| Type 2 diabetes mellitus (T2DM) is a complicated heterogeneous disease. Now in the new standands T2DM can be divided into the two main condition: one that insulin resistance is the key accompanying hypoinsulinism;the other that hypoinsulinism is the major coupled with insulin resistance. The main pathophysiology is insulin resistance in periphery tissue which would cause decreased glucose utilization, combined with decliningβ-cell function. In the present study, we aimed to identify the association of insulin related gene with T2DM by investigating genetic polymorphisms.The PGC-1αgene, full length of 67kb, located on human chromosome 4p15.1, contain 13 exons and encode a protein with a 91kD molecular weight, which comprised 798 amino acids. PGC-1α, found first a co-activator of PPARγ, is a multifunctional regulatory factor at transcriptional level through various signal transduction involved in energy metabolism regulation, including adaptive thermogenesis, hepatic gluconeogenesis,β-oxidation of fatty acids, glucose transport in muscle, mitochondrial biosynthesis, and so on. Recent evidence shows that an involvement of PGC-1αin the development of insulin resistance. In liver, PGC-1αwould be expected to accelerate hepatic gluconeogenesis, which might induce insulin resistance. In pancreaticβ-cell, increased PGC-1αexpression or function would be expected to cause insulin resistance through influencing on the glucose-stimulated insulin secretion. However, in skeletal muscles, increases in PGC-1αexpression may result in decreased fatty specific gravity ,increased formation of mitochondria-rich oxidative muscles and insulin susceptibility, which might relieve insulin resistance in muscles.More and more evidence indicate that PGC-1αis well connection with metabolism syndrome characterized by insulin resistance. Studies on various ethnic population have found that PGC-1αgene maps to the chromosome region of well linkage to related superficial metabolism syndrome. Moreover, it has been reported that PGC-1αgene mutation among the various race in many countries exists a correlation in distinct degree with metabolism syndrome. Thus, PGC-1αgene polymorphisms might affect on insulin secretion. Therefore, PGC-1αgene is regarded as a strong functional and positional candidate gene for T2DM, which will conduce to understand pathogenesis of T2DM and supply valuable clue for molecule drug therapy of metabolic diseases. In the present study, we aimed to investigate single nucleotide polymorphisms(SNPs) and haplotype frequency distribution in PGC-1αgene, and identify the association of two SNPs with T2DM among the southwest Chinese Han population, which will accumulate more data of PGC-1αpolymorphisms facilitated further studies on pathogenesis of T2DM.ObjectivesTo investigate the allele frequency distribution, the genotypic frequency and haplotype frequency distribution of the two SNPs of PGC-1αgene among southwest Chinese Han population. To study the correlation of SNPs and haplotype frequency of PGC-1αgene with T2DM.Methods(1) PGC-1αgene nucleotide sequences and the corresponding SNPs were obtained from GenBank of National Center for Biotechnology Information(NCBI).The primers were designed using Primer premier 5.0 software and their specificity were analyzed by NCBI Blast 2.0 software.(2)The two SNPs of PGC-1αgene between the T2DM cases and normal controls were genotyped with Polymerase Chain Reaction-Restriction Fragment Length Polymorphism(PCR-RFLP) technique.(3)The genotypes combination distribution of two SNPs of PGC-1α gene was analyzed by clustering analysis method.Results(1)PCR-RFLP is a technique ,which can conveniently determine SNPs with more reproducibility and stability.(2)The predominance allele1 frequency of SNPs rs8192678 (Gly482Ser G→A) and rs3736265(Thr612Met C→T) in PGC-1αgene between the T2DM cases and controls subjects were 0.533/0.647(P<0.05) and 0.745/0.799(P>0.05) respectively; Allele2 frequency of SNPs rs8192678 and rs3736265 in PGC-1αgene between the T2DM cases and controls subjects were 0.467/0.353(P<0.05) and 0.255/0.201(P>0.05) respectively.(3)The genotypes frequency of SNPs in PGC-1αgene between cases and controls, SNP rs8192678: frequency G/G 0.321/0.412, G/A 0.425/0.471, A/A 0.255/0.118(P<0.05), There were significant differences between T2DM cases and controls subjects; SNP rs3736265: frequency C/C 0.585/0.657, C/T 0.321/0.284, T/T 0.094/ 0.059(P>0.05).(4)Among the four haplotypes in southwest Chinese Han population, which are composed of the two SNPs of PGC-1αgene, the most common were G C and A C, frequency of which between the two groups were 0.460/0.515 and 0.278/0.285 respectively(P>0.05). The haplotype frequencies of A T were 0.185/0.077(P<0.05),There were significant differences between T2DM cases and controls subjects. Conclusions(1) The PCR-RFLP technique is a method which can conveniently detect SNP with more specificity, stability , reproducibility and reliability.(2)The study discovered the genotypes distribution and haplotypes distribution of the two SNPs of PGC-1αgene in Han people of southwest China, which would supply valuable data for further studies on the association of SNPs in PGC-1αgene with the pathophysiology of T2DM.(3)The study indicated a possible involvement of SNP rs8192678 in PGC-1αgene in the development of T2DM among southwest Chinese Han population.
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