and one was heterozygous for G45E. One individual had a compound heterozygous mutation of 235delC/V37I. The allele frequencies of 235delC, V37I, and G45E mutations were 0.44%, 0.52%, and 0.04%, respectively. The carrier frequency of either the 235delC or V37I mutation was estimated to be 0.88% with 95% binomial CI, 0.44–1.56. Conclusions: These results will facilitate diagnosis of, and genetic counseling for, hearing loss in Koreans. Sumario Objetivo: Las mutaciones del gene GJB2 son una causa muy importante de pérdidas auditivas hereditarias. No obstante, solamente pocos estudios han investigado las frecuencias portadoras de las mutaciones del GJB2 en la población general. El objetivo de este estudio fue estimar las frecuencias portadoras de tres mutaciones del GJB2, incluyendo la 235delC, V37I y G45E, en la población general de Corea. Diseño: Se utilizó un cuestionario estándar de pérdida auditiva auto-reportada para identificar y reclutar sujetos. El tamiz de las tres mutaciones se realizó usando una reacción en cadena de la polimerasa alelo-específica (PCR), el polimorfismo de los fragmentos de restricción PCR y la secuenciación directa de DNA. Muestra de estudio: Se analizaron en este estudio 1,256 individuos sanos, no relacionados, (sanos en este estudio). Resultados: De los 1,256 individuos, 24 tenían mutaciones del GJB2; 11 se encontraron como heterocigóticos para el 235delC, 11 fueron heterocig ticos y uno fue homocigótico para V37I y uno fue heterocigótico para G45E. Un individuo tenía una mutación heterocigótica compuesta del 235delC/V37I. Las frecuencias de las mutaciones del alelo de 235delC, V37I, y G45E fueron del 0.44%, 0.52%, y 0.04%, respectivamente. La frecuencia portadora de las mutaciones tanto del 235delC como del V37I se estimó en 0.88%, con CI binomial del 95% de 0.44-1.56. Conclusiones: Estos resultados facilitarán el diagnóstico y el asesoramiento genético en casos de pérdida auditiva en la población de Corea.

Pregnancy outcome of women inadvertently exposed to ribostamycin during early pregnancy: a prospective cohort study.

No information is currently available on the safety of the aminoglycoside ribostamycin in pregnancy. We aimed to study the pregnancy outcome of women inadvertently exposed to ribostamycin during the first trimester of pregnancy. In a prospective cohort study, 102 women inadvertently exposed to ribostamycin during the first trimester of pregnancy and an age- and gravidity-matched control group, were enrolled. Study outcomes were gestational age at birth, major and minor malformations, and birth weight. Fetal outcomes were evaluated in 85 women inadvertently exposed to ribostamycin during the first-trimester of pregnancy and in 170 control subjects. Newborns were clinically examined at birth by a neonatologist and by imaging studies if any suspicious abnormalities were noted. There were 4/85 (4.9%) babies born with major malformations in the exposed group and 3/170 (1.8%) in the control group (P=0.7). Gestational age at delivery, rate of minor anomalies, rate of preterm births, and birth weight were not different between groups. In conclusion, similar to what is reported for other aminoglycoside, exposure to ribostamycin during the first-trimester of pregnancy does not appear to increase the risk of adverse fetal outcomes.