Suicidal ideation in adolescents with adiponectin receptor 2 rs12342 polymorphism affected by Wenchuan earthquake.

PURPOSE: The present study was to investigate prevalence of suicidal ideation and its associations with biological and environmental factors in adolescents with different genotypes of rs12342 at adiponectin receptor 2 gene (ADIPOR2). METHODS: Suicidal ideation, biological and environmental factors were evaluated by questionnaires in 669 high school students after Wenchuan earthquake in China. ADIPOR2 rs12342 was genotyped by polymerase chain reaction-restriction fragment length polymorphism and verified by DNA sequencing. RESULTS: Female adolescents had higher prevalence of suicidal ideation than male students in AG heterozygote and GG homozygote, but not AA homozygote. Prevalence of suicidal ideation was different in male, but not female, subjects with different genotypes. Genotype and allele frequencies were significantly different between male students with and without suicidal ideation, but not the female counterparts. Family history of mental disorders, extent of damage to property, carbohydrate intake and protein intake were associated with suicidal ideation in female subjects, while ADIPOR2 rs12342, father's educational level and previous trauma experience were associated with suicidal ideation in male subjects. CONCLUSION: ADIPOR2 rs12342 is associated with and has potential to interact with environmental factors on suicidal ideation in a gender-dependent manner in youth. These findings pave a novel way and perspective for precision inferences of suicidal ideation in subjects with different genetic backgrounds. ADIPOR2 rs12342 needs to be considered when intervening suicidal ideation, especially in adolescents.

Reduced hepatic AdipoR2 by increased glucocorticoid mediates effect of psychosocial stress to elevate serum cholesterol.

Understanding the effects of psychosocial stress on serum cholesterol may offer valuable insights into the relationship between psychological disorders and endocrine diseases. However, these effects and their underlying mechanisms have not been elucidated yet. Here we show that serum corticosterone, total cholesterol and low-density lipoprotein cholesterol (LDL-C) are elevated in a mouse model of psychosocial stress. Furthermore, alterations occur in AdipoR2-mediated AMPK and PPARα signaling pathways in liver, accompanied by a decrease in LDL-C clearance and an increase in cholesterol synthesis. These changes are further verified in wild-type and AdipoR2 overexpression HepG2 cells incubated with cortisol and AdipoR agonist, and are finally confirmed by treating wild-type and hepatic-specific AdipoR2 overexpression mice with corticosterone. We conclude that increased glucocorticoid mediates the effects of psychosocial stress to elevate serum cholesterol by inhibiting AdipoR2-mediated AMPK and PPARα signaling to decrease LDL-C clearance and increase cholesterol synthesis in liver.

Association between PEMT rs7946 and blood pressure levels in Chinese adolescents.

OBJECTIVES: This study was to explore blood pressure levels in Chinese adolescents with different genotypes of phosphatidylethanolamine N-methyltransferase (PEMT) gene ( PEMT ) rs7946, as well as effects of dietary intake on blood pressure levels with different genders and different genotypes of PEMT rs7946. METHODS: PEMT rs7946 genotypes were identified by PCR-restriction fragment length polymorphism and verified by DNA sequencing. Blood pressure was measured using a standard mercury sphygmomanometer. Dietary intakes were analyzed based on a 3-day diet diary, and dietary components were calculated using computer software. RESULTS: A total of 721 high school students (314 males and 407 females) at the age of 16.86 ±â€…0.59 years were included. The A allele carriers of PEMT rs7946 had increased levels of SBP, DBP, mean arterial pressure (MAP) and pulse pressure (PP) than the GG homozygotes in the female subjects. There were significant interactions between PEMT rs7946 and gender on SBP and MAP levels, regardless of whether an unadjusted or adjusted model was used. When dietary intake was taken into account, fat intake was positively associated with SBP and PP in the male GG homozygotes, while protein intake was positively associated with PP in the female A allele carriers of PEMT rs7946. CONCLUSION: This study suggests that PEMT rs7946 is significantly associated with blood pressure levels in human being. There might be interactions among PEMT rs7946, gender, and dietary intake on blood pressure levels in the adolescent population.

Associations of TNF-RII rs1061622 With Post-Traumatic Stress Disorder and Their Interplays on Serum Lipids Levels in Adolescents.

OBJECTIVE: To verify effects of rs1061622 at tumor necrosis factor-α receptor II (TNF-RII) gene (TNF-RII) on post-traumatic stress disorder (PTSD) and its interactive effects with PTSD on serum lipids levels in adolescents. METHODS: PTSD was measured by PTSD Checklist-Civilian Version (PCL-C) in 699 adolescent survivors at 6 months after Wenchuan earthquake in China. A polymerase chain reaction and restriction fragment length polymorphism assay were utilized for TNF-RII rs1061622 genotyping followed by verification using DNA sequencing. Serum triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol were tested using routine methods. RESULTS: G (deoxyguanine) allele carriers had higher PCL-C scores than TT (deoxythymidine) homozygotes in female subjects. Female adolescents had higher PCL-C scores than male subjects in TT homozygotes. Predictors of PTSD prevalence and severity were different between G allele carriers and TT homozygotes. Subjects with PTSD had lower TG, TG/HDL-C, TC/HDL-C, and higher HDL-C than adolescents without PTSD in male G allele carriers. G allele carriers had higher TG/HDL-C and TC/HDL-C than TT homozygotes in male adolescents without PTSD, and lower TG and TG/HDL-C in male PTSD patients. G allele carriers had higher TG than TT homozygotes only in female adolescents without PTSD. CONCLUSION: These results suggest reciprocal actions of TNF-RII rs1061622 with other factors on PTSD severity, interplays of TNF-RII rs1061622 with PTSD on serum lipid levels, and novel treatment strategies for PTSD and comorbidities of PTSD with hyperlipidemia among adolescents with different genetic backgrounds of TNF-RII rs1061622 after experiencing traumatic events.

The Waist-Hip Ratio is a Mediator Between Serum Levels of Brain-Derived Neurotrophic Factor and Its Val66Met Polymorphism in Adolescents.

Aim: To explore anthropometric, metabolic and dietary factors associated with and their interplays with the Val66Met polymorphism at brain-derived neurotrophic factor (BDNF) gene (Bdnf) on serum BDNF levels in adolescents. Methods: Serum BDNF levels were quantified using an enzyme-linked immunosorbent assay in 644 high school students (278 males/366 females). A polymerase chain reaction and restriction fragment length polymorphism assay were utilized for Bdnf Val66Met genotyping followed by verification using DNA sequencing. Serum levels of metabolic characteristics were assayed by routine methods. The intake of macro and micronutrients was collected by a three-day food record. Results: Serum BDNF levels were found to be significantly different in the subjects with different genotypes of Bdnf Val66Met (Val/Val homozygotes, 60.05 ± 28.07 ng/mL vs Val/Met heterozygotes, 56.37 ± 29.34 ng/mL vs Met/Met homozygotes, 51.32 ± 24.54 ng/mL, p = 0.022). Among the 36 tested variables, waist-hip ratio (WHR) (ß = -0.163, p < 0.001), iodine intake (ß = 0.132, p = 0.001), heart rate (ß = 0.108, p = 0.005), high-density lipoprotein cholesterol (HDL-C) (ß = 0.098, p = 0.011) and dietary fiber intake (ß = 0.082, p = 0.084) were the predictor of serum BDNF levels, while SBP (ß = 0.097, p = 0.013) and WHR (ß = 0.091, p = 0.021) were related with Bdnf Val66Met. Moreover, WHR was observed to play a partial mediating role in the relationship between Bdnf Val66Met and serum BDNF levels (95% CI [-1.161, -0.087]) and contribute 13.05% of its total effect on serum BDNF levels. Conclusion: There are interplays between WHR and Bdnf Val66Met on serum BDNF levels, which may be among the explanations for the previous heterogeneous reports and provide novel insights into the regulation of serum BDNF levels.

Serum Levels of Free Fatty Acids in Obese Mice and Their Associations with Routine Lipid Profiles.

PURPOSE: To investigate serum levels of free fatty acids (FFAs) and their associations with routine serum lipids in diet-induced obese mice, which have been scantily reported before. METHODS: Male C57BL/6 J mice were fed high-fat diets for 12 weeks to induce obesity. Levels of serum FFAs were measured by ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry. RESULTS: Obese mice had higher serum levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), but lower triglycerides (TG) than control mice. A total of 30 FFAs were found, and 3 saturated fatty acids (SFAs), all 8 monounsaturated fatty acids (MUFAs) and 7 polyunsaturated fatty acids (PUFAs) decreased in obese mice, but one SFA (C4:0) increased. Differences in the relative levels of individual FFAs to total FFAs, SFAs, MUFAs or PUFAs between obese and control mice were different from each other and from those evaluated by concrete levels except C4:0, C16:1, C19:1 and C18:4. Only the concrete levels of C4:0, C22:3 and C18:4 were associated with routine serum lipids, including C22:3 negatively with TG in control mice, and C4:0 and C18:4 positively with LDL-C in obese mice, although the relative levels of C4:0 to total MUFAs negatively with TC, and C23:3 to total SFAs or MUFAs negatively with TG in control mice. Different relative levels of the remaining FFAs were differently associated with different routine serum lipids in obese and/or control mice. CONCLUSION: Obesity may influence serum FFAs profiles. The relationship of individual FFAs and their relative levels to other FFAs with routine serum lipids in obese and control mice suggests that individual FFAs may interact with others and obesity on levels of routine serum lipids. Once confirmed, the interactions may be novel perspectives when fatty acids are used to improve hyperlipidemia in the subjects with obesity.

Polymerase chain reaction-based assays facilitate the breeding and study of mouse models of Klinefelter syndrome.

Klinefelter syndrome (KS) is one of the most frequent genetic abnormalities and the leading genetic cause of nonobstructive azoospermia. The breeding and study of KS mouse models are essential to advancing our knowledge of the underlying pathological mechanism. Karyotyping and fluorescence in situ hybridization are reliable methods for identifying chromosomal contents. However, technical issues associated with these methods can decrease the efficiency of breeding KS mouse models and limit studies that require rapid identification of target mice. To overcome these limitations, we developed three polymerase chain reaction-based assays to measure specific genetic information, including presence or absence of the sex determining region of chromosome Y (Sry), copy number of amelogenin, X-linked (Amelx), and inactive X specific transcripts (Xist) levels. Through a combined analysis of the assay results, we can infer the karyotype of target mice. We confirmed the utility of our assays with the successful generation of KS mouse models. Our assays are rapid, inexpensive, high capacity, easy to perform, and only require small sample amounts. Therefore, they facilitate the breeding and study of KS mouse models and help advance our knowledge of the pathological mechanism underlying KS.

Male adolescents with Interleukin 10 rs1800872 AA genotype had higher prevalence and slower recoveries of post-traumatic stress disorder at late stage of a follow-up.

BACKGROUND: Pathophysiological mechanisms of post-traumatic stress disorder (PTSD) are elusive and heterogeneous relationships have been reported among PTSD, Interleukin 10 (IL-10), and other factors after stresses. The present study aimed to longitudinally investigate associations of PTSD with environmental factors and genetic variation of rs1800872 at IL-10 gene. METHODS: Symptoms of PTSD were measured by PTSD Checklist-Civilian Version (PCL-C) in 462 high school students at 6, 12, and 18 months after Wenchuan earthquake in China. Genotypes of IL-10 rs1800872 were identified by polymerase chain reaction-restriction fragment length polymorphism analysis and verified by DNA sequencing. RESULTS: AA homozygotes had higher PTSD prevalence than C allele carriers only at 18 months in male, but not female subjects. PTSD prevalence at 18 months was lowered in all subjects except male AA homozygotes when compared to that at 6 months, and only in female C allele carriers when compared to that at 12 months. PCL-C scores at 18 months were decreased in all students but not in male AA homozygotes when compared to those at 6 months. IL-10 rs1800872 was associated with PTSD at 18 months. Patterns of predictors of PCL-C scores were different between AA homozygotes and C allele carriers at different times during the follow-up. CONCLUSION: There were different reciprocal actions of IL-10 rs1800872 with other potential factors or predictors on PTSD in a time-course and gender-dependent manner. Male students with IL-10 rs1800872 AA genotype had higher prevalence and slower recoveries of PTSD at late stage of the follow-up, suggesting requirements of special psychiatric care or drug supplementation at this stage.

Insertion/deletion polymorphism at angiotensin-converting enzyme gene in PTSD individuals and their reciprocal effects on blood pressure.

OBJECTIVES: The aim of the present study was to investigate relationships between insertion/deletion (I/D) polymorphism at angiotensin-converting enzyme gene (ACE) and post-traumatic stress disorder (PTSD), as well as their interactions on blood pressure. METHODS: Variants of ACE I/D were identified by polymerase chain reaction method and verified by DNA sequencing. PTSD symptoms were assessed by the PTSD Checklist-Civilian Version (PCL-C) based on DSM-IV-TR criteria among high school students at 6 months after the 2008 Wenchuan earthquake. RESULTS: Female subjects were found to have higher prevalence of PTSD and PCL-C scores than male counterparts in the II homozygotes (p = .038 for PTSD and p = .003 for PCL-C scores) and the ID heterozygotes (p = .000 for PTSD and p = .000 for PCL-C scores), but not in the DD homozygotes. Male subjects with the ID (p = .046) or the DD genotype (p = .039) had lower pulse pressure (PP) than the male II homozygotes, while the female II homozygotes had lower diastolic blood pressure (DBP) than the female DD homozygotes (p = .036). ACE I/D, PTSD, or PCL-C scores, as well as gender and BMI, were found to be the predictors of PP. CONCLUSIONS: These results indicate that there are interactions of ACE I/D and PTSD, together with gender and BMI, on PP. This finding may be the additional explanation for the heterogeneous relationships between PTSD and blood pressure, and suggest psychiatry care and different medication strategies for patients with comorbidities of PTSD and hypertension and with different genotypes of ACE I/D.

Depression Augments Plasma APOA4 without Changes of Plasma Lipids and Glucose in Female Adolescents Carrying G Allele of APOA4 rs5104.

The association of apolipoprotein AIV (APOA4) with depression or plasma levels of lipids and glucose has been inconsistently reported. However, interplays between APOA4 and depression on the levels have not been explored yet. The present study aimed to investigate plasma levels of APOA4, lipids, and glucose in adolescents with different genotypes of APOA4 rs5104 and with or without depression. Depressive symptoms were assessed in 631 adolescents by Beck Depression Inventory (BDI). A total score of 14 was defined as the cutoff point for depression. Plasma levels of triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), glucose, and insulin were measured by routine methods, and APOA4 by enzyme-linked immunosorbent assays. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism analyses and verified by DNA sequencing. Female adolescents had higher prevalence of depression than male subjects only in G allele carriers (p = 0.015), but not in AA homozygotes. Risk factors of depression and predictors of depression severity were different between G allele carriers and AA homozygotes. Lower levels of glucose (p = 0.003) were observed in male G allele carriers than those in male AA homozygotes and increased TG levels (p = 0.008) in female G allele carriers when compared with those in female AA homozygotes. When both APOA4 rs5104 and depression were taken into account, subjects with depression had higher levels of plasma APOA4 than adolescents without depression only in female G allele carriers (p = 0.043), but no significant changes of plasma lipids and glucose. Depression augments plasma APOA4 levels without changes of plasma lipids and glucose in female adolescents carrying G allele of APOA4 rs5104. These results may provide a novel explanation for the inconsistent relationship between depression, APOA4, and plasma levels of lipids and glucose in the literature.

Increased TG/HDL-C in female G allele carriers of rs1061622 at gene of tumour necrosis factor receptor 2 with suicidal ideation.

BACKGROUND: Relationships between tumour necrosis factor receptor 2 (TNF-RII), suicidal ideation and levels of serum lipids have not been reported yet. The present study was to explore lipids profiles in Chinese adolescents with different genotypes of TNF-RII rs1061622 and with or without suicidal ideation. METHODS: Dietary intakes were surveyed by questionnaires. TNF-RII rs1061622 genotypes were examined by polymerase chain reaction restriction-fragment length polymorphism and verified by DNA sequencing. Lipids levels were examined by routine methods. RESULTS: Higher TC/HDL-C levels were observed in the subjects with suicidal ideation than those without suicidal ideation in the male students, but no significant differences were found in the female counterparts. When both TNF-RII rs1061622 and suicidal ideation were considered, although there was no significant difference of suicidal ideation prevalence between the TT homozygotes and the G allele carriers, the G allele carriers had elevated levels of TG and TG/HDL-C compared with the TT homozygotes only in the female subjects with suicidal ideation. The subjects with suicidal ideation had higher TG/HDL-C levels than those without suicidal ideation only in the female G allele carriers. Both suicidal ideation and TNF-RII rs1061622, together with BMI, gender and fat intakes, were found the predictors of TG/HDL-C levels. Different relationship patterns of lipids levels were discovered between male and female subjects with different genotypes and with or without suicidal ideation. CONCLUSIONS: Different changes of lipids profiles between the subjects with or without suicidal ideation may result from not only the genders, but also their interactions with TNF-RII rs1061622.

Effects of earthquake and related environmental factors on relationship of posttraumatic stress disorder with LDLR rs5925.

To test the relationship not yet explored before among earthquake and related environmental factors, low-density lipoprotein receptor (LDLR) and posttraumatic stress disorder (PTSD), the genetic variation of LDLR rs5925 was selected and PTSD was examined by PTSD Checklist-Civilian Version (PCLC) in adolescents with different genotypes of LDLR rs5925 longitudinally at 6, 12 and 18 months after the 2008 Wenchuan earthquake. The C allele carriers were observed to have higher PTSD prevalence than the TT homozygotes in the male subjects, and higher PTSD prevalence and PCL-C scores in the female subjects only at 6 months. When compared to that at 12 months, decreased PTSD prevalence was observed at 18 months only in the female C allele carriers, but not in the female TT homozygotes or the male subjects. The potential risk factors of PTSD and predictors of PCL-C scores were different during the follow-up. LDLR rs5925 was one of the predictors for PCL-C scores at 6 and 12 months, and one of the potential factors for PTSD prevalence at 6 months. These results suggest that interactions may occur between earthquakes and other related environmental factors, which could affect the relationship of LDLR rs5925 with PTSD and be considered for individualized treatment.

The Leptin Gene rs7799039 Modulates the Prevalence of Posttraumatic Stress Disorder After an Earthquake in Han Chinese Adolescents.

OBJECTIVES: The study's aim was to examine the prevalence and severity of posttraumatic stress disorder (PTSD) longitudinally among high school students with different genotypes of the leptin gene (LEP) rs7799039 after the 2008 Wenchuan earthquake in China. METHODS: The symptoms of PTSD were measured by the PTSD Checklist-Civilian Version (PCL-C) based on DSM-IV-TR criteria in 462 students at 6, 12, and 18 months after the earthquake. The genotypes of LEP rs7799039 were identified by polymerase chain reaction-restriction fragment length polymorphism analyses in 2018 using genomic DNA prepared in 2008 and stored at -80°C and verified by DNA sequencing. The association of LEP genotypes with PTSD was then analyzed by various statistical methods. RESULTS: The AA homozygotes had higher prevalence of PTSD than the G allele carriers at 12 months (22.30% vs 10.53%, P = .013) and higher median (interquartile range [IQR]) PCL-C scores at 12 (27.00 [24.00-35.75] vs 26.00 [22.00-31.25], P = .010) and 18 months (27.00 [21.00-32.00] vs 24.00 [19.00-29.00], P = .003) post-earthquake among female subjects. Female students had higher PCL-C scores than male subjects at 6 and 12 months regardless of the genotypes but only among the AA homozygotes at 18 months (27.00 [21.00-32.00] vs 22.00 [18.00-26.00], P = .000). The potential risk factors for and predictors of PTSD severity differed at different time points during follow-up. LEP rs7799039 was a potential factor for PTSD at 12 months and a predictor of PTSD severity at 18 months post-earthquake. CONCLUSIONS: An association of LEP rs7799039 with the prevalence and severity of PTSD in Chinese adolescents was observed. These results indicate that females with the LEP rs7799039 AA genotype had more severe PTSD characteristics compared to female G allele carriers, suggesting that psychosocial or pharmacologic managements may particularly be needed by these female subjects.

Posttraumatic Stress Disorder Augments Plasma Triglycerides in TT Homozygotes of rs495225 at Growth Hormone Secretagogue Receptor Gene.

Posttraumatic stress disorder (PTSD) and growth hormone secretagogue receptor (GHSR) were reported to be associated with plasma lipid and glucose levels. However, interplays of PTSD with GHSR on plasma lipid and glucose levels have not been explored yet. This study was to investigate the interplays of PTSD and GHSR rs495225 on plasma glucose and lipid profiles. A total of 709 high school students were recruited at 6 months after the 2008 Wenchuan earthquake. Variants of GHSR rs495225 were identified by polymerase chain reaction-restriction fragment length polymorphism analyses and verified by DNA sequencing. The PTSD Checklist Civilian Version (PCL-C) was used to assess PTSD. There was no significant difference of PTSD prevalence between the TT homozygotes and the C allele carriers. However, the students with PTSD had significantly lower levels of glucose, insulin and homeostasis model assessment of insulin resistance (HOMA-IR) than the students without PTSD in the C allele carriers of GHSR rs495225 after the adjustment for age, gender and body mass index (BMI), but higher levels of TG and TG/HDL-C in the TT homozygotes. Meanwhile, the TT homozygotes had lower levels of HDL-C than the C allele carriers in the students without PTSD, but higher levels of insulin and HOMA-IR in the subjects with PTSD. After the adjustment of age and gender, and additional adjustment for BMI, the results were not changed except the difference of insulin was only a tendency (p = 0.054) after the additional adjustment for BMI. PTSD may augment TG levels and the related lipid ratio TG/HDL-C in the TT homozygotes of GHSR rs495225 but decrease the levels of glucose, insulin and HOMA-IR in the C allele carriers.

Reduced Recovery of Depression in Female T Allele Carriers of TNF-RII rs1061622 at Earlier Stage after Wenchuan Earthquake.

OBJECTIVE: The aim of current study was to explore longitudinally the prevalence, severity, potential factors, and predictors of depression among Chinese Han adolescent survivors with different genotypes of tumor necrosis factor receptor-II (TNF-RII) rs1061622 after the 2008 Wenchuan earthquake. METHOD: TNF-RII rs1061622 variants were examined by polymerase chain reaction⁻restriction fragment length polymorphism and verified by DNA sequencing. Depression symptoms were assessed by Beck Depression Inventory (BDI) among 439 high school students at 6, 12, and 18 months after the earthquake. RESULTS: No significant differences were observed in depression prevalence and BDI scores between the TT homozygotes and the G allele carriers in both the male and female subjects. However, the female TT homozygotes had a higher depression prevalence than the male TT homozygotes at 6, 12, and 18 months, whereas the female G allele carriers had a higher depression prevalence than the male G allele carriers only at 6 and 12 months after the earthquake. Moreover, BDI scores declined in the male subjects with both genotypes and only in the female G allele carriers at 12 months when compared with those at 6 months. Furthermore, the predictors of depression severity or potential factors of depression prevalence were different between the G allele carriers and the TT homozygotes at different times after the earthquake. CONCLUSION: It is concluded that the association of TNF-RII rs1061622 with depression is longitudinally different in Chinese Han adolescents after the 2008 Wenchuan earthquake. The T allele may be associated with reduced recovery of depression in female adolescents in the earlier stage of depression rehabilitation.

Tumor-originated exosomal lncUEGC1 as a circulating biomarker for early-stage gastric cancer.

Conventional tumor markers for non-invasive diagnosis of gastric cancer (GC) exhibit insufficient sensitivity and specificity to facilitate detection of early gastric cancer (EGC). We aimed to identify EGC-specific exosomal lncRNA biomarkers that are highly sensitive and stable for the non-invasive diagnosis of EGC. Hence, in the present study, exosomes from the plasma of five healthy individuals and ten stage I GC patients and from culture media of four human primary stomach epithelial cells and four gastric cancer cells (GCCs) were isolated. Exosomal RNA profiling was performed using RNA sequencing to identify EGC-specific exosomal lncRNAs. A total of 79 and 285 exosomal RNAs were expressed at significantly higher levels in stage I GC patients and GCCs, respectively, than that in normal controls. Through combinational analysis of the RNA sequencing results, we found two EGC-specific exosomal lncRNAs, lncUEGC1 and lncUEGC2, which were further confirmed to be remarkably up-regulated in exosomes derived from EGC patients and GCCs. Furthermore, stability testing demonstrates that almost all the plasma lncUEGC1 was encapsulated within exosomes and thus protected from RNase degradation. The diagnostic accuracy of exosomal lncUEGC1 was evaluated, and lncUEGC1 exhibited AUC values of 0.8760 and 0.8406 in discriminating EGC patients from healthy individuals and those with premalignant chronic atrophic gastritis, respectively, which was higher than the diagnostic accuracy of carcinoembryonic antigen. Consequently, exosomal lncUEGC1 may be promising in the development of highly sensitive, stable, and non-invasive biomarkers for EGC diagnosis.

Rapid screening for Klinefelter syndrome with a simple high-resolution melting assay: a multicenter study.

Klinefelter syndrome (KS) is the set of symptoms that result from the presence of an extra X chromosome in males. Postnatal population-based KS screening will enable timely diagnosis of this common chromosomal disease, providing the opportunity for early intervention and therapy at the time point when they are most effective and may prevent later symptoms or complications. Therefore, through this study, we introduced a simple high-resolution melting (HRM) assay for KS screening and evaluated its clinical sensitivity and specificity in three medical centers using 1373 clinical blood samples. The HRM assay utilized a single primer pair to simultaneously amplify specific regions in zinc finger protein, X-linked (ZFX) and zinc finger protein, Y-linked (ZFY). In cases of KS, the ratios of ZFX/ZFY are altered compared to those in normal males. As a result, the specific melting profiles differ and can be differentiated during data analysis. This HRM assay displayed high analytical specificity over a wide range of template DNA amounts (5 ng-50 ng) and reproducibility, high resolution for detecting KS mosaicism, and high clinical sensitivity (100%) and specificity (98.1%). Moreover, the HRM assay was rapid (2 h per run), inexpensive (0.2 USD per sample), easy to perform and automatic, and compatible with both whole blood samples and dried blood spots. Therefore, this HRM assay is an ideal postnatal population-based KS screening tool that can be used for different age groups.

Longitudinal interplays of estrogen receptor alpha gene rs9340799 with social-environmental factors on post-traumatic stress disorder in Chinese Han adolescents after Wenchuan earthquake.

Indirect evidences suggested associations of estrogen receptor alpha (ESR1) with post-traumatic stress disorder (PTSD). However, the relationship between rs9340799 on ESR1 gene and PTSD has not been reported yet. The present study was to explore the longitudinal changes of prevalence and severity of PTSD in adolescents with different genotypes of rs9340799 after the 2008 Wenchuan earthquake. Social-environmental factors were collected by questionnaires in 465 high school students. Variants of rs9340799 were determined by polymerase chain reaction-restriction fragment length polymorphism analyses and verified by DNA sequencing. PTSD symptoms were assessed by PTSD Checklist-Civilian Version (PCL-C) at 6, 12, and 18 months after the earthquake. The female AA homozygotes had a trend of higher prevalence of PTSD and significantly higher PCL-C scores than the female G allele carriers at 6 months after the earthquake. The female students had higher prevalence of PTSD and higher PCL-C scores than the male subjects at 6 months in the AA homozygotes, but not in the G allele carriers. Consecutive decreases in PCL-C scores were observed only in the female AA homozygotes. Only in the female, the AA genotype was the risk factor and predictor of PCL-C scores at 6 months. Potential factors of PTSD prevalence and predictors of PCL-C scores were different between the AA homozygotes and G allele carriers at different time during the follow-up. These results suggest gene-environment interactions may occur among rs9340799 and social-environmental factors, and influence the development and natural rehabilitation of PTSD in the course after stressed by the earthquake.

[Multiplex ligation-dependent probe amplification for detecting AZF microdeletions on the Y chromosome in infertile men with azoospermia or severe oligozoospermia].

OBJECTIVE: To investigate the possibility of applying multiplex ligation-dependent probe amplification (MLPA) to the detection of azoospermia factor (AZF) microdeletion on the Y chromosome in infertile men with azoospermia or severe oligozoospermia. METHODS: DNA samples were obtained from 147 azoospermia or severe oligozoospermia patients and 154 normal controls. After denatured at 95 degrees C, the samples were hybridized to the specific probes designed for the AZF region. With the ligase, the hybrid products were amplified by a pair of universal primers labeled with FAM fluorescence, and then separated by capillary electrophoresis for data analysis. Meanwhile all the samples were subjected to multiplex-PCR (mPCR) analysis for sequence-tagged sites (STS) in the AZF region. RESULTS: STS deletion was detected in 22 (15.0%) of the 147 patients but not in the normal controls. By MLPA, 40 (27.2%) of the patients were found with specific probe omission in the AZF region, as compared with 20 cases in the control group. CONCLUSION: Compared with mPCR, MLPA has a better sensitivity in detecting AZF microdeletions, and it provides more precise genetic information on the AZF regions, which may contribute to in-depth exploration into the etiological mechanism of impaired spermatogenesis.

[Noninvasive prenatal diagnosis of single gene disorders through cell-free fetal DNA in maternal blood].

The discovery of cell-free fetal DNA (cff-DNA) in maternal plasma offered a new way to noninvasive prenatal diagnosis for single gene disorders. In the past decade, many techniques such as real-time PCR, pyrophosphorolysis-activated polymerization, mass spectrum and digital PCR have been developed for noninvasive prenatal diagnosis. In this review, the author discuss the principles, applications, advantages and disadvantages of these techniques.