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.

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.

Class IIa HDAC Downregulation Contributes to Surgery-Induced Cognitive Impairment Through HMGB1-Mediated Inflammatory Response in the Hippocampi of Aged Mice.

OBJECTIVE: Perioperative neurocognitive disorders (PND) are a common complication in the elderly. Histone deacetylases (HDACs) are a class of enzymes that control the acetylation status of intracellular proteins. Thus, we explored whether HDACs trigger the release of high mobility group box 1 (HMGB1) through altering the acetylation status in the hippocampi of aged mice. MATERIALS AND METHODS: The effect of the Class IIa HDAC in PND was explored using an in vivo form of splenectomy. Sixteen-month-old healthy male C57BL/6J mice were randomly divided into five groups: control, anesthesia plus sham surgery, anesthesia plus splenectomy, LMK235 treatment, and PBS treatment. The hippocampi were harvested on either first, third, or seventh postoperative day. Cognitive function was assessed via a Morris water maze (MWM) test. Quantitative RT-PCR, Western blots and ELISAs were carried out to assess the targeted gene expression at transcriptional and translational levels. RESULTS: Splenectomy led to a significant deficiency in spatial memory acquisition, marked decreases in mRNA and protein levels of HDAC4 and HDAC5 in the hippocampus, and increases in the levels of total HMGB1 and acetylated HMGB1. In a similar fashion to splenectomy, treatment with the HDAC4/5 inhibitor LMK235 produced impaired spatial memory and an increase in the expression of HMGB1 and its acetylated counterpart in the hippocampus. CONCLUSION: These results suggest that surgery leads to PND through class IIa HDAC downregulation-triggered HMGB1 release in hippocampus of aged mice. HDACs may be a potential therapeutic target for postoperative cognitive dysfunction.

Surgery-induced downregulation of hippocampal sirtuin-1 contributes to cognitive dysfunction by inhibiting autophagy and activating apoptosis in aged mice.

OBJECTIVES: Elderly patients often suffer from cognitive dysfunction following surgery. However, the mechanisms underlying this phenomenon still remain unclear. This study investigated the critical part of Sirtuin-1 (SIRT1)-mediated autophagy and apoptosis in surgery-induced cognitive impairment. METHODS: The aged (16-month-old) male C57BL/6 mice underwent anesthesia and surgery. Some mice received intraperitoneal injections of resveratrol, which is an activator of SIRT1, prior to exposure to splenectomy. To examine learning and memory behavior in different sets, the study performed a Morris water maze. Tissues from the hippocampus were harvested 1, 3 and 7 days after surgery. Western blotting and immunofluorescence analysis determined the expression of autophagy- and apoptosis- associated protein. RESULTS: This article demonstrated surgery but not anesthesia considerably affected memory behavior and downregulated SIRT1 expression in the aged mice. Interestingly, rescue of hippocampal SIRT1 expression ameliorated the cognitive impairment in the elderly mice under splenectomy. In addition, surgical trauma decreased Beclin-1 protein levels and the LC3-II/LC3-I ratio, while expression of p62, Bax and cleaved caspase-3 in hippocampal neurons increased. However, rescue of hippocampal SIRT1 expression considerably attenuated the surgery-induced downregulation of Beclin-1, increased the ratio of LC3-II/LC3-I, and decreased expression of p62, Bax, and cleaved caspase-3. CONCLUSION: These findings suggest that surgery-induced downregulation of hippocampal SIRT1 participates in cognitive impairment after surgery by inhibiting the autophagy process and activating apoptosis.