Isoform-and cell-state-specific APOE homeostasis and function

Apolipoprotein E is the major lipid transporter in the brain and an important player in neuron-astrocyte metabolic coupling.It ensures the survival of neurons under stressful conditions and hyperactivity by nourishing and detoxifying them.Apolipoprotein E polymorphism,combined with environmental stresses and/or age-related alterations,influences the risk of developing late-onset Alzheimer’s disease.In this review,we discuss our current knowledge of how apolipoprotein E homeostasis,i.e.its synthesis,secretion,degradation,and lipidation,is affected in Alzheimer’s disease.

Effects of Impaired Glucose Metabolism on Heart Rate Variability and Blood Pessure Variability in Essential Hpertensive Patients

To investigate the effects of impaired glucose metabolism （IGM） on cardiovascular autonomic nervous systems in essential hypertensive （EH） patients by comparing heart rate variability （HRV） and blood pressure variability （BPV） in EH patients with or without type 2 diabetes mellitus （T2DM）. Simultaneous 24-h recordings of ambulatory ECG and blood pressure monitoring were performed in 36 male old patients with simple EH and 33 male old patients with EH combined with T2DM. HRV analysis included time domain parameters such as SDNN, SDANN, SDNNi, rMSSD and pNN50, and total spectral power （TP） of HRV, which mainly consists of VLF, LF and HF component along with LF/HF ratio, was also obtained. The value of ambulatory blood pressure was represented as the mean blood pressure （mean systolic/mSBP, diastolic/mDBP and pulse pressure/mPP） during different periods （24 h/24 h, day time/d and night time/n）. Standard deviation （SD） as well as coefficient of variance （CV） of blood pressure during each above-mentioned period were obtained to reflect the long-term BPV. Our result showed that SDNN, SDNNi, SDANN, rMSSD, PNN50, TP and HF of HRV in cases of EH with T2DM were all significantly lower than those in simple EH subjects （P〈0.05）. No significant differences in VLF or LF was found between the two groups （P〉0.05）, while LF/HF ratio was significantly higher in EH with T2DM patients than in simple EH subjects （P〈0.01）. Moreover, dmSBP, 24 h-mPP and dmPP were all significantly higher in EH with T2DM patients than in simple EH subjects （P〈0.05）, while nmSBP, 24 h-mSBP, 24 h-mDBP, dmDBP, nmDBP or nmPP showed no significant difference between this two groups of patients （P〉0.05）. And dSBPSD, dSBPCV and 24 h-SBPSD were all significantly higher in EH with T2DM patients than in simple EH subjects （P〈0.05）, while the other BPV indexes showed no significant difference between this two groups （P〉0.05）. It is concluded that the cardiovascular autonomic nervous systems in EH patients was further impaired by T2DM, displaying lowering of HRV and enlargement of BPV, which in turn induced abnormal structural and functional changes of cardiovascular systems. Therefore, improving cardiovascular autonomic nervous systems might reduce the occurrence of cardiovascular complications in the EH patients with IGM.

Heterogeneity in susceptibility to polycystic ovary syndrome among women with epilepsy

Background Epilepsy comorbidities adversely affect the quality of life of patients.Women with epilepsy are at a high risk of comorbid endocrine disorders.Among them,the polycystic ovary syndrome(PCOS)has a threefold higher prevalence in women with epilepsy than in healthy women and is the main cause of infertility among the patients.Clinically,women with epilepsy show heterogeneity in the susceptibility to PCOS.This heterogeneity may be associated with genetic factor.Methods To test this,we retrospectively collected clinical data from 45 female patients with epilepsy and divided them into three groups according to their susceptibility to PCOS.Groups A and B represented a high susceptibility to PCOS.Patients in Group A were diagnosed with PCOS before their first seizure,while patients in Group B were diagnosed with PCOS after a short period of monotherapy with a low dose of antiseizure medication(ASM)following the diagnosis of epilepsy.Patients in Group C did not develop PCOS despite a prolonged treatment with high-dose ASM.We compared the clinical data and genetic profiles among the three groups.Results We found a clear trend of impaired metabolism in Group B patients and this may be associated with highfrequency mutations in MYO10 and ADGRL3.Conclusions Our study suggests that women with epilepsy are heterogeneous in the susceptibility to PCOS and this is associated with mutations in specific genes.Therefore,genetic screening should be conducted to screen for women with epilepsy who are more likely to have comorbid PCOS,so that they can receive targeted interventions at an early stage to reduce the risk.

Positive Association Between Type 2 Diabetes Risk Alleles Near CDKAL1 and Reduced Birthweight in Chinese Han Individuals

Background： Fetal insulin hypothesis was proposed that the association between low birth weight and type 2 diabetes is principally genetically mediated. The aim of this study was to investigate whether common variants in genes CDKALI, HHEX, ADCY5, SRR, PTPRD that predisposed to type 2 diabetes were also associated with reduced birthweight in Chinese Han population.Methods： Twelve single nucleotide polymorphisms （rs7756992/rs10946398 in CDKAL1, rsl 111875 in HHEA; rs391300 in SRR, rs17584499 in PTPRD. rs1170806/rs9883204/rs4678017/rs9881942/rs7641344/rs6777397/rs6226243 in ADCY5） were genotyped in 1174 unrelated individuals born in Peking Union Medical College Hospital from 1921 to 1954 by TaqMan allelic discrimination assays, of which 645 had normal glucose tolerance, 181 had developed type 2 diabetes and 348 impaired glucose regulation. Associations of these 12 genetic variants with birthweight and glucose metabolism in later life were analyzed.Results： Birthweight was inversely associated with CDKAL 1-rs 10946398 （β = -41 g [95% confidence interval [CI]： -80, 3], P= 0.034）, common variants both associated with increased risk of impaired glucose metabolism and decreased insulin secretion index later in life. After adjusting for sex, gestational weeks, parity and maternal age, the risk allele of CDKAL1-rs7756992 was associated with reduced birthweight （β = 36 g [95% CI： -72, -0.2], P = 0.048）. The risk allele in SRR showed a trend toward a reduction ofbirthweight （P =0.085）. Conclusions： This study identified the association between type 2 diabetes risk variants in CDKAL 1 and birthweight in Chinese Hart individuals, and the carrier of risk allele within SRR had the trend of reduced birthweight. This demonstrates that there is a clear overlap between the genetics of type 2 diabetes and fetal growth, which proposes that lower birth weight and type 2 diabetes may be two phenotypes of one genotype.

Analysis of Patients With Coronary Heart Disease Combined With Impaired Glucose Metabolism

Objectives To study the morbidity of patients with coronary artery disease （CAD） combined with impaired glucose metabolism. Methods Retrospective analysis of clinical data about patients with CAD in 1997, 2002 and 2007, separately. A total of 2951 patients were enrolled, among whom had coexistence of 457 abnormal glycometabolism, including impaired fasting glucose, impaired glucose tolerance and type 2 diabetes mellitus. Results The prevalence of abnormal glycometabolism in patients with CAD was increasing year by year. The morbidity raised from 3.8% and 16.5% to 10. 8% in these three years. Conclusion It is more and more common to detect CAD with impaired glucose metabolism, and it should be emphasized in the secondary prevention of CAD.