目的分析KCNQ1及SLC30A8基因多态性与2型糖尿病(T2DM)患者的相关性。方法选取2015年9月~2017年9月间在本院确诊并接受治疗的T2DM患者100例作为观察组,选取同期在本院进行体检健康者100例作为对照组,收集两组对象早晨空腹静脉血5 m L,全...目的分析KCNQ1及SLC30A8基因多态性与2型糖尿病(T2DM)患者的相关性。方法选取2015年9月~2017年9月间在本院确诊并接受治疗的T2DM患者100例作为观察组,选取同期在本院进行体检健康者100例作为对照组,收集两组对象早晨空腹静脉血5 m L,全自动生化分析仪检测糖化血红蛋白、空腹血糖水平、胰岛素和血脂的水平,基因型检测使用单碱基延伸法,分析不同基因位点和T2DM相关性状况。结果 SLC30A8基因对照组TT、CT及CC基因型的频率依次为16%、52%及32%,观察组依次为13%、49%、38%,差异无统计学意义(χ~2=1.290,P>0.05);对照组T、C等位的基因频率依次为61%、39%,观察组依次为73%、27%,差异有统计学意义(95%CI=0.795~1.684,OR=1.205,χ~2=11.553,P<0.05)。观察组TT基因型血清FINS及HOMA-B高于CT基因型和CC基因型,观察组TT基因型血清TC、TG和FPG低于CT基因型和CC基因型,差异均有统计学意义(P<0.05);KCNQ1基因对照组TT、CT及CC基因型的频率依次为27%、41%及32%,观察组依次为24%、45%、31%,差异无统计学意义(χ~2=2.006,P>0.05);对照组T、C等位的基因频率依次为53%、47%,观察组依次为64%、36%,差异有统计学意义(95%CI=0.863-2.104,OR=1.171,χ~2=12.995,P<0.05),CC基因型血清TC、TG、FPG及Hb A1c低于CT、TT基因型,血清FINS高于CT、TT基因型,差异均有统计学意义(P<0.05)。结论 SLC30A8基因多态性rs13266634位点和KCNQ1基因多态性rs2237892位点和T2DM发病及血管并发症有一定相关性。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
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.
