| Background: Type 2 diabetes mellitus is a complicated heterogeneous disease. It is known that B cell dysfunction and impaired insulin-stimulated glycogen synthesis of the peripheral tissue are the most consistent pathophogenesis characteristics of type 2 diabetes. To explore the relationship between Protein Tyrosine Phosphatase non-receptor type 1 (PTPN1)gene and type 2 diabetes, we studied polymorphisms of PTPN1 gene which encode Protein-tyrosine Phosphatase-1B (PTP1B).The human PTPN1 gene maps at 20ql3.1-q13.2. PTP1B encoded by the PTPN1 gene, catalyzes the dephosphorylation of tyrosine residues of the insulin receptor kinase activation segment and IRS1 resulting in the down-regulation of insulin signalling. The disruption of the PTPN1 gene in mice resulted in increased insulin sensitivity and resistance to diet-induced obesity. As PTPN1 gene might be associated with T2DM, we studied it as a candidate gene for T2DM.The study aimed to investigate the relationship between the allelic and haplotype frequency distribution of three SNPs in PTPN1 gene and T2DM in southern Chinese Han population and provide PTPN1 gene SNPs information in southern Chinese Han population which would facilitate further exploration into the etiopathogenesis, precaution and treatment of T2DM.Objectives(1)To study the genotype frequency, the allelic frequency and the haplotype frequency distribution of three SNPs including SNP rs2904268, rs2230605 and rs16995309 in PTPN1 gene.(2)To study the relationship between PTPN1 gene three SNPs and T2DM.Methods(1)We collected the information about PTPN1 gene nucleotide sequences and three SNPs from GenBank of National Center for Biotechnology Information (NCBI).The primers were designed by Primer Premier 5.0 software and their specificities were tested by NCBI Blast 2.0 software.(2)The genotypes of three SNPs rs2904268, rs2230605 and rs16995309 were determined by Bi-PASA PCR technique.(3)The genotypes combination distribution of three SNPs of PTPN1 gene was analyzed by clustering analysis technique. There was considered significant difference when p value was 0.05 or less statistically. Results(1) We successfully studied three SNPs in PTPN1 gene by using Bi-PASA PCR technique. The superiority and stability of Bi-PASA PCR technique on determining gene SNPs had been tested.(2) The allele 1 frequencies of SNPs rs2904268, rs2230605and rs16995309 in T2DM cases were 0.611, 0.648 and 0.708 respectively while in control subjects were 0.686, 0.642, 0.691 respectively.There were no significant differences between every two groups(All p valuesï¹¥0.05).(3) G/G, G/C and C/C genotypes frequencies of SNP rs2904268 in T2DM cases and control subjects were 0.361/0.480, 0.500/0.412, 0.139/0.108 respectively. A/A, A/G and G/G genotypes frequencies of SNP rs2230605 in T2DM cases and control subjects were 0.380/0.382, 0.537/0.520 and 0.083/0.098 respectively. Genotypes frequencies of SNP rs16995309 in T2DM cases and control subjects were C/C 0.481/0.549,C/T 0.454/0.402 and T/T 0.065/0.049 respectively. There were no significant differences between the two groups in three SNPs(All p valuesï¹¥0.05).(4) The most three common haplotypes of PTPN1 gene among Chinese Han population were C A C, G A C and G G C*, frequencies of which in both groups were 0.145/0.168,0.346/0.276 and 0.112/0.229 respectively. P values were 0.522383, 0.117102 and 0.001465 respectively. The haplotype frequencies of G A T* and G G T* were 0.069/0.155, 0.083/0.027 respectively.p values were 0.005001 and 0.011742 respectively. There were significant differences between T2DM cases and control subjects. Conclusively PTPN1 gene polymorphisms might be associated with T2DM.Conclusions(1) The Bi-PASA PCR technique is a novel method by which we can conveniently determine SNP with more specificity, less expenditure, especially in detecting the zygosity of known mutations.(2) We found the features of genotypes combination distribution and frequencies distribution of three SNPs of PTPN1 gene and provided basic laboratory biological information which would facilitate further exploration into the etiopathogenesis, precaution and treatment of T2DM.(3) We found PTPN1 gene haplotypes might be associated with T2DM in southern Chinese Han population. |
PDF Full Text Request