OBJECTIVETo explore the changes of serum leptin, soluble leptin receptor (SOB-R) concentrations and free leptin index (FLI) throughout the puberty in females, and estimate the effects of genetic and environmental factors on these indices.

METHODSThe population studied consists of 180 pairs of twins in 6 to 18 years old: 132 pairs of monozygotic twins and 48 pairs of dizygotic twins, who were all from Qingdao city, Shandong Province. Anthropometric and sexual characteristics were examined, fasting serum leptin and SOB-R contents were assayed by immunoradiometric assay and ELISA respectively.

RESULTSSerum leptin concentrations increased and SOB-R decreased throughout puberty (P < 0.05), brought out a sustained increase of FLI, especially in 7-9 and 12-14 years old (from 10.1 to 32.3 and 41.8 to 82.1 respectively); Leptin and FLI were positively, and SOB-R negatively correlated with morphological indices (correlation coefficients from 0.54 to 0.76, -0.23 to -0.42, respectively). Heritability of girl's serum leptin, SOB-R and FLI were 0.37, 0.84, 0.46 respectively.

CONCLUSIONSSerum free leptin index surge at 7-9 and 12-14 years old might be a predictor or trigger of the puberty onset and menarche, respectively; FLI might be determined by both genetic and environmental factors. Leptin should be substantially influenced by environment and reflect the fat mass of body compositions. SOB-R should be predominantly controlled by genetic factors yet. Genetic influence might be important in pubertal development and metabolic disorders.

Adolescent ; Child ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Immunoradiometric Assay ; Leptin ; blood ; Puberty ; blood ; Receptors, Leptin ; blood ; Twins, Dizygotic ; Twins, Monozygotic

Diseases in Twins ; Erythroblastosis, Fetal ; genetics ; Female ; Humans ; Infant, Newborn ; MNSs Blood-Group System ; immunology

OBJECTIVE: To delineate the blood group for a pair of twins with inconclusive ABO blood typing result. METHODS: Serological test for blood group was carried out by using ABO and Rh Blood Grouping Cards (Microcolumn Gel Immunoassay). Sequence specific primer-PCR (PCR-SSP), direct sequencing and TA clone sequencing were used to analyze the ABO gene. Genetic status was analyzed by using 16 short tandem repeat (STR) markers. RESULTS: Red blood cells of the twins displayed 2+ mixed agglutination phenomenon with anti-A, anti-A1 and anti-E. PCR-SSP and DNA sequencing of exons 6 to 7 revealed that they have an ABO*O.01.01/ABO*O.01.02 genotype. DNA sequencing of microsatellite enhancer region revealed presence of A gene. STR analysis revealed more than two haplotypes for 9 loci between the twins. After clustered by anti-A, the red blood cells were divided into two groups: A, CcDEe and O, CcDee, respectively. CONCLUSION Serological and molecular techniques have characterized the twins as blood group chimeras.
ABO Blood-Group System/genetics* ; Alleles ; Chimera/genetics* ; Genotype ; Humans ; Twins/genetics*

OBJECTIVE: To explore the DNA methylation sites correlated with blood pressure (systolic blood pressure, diastolic blood pressure, mean arterial pressure, pulse pressure) in adult twin population. METHODS: A total of 476 twins from the Chinese National Twin Registry were selected as the research population. Questionnaires were used to collect demographic characteristics, lifestyle, disease status and other information, and blood pressure, height, weight and other anthropometric indicators were measured. The genome-wide DNA methylation of whole blood samples was detected by using Infinium HumanMethylation450 BeadChip. The DNA methylation sites correlated with blood pressure were analyzed by constructing mixed effect model with adjusting potential confounding factors, and the significant level was false discovery rate <0.05. RESULTS: After data quality control, 465 twins (122 pairs of monozygotic twins, 104 pairs of dizygotic twins, 13 individuals from 13 pairs of twins) aged (44.8±13.2) years were finally enrolled. There were more males and more monozygotic twins, and the current smokers and current regular drinkers both accounted for more than 30%. No significant CpG site was found after multiple testing in the correlation study between genome-wide DNA methylation and blood pressure by using the collected twins. However, the cg07761116 located on chromosome 10 had low P value in the correlation analysis of 3 blood pressure indices (systolic blood pressure, diastolic blood pressure, mean arterial pressure), suggesting that this site might be correlated with blood pressure. The other 7 sites had low P value in the correlation analysis of the two blood pressure indices, respectively, which pointed to genes involved in neurological development, protein homeostasis, inflammatory reaction and other pathways. CONCLUSION There is no sufficient evidence to support any DNA methylation site correlated with blood pressure, which may be caused by insufficient sample size and other reasons. This study could provide a reference for subsequent similar twin studies, and subsequent studies can focus on the cg07761116 located on chromosome 10 and other sites with low P values.
Adult ; Blood Pressure ; Body Weight ; CpG Islands ; DNA Methylation ; Female ; Humans ; Male ; Middle Aged ; Twins, Monozygotic

Anti-HLA antibody related neonatal thrombocytopenia is an uncommon disorder caused by platelet antigen incompatibility between mother and fetus in Korea. Mothers who lack the specific platelet antigen produce the IgG against the platelet antigen which the fetus inherits from the father. These IgG antibodies are then transported across the placenta into the fetal circulation where they lead to the destruction of fetal platelets. We report a case of neonatal alloimmune thrombocytopenia related with anti-HLA antibody in second baby of dizygotic twin who had petechia on trunk and platelet count 43,000/mm. Initially, mother and twin showed the positives in antiplatelet antibodies. In microlym- phocytotoxic test at 6 months of age, anti-HLA antibodies was negative in twins but anti-HLA A2, A24 was positive in their mother. The patient was treated with intravenous immunoglobulin and clinically improved and her platelet count was norrnalized.
Acrocephalosyndactylia* ; Antibodies ; Blood Platelets ; Fathers ; Fetus ; Humans ; Immunoglobulin G ; Immunoglobulins ; Infant, Newborn ; Korea ; Mothers ; Placenta ; Platelet Count ; Thrombocytopenia, Neonatal Alloimmune ; Twins ; Twins, Dizygotic

Anti-HLA antibody related neonatal thrombocytopenia is an uncommon disorder caused by platelet antigen incompatibility between mother and fetus in Korea. Mothers who lack the specific platelet antigen produce the IgG against the platelet antigen which the fetus inherits from the father. These IgG antibodies are then transported across the placenta into the fetal circulation where they lead to the destruction of fetal platelets. We report a case of neonatal alloimmune thrombocytopenia related with anti-HLA antibody in second baby of dizygotic twin who had petechia on trunk and platelet count 43,000/mm. Initially, mother and twin showed the positives in antiplatelet antibodies. In microlym- phocytotoxic test at 6 months of age, anti-HLA antibodies was negative in twins but anti-HLA A2, A24 was positive in their mother. The patient was treated with intravenous immunoglobulin and clinically improved and her platelet count was norrnalized.
Antibodies ; Blood Platelets ; Fathers ; Fetus ; Humans ; Immunoglobulin G ; Immunoglobulins ; Infant, Newborn ; Korea ; Mothers ; Placenta ; Platelet Count ; Thrombocytopenia, Neonatal Alloimmune ; Twins ; Twins, Dizygotic

OBJECTIVETo study the contribution of genetic factors to the variance of serum leptin concentration in healthy, normotensive twins.

METHODSA total of 57 pairs of twins were investigated: 28 female and 19 male pairs of monozygotic(MZ) twins, and 6 female and 4 male pairs of dizygotic(DZ) twins. The zygosity of twins was determined by comparing the concordance of the genotype of nine fluorescence-labeled microsatellite markers. The genetic analysis was performed using the variance-based method. Serum leptin levels were determined in duplicate by a radioimmunoassay Kit (Linco Research, Inc., St. Charles, Missouri) as previously described.

RESULTSThe test of genetic variance revealed a significantly larger within-pair variance of serum leptin in the DZ twins, in comparison with the MZ twins. The corresponding heritability for serum leptin was 8%. Adjusted for BMI, gender, and uric acid (UA), the heritability for serum leptin was 0.18%. Log leptin correlated significantly with blood pressure (SBp r=0.355 P<0.001; DBp r=0.339 P<0.001). Stepwise multiple linear regression analysis revealed that only BMI, gender and UA were linked independently to serum leptin levels(R(2)=0.788, P<0.001).

CONCLUSIONThe above data indicate that environmental factors other than genetic factors are important determinants of leptinemia in normal subjects.

Adolescent ; Adult ; Body Mass Index ; Female ; Genotype ; Humans ; Leptin ; blood ; genetics ; Male ; Microsatellite Repeats ; genetics ; Middle Aged ; Twins, Dizygotic ; genetics ; Twins, Monozygotic ; genetics

OBJECTIVESTo study the contribution of the genes and environment to variation of serum levels of lipids and lipoprotein.

METHODSOne hundred and forty-three healthy monozygotic (MZ) twin pairs and 93 dizygotic (DZ) ones aged 5 to 19 [with a mean of (11.2 +/- 3.4) years]. Microsatellite polymorphism (STR) was used to diagnose zygosity of twins, and intraclass correlation coefficient method and Falconer formula were performed to investigate heritability of serum lipids and lipoproteins unadjusted or adjusted for age and sex. Logarithmic transformation was used for data with skewed distribution. Influence of relevant physical and biochemical indicators on serum lipids and other components was analyzed with partial coefficients of correlation adjusted for age and sex.

RESULTSIn the twin samples, difference in serum level of triglycerides (TG) between MZ and DZ was not statistically significant with intraclass variation and intraclass correlation. There was significant difference in serum levels of total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), and lipoprotein [Lp(a)] between MZ and DZ, with their heritability estimates of 0.56, 0.55, 0.49 and 0.58 unadjusted, respectively, and 0.63, 0.63, 0.55 and 0.64 adjusted for age and sex, respectively. Serum levels of TC, HDL-C, LDL-C and Lp(a) correlated reversely with age. Serum levels of TC, HDL-C and LDL-C in girls were slightly higher than those in boys. Most indicators for serum levels of lipids and lipoprotein, except for serum level of Lp(a) correlated with body mass index (BMI), body fat ratio, Pelidisi index, and other indexes such as blood pressure, blood sugar, serum level of calcium, adjusted for age and sex.

CONCLUSIONSSerum levels of TC, HDL-C and Lp(a) were influenced more greatly by genetic factors, and serum level of TG was mainly influenced by environmental ones. Levels of blood lipids in children were influenced by age and sex, and correlated with indicators that reflect their body fat and nutritional status.

Adolescent ; Adult ; Age Factors ; Child ; Cholesterol, HDL ; blood ; genetics ; Cholesterol, LDL ; blood ; genetics ; Female ; Humans ; Lipids ; blood ; genetics ; Lipoproteins ; blood ; genetics ; Male ; Sex Factors ; Triglycerides ; blood ; genetics ; Twin Studies as Topic ; Twins, Dizygotic ; Twins, Monozygotic

BACKGROUNDThe second-trimester maternal serum screening in twin pregnancy is still controversial, as the serum marker levels in twins are not as clear as those in singletons. This study aimed to evaluate the relationship between the levels of the second-trimester maternal serum free beta-human chorionic gonadotropin (free beta-HCG) and alpha-fetoprotein (AFP) in normal twin and singleton pregnancies and to estimate feasible analysis methods for utilizing these markers in second trimester screening for twin pregnancy.

METHODSOn the basis of a prospective population-based study of second-trimester maternal serum screening, the concentrations of maternal serum AFP and free beta-HCG of 195 normal twin pregnancy and 26,512 singleton controls at gestational weeks 15 to 20 were measured by time-resolved fluoroimmunoassay in one laboratory. The levels of markers were compared between the twins and singletons using weight-correction and gestational age-specific model.

RESULTSAccording to the research protocol, 95 communities were randomly sampled, which covered the whole Jiangsu province, the east of China. A total of 26 803 pregnant women (98%), from the target population accepted prenatal screening for maternal serum AFP, beta-HCG detection, and all babies were followed up for at least six months. There were 197 (0.73%) twin pregnancies, of which one case had fetal trisomy 18, and one case with fetal anencephaly. The others were normal twin pregnancy. From a total enrollment of 26 803 women participants, 26 512 women with normal singleton pregnancies were selected as the model controls. The other 291 pregnancies, including trisomy 21, neural tube defect (NTD), trisomy 18, and other fetal abnormalities, were excluded. No significant differences were found in the medians of gestational age-specific maternal serum free beta-hCG and AFP in normal twin pregnancy comparing with twice those in model controls with the exception of the medians for free beta-hCG during the 16th gestational week (P = 0.012).

CONCLUSIONThe weight-correction and gestational age-specific levels of Chinese Han population maternal serum free beta-hCG and AFP in normal twins were twice the levels as those in the singleton controls during the 17-19 gestational weeks.

Adult ; Chorionic Gonadotropin, beta Subunit, Human ; blood ; Female ; Humans ; Pregnancy ; blood ; Pregnancy Trimester, Second ; Twins ; alpha-Fetoproteins ; analysis

Jr(a) is a high-frequency antigen found in all ethnic groups. However, the clinical significance of the anti-Jr(a) antibody has remained controversial. Most studies have reported mild hemolytic disease of the newborn and fetus (HDNF) in Jr(a)-positive patients. Recently, fatal cases of HDNF have also been reported. We report the first case of HDNF caused by anti-Jr(a) alloimmunization in twins in Korea. A 33-yr-old nulliparous woman with no history of transfusion or amniocentesis was admitted at the 32nd week of gestation because of vaginal bleeding caused by placenta previa. Anti-Jr(a) antibodies were detected in a routine laboratory examination. An emergency cesarean section was performed at the 34th week of gestation, and 2 premature infant twins were delivered. Laboratory examination showed positive direct antiglobulin test and Jr(a+) phenotype in the red blood cells and the presence of anti-Jr(a) antibodies in the serum in both neonates. The infants underwent phototherapy for neonatal jaundice; this was followed by conservative management. They showed no further complications and were discharged on the 19th postpartum day. Preparative management to ensure the availability of Jr(a-) blood, via autologous donation, and close fetal monitoring must be performed even in cases of first pregnancy in Jr(a-) women.
Adult ; Blood Group Antigens/immunology ; *Blood Group Incompatibility ; Diseases in Twins/diagnosis/*immunology ; Erythroblastosis, Fetal/*diagnosis/immunology ; Female ; Gestational Age ; Humans ; Infant, Newborn ; Isoantigens/immunology ; Jaundice, Neonatal/complications/immunology/therapy ; Male ; Phenotype ; Phototherapy ; Pregnancy ; Pregnancy Complications, Hematologic/diagnosis/*immunology ; Twins