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Association of Single Nucleotide Polymorphisms of PGC-1α Gene with Type 2 Diabetes Mellitus

Author: GuoYuPing
Tutor: PengHuiMin
School: Chongqing Medical University
Course: Genetics
Keywords: Diabetes Single nucleotide polymorphisms Insulin Resistance Peroxisome proliferator-activated receptor γ co - activator 1α
CLC: R587.1
Type: Master's thesis
Year: 2007
Downloads: 255
Quote: 2
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Abstract


Type 2 diabetes mellitus (T2DM) is a complex genetic disease heterogeneity caused by a variety of factors. Its new standards emphasize that type 2 diabetes is insulin resistance mainly associated with inadequate secretion of insulin or inadequate insulin secretion mainly associated with insulin resistance situation, in which insulin resistance causes the decrease in peripheral tissue glucose utilization and islet β-cell dysfunction The main pathological basis. In this paper, a related gene polymorphisms of insulin action, aimed at a clear correlation with diabetes. Human PGC-1α gene is located on chromosome 4p15.1, full-length 67kb, contains 13 exons encoding a 798 amino acid protein with a molecular weight of 91kD. PGC-1α was first to be discovered as a PPARγ coactivator, is a multi-functional transcription regulatory factors, widely different signal transduction pathways involved in the regulation of energy metabolism in many other aspects, such as adaptive thermogenesis liver gluconeogenesis, fatty acid β oxidation, muscle glucose transporter, mitochondrial biosynthesis process. Recent studies have shown, PGC-1α involved in the formation of insulin resistance (IR), research that PGC-1α can accelerate the the liver gluconeogenesis process, induced intrahepatic IR; while by affecting islet β-cell glucose-stimulated insulin secretion (CSIS ) caused by pancreatic β cell IR; contrary, increased expression of PGC-1α can reduce the proportion of skeletal muscle fat, increase the aerobic muscle type, and insulin sensitivity, and thus relieve skeletal muscle IR. Considerable evidence that PGC-1α is closely linked to the metabolic syndrome of insulin resistance based. Studies of different ethnic groups found the chromosomal region containing the PGC-1α gene and metabolic syndrome related characterization linkage; and PGC-1α gene mutations have varying degrees of contact with the metabolic syndrome in different ethnic groups in multinational reported; gene polymorphism variation may have an impact on insulin secretion. Therefore, PGC-1α as a candidate gene for type 2 diabetes, the study will help proved the pathogenesis of diabetes molecule drug therapy for metabolic diseases to provide new ideas. The purpose of this study is to understand China's southwestern region the Han population PGC-1α gene SNPs and haplotype frequency distribution, to explore the relationship between the haplotype SNPs and its two sites with type 2 diabetes, the accumulation of PGC-1α gene SNPs in China Han population data, is conducive to the study of T2DM pathogenesis. Objective To study the allele frequency of southwest China Han PGC-1α SNPs in two genes, genotype frequencies and its components haplotype distribution characteristics. Correlation of PGC-1α gene SNPs and haplotype frequencies with T2DM. PGC-1α gene sequences and their corresponding sites of research methods (1) through (USA), the National Center for Biotechnology Information (NCBI) GenBank Get the SNP the information. The corresponding primers using Primer Premier 5.0 primer design software design, and test its specificity via the NCBI Blast2.0 software. (2) the application of PCR-RFLP technique detected T2DM patient group and the control group PGC-1α gene 2 SNPs locus genotype. (3) application of cluster analysis method to analyze the characteristics of genetic polymorphisms. Findings (1) PCR-RFLP method for detection of SNPs with simple, good reproducibility, and the results are stable. (2) the frequency of allele the frequency: PGC-1α gene 2 SNPs rs8192678 (Gly482Ser G → A), rs3736265 (Thr612Met C → T) dominant allele (Allele 1) in the case and control groups, respectively: 0.533 / 0.647 (P lt; 0.05) 0.745/0.799 (P gt; 0.05); frequency of the non-dominant allele (Allele 2) in the case group and the control group were: 0.467/0.353 (P lt; 0.05), 0.255 / 0.201 (P gt; 0.05) (3) genotype frequencies: PGC-1α gene SNPs rs8192678, rs3736265 two points SNP allele frequency in the case group and the control group were: rs8192678 G / G type for 0.321/0.412 , G / A type 0.425/0.471 A / A type 0.255/0.118 two sets of allele frequency distribution of significant difference (P lt; 0.05). rs3736265 C / C type 0.585/0.657, C / T type 0.321/0.284 T / T-type 0.094/0.059, two sets of allele frequency distribution was no significant difference (P> 0.05). (4) haplotype frequencies: two SNPs, can be composed of four haplotypes, the Han population in southwest China, the most common type of GC, AC, the frequency of the patient and control groups, respectively 0.460/0.515 0.278/0.285 (P gt; 0.05); the AT haplotype frequency in the patient and control groups, respectively for 0.185/0.077 (P lt; 0.05), its distribution has significant differences. Conclusion (1) PCR-RFLP technique is a simple, mature and stable, reproducible, high specificity, the results are reliable SNP detection method. (2) The study revealed two SNPs sites in southwest China Han population PGC-1α genotype and haplotype distribution relationship with diabetes, for further study of the relationship of SNPs genotype with physiological cases mechanisms and diseases provide a theoretical reference. (3) PGC-1α gene SNPs rs8192678 locus may be associated with southwest China Han population T2DM.

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CLC: > Medicine, health > Internal Medicine > Endocrine diseases and metabolic diseases > Islet disease > Diabetes
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