目的探讨2型糖尿病(T2DM)患者SLC2A2 rs5393、rs5400位点基因多态性与二甲双胍疗效的相关性。方法选取2016年1月至2019年4月期间在山西医科大学第一医院就诊的T2DM患者90例(T2DM组)及90例体检健康者(对照组)作为研究对象,通过PCR-限制...目的探讨2型糖尿病(T2DM)患者SLC2A2 rs5393、rs5400位点基因多态性与二甲双胍疗效的相关性。方法选取2016年1月至2019年4月期间在山西医科大学第一医院就诊的T2DM患者90例(T2DM组)及90例体检健康者(对照组)作为研究对象,通过PCR-限制性片段长度多态性(PCR-RELP)法检测SLC2A2 rs5393、rs5400位点基因多态性分布频率。对T2DM患者进行二甲双胍治疗,随访90 d,分析二甲双胍疗效与各基因型的关系。结果对照组与T2DM组SLC2A2 rs5393、rs5400各基因型符合Hardy-Weinberg平衡定律。与对照组相比,T2DM组rs5393位点AC型、CC型比例显著升高(P<0.05),rs5400位点CT、TT型频率显著升高(P<0.05)。rs5393位点中,治疗前AA型、AC型、CC型空腹血糖(FBG)、餐后2 h血糖(2 h PBG)、糖化血红蛋白(HbA1c)水平差异无统计学意义(P>0.05);二甲双胍治疗后AC型、CC型患者FPG、2 h PBG、HbA1c降低幅度低于AA型(P<0.05),CC型FPG、HbA1c降低幅度低于AC型(P<0.05)。rs5400位点中,治疗前CC型、CT型、TT型FPG、2 h PBG、HbA1c水平差异无统计学意义(P>0.05);二甲双胍治疗后CT型、TT型患者FPG、2 h PBG、HbA1c降低幅度低于CC型(P<0.05),TT型FPG、HbA1c降低幅度低于CT型(P<0.05)。结论SLC2A2基因多态性位点rs5393 AA型患者、rs5400 CC型T2DM患者对二甲双胍敏感,降糖疗效较好。展开更多
Human endogenous retroviruses(HERVs)are remnants of retroviral infections in human germline cells from millions of years ago.Among these,ERVW-1(also known as HERV-W-ENV,ERVWE1,or ENVW)encodes the envelope protein of t...Human endogenous retroviruses(HERVs)are remnants of retroviral infections in human germline cells from millions of years ago.Among these,ERVW-1(also known as HERV-W-ENV,ERVWE1,or ENVW)encodes the envelope protein of the HERV-W family,which contributes to the pathophysiology of schizophrenia.Additionally,neuropathological studies have revealed cell death and disruption of iron homeostasis in the brains of individuals with schizophrenia.Here,our bioinformatics analysis showed that differentially expressed genes in the human prefrontal cortex RNA microarray dataset(GSE53987)were mainly related to ferroptosis and its associated pathways.Clinical data demonstrated significantly lower expression levels of ferroptosis-related genes,particularly Glutathione peroxidase 4(GPX4)and solute carrier family 3 member 2(SLC3A2),in schizophrenia patients compared to normal controls.Further in-depth analyses revealed a significant negative correlation between ERVW-1 expression and the levels of GPX4/SLC3A2 in schizophrenia.Studies indicated that ERVW-1 increased iron levels,malondialdehyde(MDA),and transferrin receptor protein 1(TFR1)expression while decreasing glutathione(GSH)levels and triggering the loss of mitochondrial membrane potential,suggesting that ERVW-1 can induce ferroptosis.Ongoing research has shown that ERVW-1 reduced the expression of GPX4 and SLC3A2 by inhibiting their promoter activities.Moreover,Ferrostatin-1(Fer-1),the ferroptosis inhibitor,reversed the iron accumulation and mitochondrial membrane potential loss,as well as restored the expressions of ferroptosis markers GSH,MDA,and TFR1 induced by ERVW-1.In conclusion,ERVW-1 could promote ferroptosis by downregulating the expression of GPX4 and SLC3A2,revealing a novel mechanism by which ERVW-1 contributes to neuronal cell death in schizophrenia.展开更多
Importance:Transient neonatal zinc deficiency(TNZD)occurs in breastfed infants due to abnormally low breast milk zinc levels.Mutations in the solute carrier family 30 member 2(SLC30A2)gene,which encodes the zinc trans...Importance:Transient neonatal zinc deficiency(TNZD)occurs in breastfed infants due to abnormally low breast milk zinc levels.Mutations in the solute carrier family 30 member 2(SLC30A2)gene,which encodes the zinc transporter ZNT2,cause low zinc concentration in breast milk.Objective:This study aimed to provide further insights into TNZD pathophysiology.Methods:SLC30A2 sequencing was performed in three unrelated Japanese mothers,whose infants developed TNZD due to low-zinc milk consumption.The effects of the identified mutations were examined using cell-based assays and luciferase reporter analysis.Results:Novel SLC30A2 mutations were identified in each mother.One harbored a heterozygous missense mutation in the ZNT2 zinc-binding site,which resulted in defective zinc transport.The other two mothers exhibited multiple heterozygous mutations in the SLC30A2 promoter,the first mutations in the SLC30A2 regulatory region reported to date.Interpretation:This report provides new genetic insights into TNZD pathogenesis in breastfed infants.展开更多
文摘目的探讨2型糖尿病(T2DM)患者SLC2A2 rs5393、rs5400位点基因多态性与二甲双胍疗效的相关性。方法选取2016年1月至2019年4月期间在山西医科大学第一医院就诊的T2DM患者90例(T2DM组)及90例体检健康者(对照组)作为研究对象,通过PCR-限制性片段长度多态性(PCR-RELP)法检测SLC2A2 rs5393、rs5400位点基因多态性分布频率。对T2DM患者进行二甲双胍治疗,随访90 d,分析二甲双胍疗效与各基因型的关系。结果对照组与T2DM组SLC2A2 rs5393、rs5400各基因型符合Hardy-Weinberg平衡定律。与对照组相比,T2DM组rs5393位点AC型、CC型比例显著升高(P<0.05),rs5400位点CT、TT型频率显著升高(P<0.05)。rs5393位点中,治疗前AA型、AC型、CC型空腹血糖(FBG)、餐后2 h血糖(2 h PBG)、糖化血红蛋白(HbA1c)水平差异无统计学意义(P>0.05);二甲双胍治疗后AC型、CC型患者FPG、2 h PBG、HbA1c降低幅度低于AA型(P<0.05),CC型FPG、HbA1c降低幅度低于AC型(P<0.05)。rs5400位点中,治疗前CC型、CT型、TT型FPG、2 h PBG、HbA1c水平差异无统计学意义(P>0.05);二甲双胍治疗后CT型、TT型患者FPG、2 h PBG、HbA1c降低幅度低于CC型(P<0.05),TT型FPG、HbA1c降低幅度低于CT型(P<0.05)。结论SLC2A2基因多态性位点rs5393 AA型患者、rs5400 CC型T2DM患者对二甲双胍敏感,降糖疗效较好。
基金supported by the National Natural Science Foundation of China(Nos.82272321 and 81971943)Fundamental Research Funds for the Central Universities(2042023kf0230)the Stanley Foundation from the Stanley Medical Research Institute(SMRI),United States(No.06R-1366).
文摘Human endogenous retroviruses(HERVs)are remnants of retroviral infections in human germline cells from millions of years ago.Among these,ERVW-1(also known as HERV-W-ENV,ERVWE1,or ENVW)encodes the envelope protein of the HERV-W family,which contributes to the pathophysiology of schizophrenia.Additionally,neuropathological studies have revealed cell death and disruption of iron homeostasis in the brains of individuals with schizophrenia.Here,our bioinformatics analysis showed that differentially expressed genes in the human prefrontal cortex RNA microarray dataset(GSE53987)were mainly related to ferroptosis and its associated pathways.Clinical data demonstrated significantly lower expression levels of ferroptosis-related genes,particularly Glutathione peroxidase 4(GPX4)and solute carrier family 3 member 2(SLC3A2),in schizophrenia patients compared to normal controls.Further in-depth analyses revealed a significant negative correlation between ERVW-1 expression and the levels of GPX4/SLC3A2 in schizophrenia.Studies indicated that ERVW-1 increased iron levels,malondialdehyde(MDA),and transferrin receptor protein 1(TFR1)expression while decreasing glutathione(GSH)levels and triggering the loss of mitochondrial membrane potential,suggesting that ERVW-1 can induce ferroptosis.Ongoing research has shown that ERVW-1 reduced the expression of GPX4 and SLC3A2 by inhibiting their promoter activities.Moreover,Ferrostatin-1(Fer-1),the ferroptosis inhibitor,reversed the iron accumulation and mitochondrial membrane potential loss,as well as restored the expressions of ferroptosis markers GSH,MDA,and TFR1 induced by ERVW-1.In conclusion,ERVW-1 could promote ferroptosis by downregulating the expression of GPX4 and SLC3A2,revealing a novel mechanism by which ERVW-1 contributes to neuronal cell death in schizophrenia.
基金supported by a Grant-in-Aid for Scientific Research on Innovative Areas"Integrated Bio-metal Science"(MEXT KAKENHI Grant Number JP19H05768)from the Ministry of Education,Culture,Sports,Science,and Technologya Grant-in-Aid for Scientific Research(B)(JSPS KAKENHI Grant No.JP19H02883)from the Japan Society for the Promotion of Science(to Taiho Kambe).
文摘Importance:Transient neonatal zinc deficiency(TNZD)occurs in breastfed infants due to abnormally low breast milk zinc levels.Mutations in the solute carrier family 30 member 2(SLC30A2)gene,which encodes the zinc transporter ZNT2,cause low zinc concentration in breast milk.Objective:This study aimed to provide further insights into TNZD pathophysiology.Methods:SLC30A2 sequencing was performed in three unrelated Japanese mothers,whose infants developed TNZD due to low-zinc milk consumption.The effects of the identified mutations were examined using cell-based assays and luciferase reporter analysis.Results:Novel SLC30A2 mutations were identified in each mother.One harbored a heterozygous missense mutation in the ZNT2 zinc-binding site,which resulted in defective zinc transport.The other two mothers exhibited multiple heterozygous mutations in the SLC30A2 promoter,the first mutations in the SLC30A2 regulatory region reported to date.Interpretation:This report provides new genetic insights into TNZD pathogenesis in breastfed infants.
