| ObjectiveTo investigate the PTPN22 single nucleotide polymorphism and its relationship with the pathogenesis of type 1 diabetes mellitus.Subject and Methods364 type 1 diabetes mellitus patients and 728 normal children were recruited. Genomic DNA was extracted from their peripheral blood leukocytes, genotypes of rs2488457, rs3765598, rs1217419, rs1217414, rs2476601 of PTPN22 gene were determined using SNaPshot method. Gene frequencies and allele frequencies between T1D patients and normal controls were compared, and their relations with clinical traits were analysized. All the data were analysed by SPSS 17.0 software.Result1. The frequencies of GG, GC, CC genetypes of rs2488457 in T1D group were 9.0%, 47.8%,42.3% respectively; The frequencies of GG, GC, CC genetypes in normal control group were 12.4%,39.4%,48.2% respectively. Genotype frequencies of rs2488457 differed significantly between TID and normal control group(x2=7.084,p=0.029). The prevalence of the GC genotype was higher in the patients than that in normal controls. There was no significant association between rs2488457 and the patients'clinical measurements including geneder, age of onset, season of onset, HbAlc, serrum C petide, DKA, AITD, IAA, ICA, GAD65-Ab and IA2-Ab levels.2. The frequencies of the rs3765598 genotypes were no significantly difference in TID group and normal control group(x2=3.296, p=0.192). There was no significant association between rs3765598 and the patients'clinical measurements including geneder, age of onset, season of onset, HbAlc, serrum C petide, DKA, AITD, IAA, ICA, GAD65-Ab and IA2-Ab levels. 3. The frequencies of CC, CA, AA genetypes of rs 1217419 in T1D group was 2.5%, 25.4%,72.1%;The frequence of CC, CA, AA genetypes in normal control group were 0.8%,20.5%,78.7%. Genotype frequencies of rs2488457 differed significantly between T1D and normal control group(x2=8.910,p=0.012).The frequencies of C allele in T1D group were higher in the patients than that in normal controls (x2=7.598,p=0.006). The frequencies of C, A allele in male patients were 12.3%,87.7%, which in female patients were18.2%,81.8%. The allele frequencies differed significantly between male and female patients(x2=4.825,p=0.028).4. The frequencies of the rs1217414 genotypes were no significantly difference in T1D and normal control groups (x2=2.866, p=0.208). The frequencies of C, T allele in male patients were 97.3%,2.7%, which in female patients were 92.5%,7.5%. The allele frequencies differed significantly between male and female patients(x2=8.534,p=0.003).5. The genetypes of rs2476601 in T1D and normal control groups are all CC genetype.ConclusionThe PTPN22 gene single nucleotide polymorphisms were significantly correlated with the pathogenesis of T1D, rs1217419 polymorphism was firstly proved be related with T1D pathogenesis. The homogeneous CC genotype rs2476601, a proved T1D susceptible SNP in Caucasians, conincide with same found in other Asia population demonstrated the unique ethic functional difference of PTPN22 gene in the pathogenesis of type 1 diabetes. ObjectiveTo investigate the CTLA-4 single nucleotide polymorphism and its relationship with the pathogenesis of type 1 diabetes mellitus.Subject and Methods364 type 1 diabetes mellitus patients and 728 normal children were recruited. Genomic DNA was extracted from their peripheral blood leukocytes, genetypes of rs231775, rs3087243, rs5742909 in CTLA-4 gene were determined using SNaPshot method. Gene frequencies and allele frequencies between T1D patients and normal controls were compared, and their relations with clinical traits were analysized. All the data were analysed by SPSS 17.0 software.Result1. The frequencies of G, A allele of rs231775 in T1D group were 74.2%,25.8% respectively; The frequencies of G, A allele in normal control group were 67.1%, 32.9%.Allele frequencies of rs231775 differed significantly between T1D group and normal group(x2=11.332,p=0.001). HbAlc level of patients with the AA genotype was higher than that in patients with GA and GG genotypes(x2=1,p=0.039). The frequencies of G allele differed significantly between GAD65 antibody positive patients and controls (x2=6.787,p=0.009).2. The frequencies G, A allele of rs3087243 in T1D group were 86.1%,13.9%; The frequencies G, A allele in normal control group were 80.5%,19.5%. Allele frequencies differed significantly between T1D group and normal group(x2=10.458, p=0.001). There was no significant association between rs3087243 and the patients' clinical measurements including geneder, age of onset, season of onset, HbA1c, serrum C petide, DKA, AITD, IAA, ICA, GAD65-Ab and IA2-Ab levels. 3. The frequencies of the rs5742909 genotypes were no significantly difference in T1D group and normal control groups(x2=1.075,p=0.584). HbAlc level of patients with the TT genotype was higher than that in patients with CT and CC genotypes (f=3.514, p=0.032). The frequencies of C allele differed significantly between GAD65 antibodies positive patients and GAD65 antibodies negative patients (p=0.002, x2=9.208).ConclusionThe CTLA-4 gene single nucleotide polymorphisms were significantly correlated with type 1 diabetes pathogenesis, which are compatible with other studies in different population, the universal correlation of CTLA-4 gene with T1D demonstrated that it may play essential role in the pathogenesis on T1D. ObjectiveTo identify the gene mutation in neonatal diabetes mellitus, to compare the effect of insulin and sulfonylurea.Subject and MethodsFourteen neonatal diabetes mellitus (NDM) patients were recruited, KCNJ11, ABCC8, INS genes were sequenced for mutation analysis,9 patients were treated with sulfonylurea and the other 5 patients were treated with insulin.ResultTwo patients were found with ABCC8 gene mutation, one with KCNJ11 gene mutation, one with INS gene muation, one with 6q24 hypomethylation, one without analysised genes muation.88.9%(8/9) patients reached euglycemia with sulfonylurea except one INS mutation patients. Other five patients with insulin therapy were lose of contact.Conclusion1. Although the mutation spectrum is diverse, high frequency of KCNJ11, ABCC8 were found in the subjects.2. Sulfonylurea therapy was well tolerant without evident side-effects and euglycemia were reached in most of the patients. |
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