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Objective: To study the baseline distribution of polymorphisms in the promoter of peroxisome proliferators activated receptor co-activator 1 (PPARGC1A) gene in ethnic Hans from Beijing, and to assess their association with type 2 diabetes (T2DM)., Methods: A 2-stage study was designed. Firstly, the promoter region of PPAGC1A gene was screened with PCRRFLP in a small population (n=216, T2DM/control: 104/112), which was followed by a replication study of a larger group (n=1546, T2DM/control: 732/814). Fasting plasma glucose, insulin, blood lipid, height, weight, waist circumference, and blood pressure were measured in all subjects. Potential association was assessed by logistic regression. Linkage disequilibrium and haplotype analysis were conducted with Haploview software., Results: Five polymorphisms were identified with Sanger sequencing, among which T-2120C (rs3755857), -1999C/G (rs2946386) and -1437T/C (rs2970870) were included for genotypic analysis based on their moderate levels of heterozygosity. No significant difference was found between the two groups. When adjusted for age and gender confounding, we have combined the OR values from population 1 and population 2 based on Mantel-Haenszel fixed model, and recognized a mild contribution of C allele of -1999C/G (rs2946386) to the 1.18-fold risk of T2DM (P=0.03, OR=118). No haplotype was associated with T2DM after permutation correction., Conclusion: The C allele of -1999C/G ( rs2946386) in the promoter region of the PPARGC1A gene is mildly associated with T2DM. Variations in the promoter region of the PPARGC1A gene seem not to confer the risk of T2DM in our population.

The application of next generation sequencing (NGS) technique has a great impact on epigenetic studies. Coupled with NGS, a number of sequencing-based methodologies have been developed and applied in epigenetic studies, such as Whole Genome Bisulfite Sequencing (WGBS), Reduced Representation Bisulfite Sequencing (RRBS), Methylated DNA Immunoprecipitation Sequencing (MeDIP-seq), Chromatin Immunoprecipitation-Sequencing (ChIP-seq), TAB-seq (Tet-assisted Bisulfite Sequencing), Chromosome Conformation Capture Sequencing (3C-seq) and various of 3C-seq de-rivatives, DNase1-seq/MNase-seq/FAIRE-seqand RNA Sequencing (RNA-seq). These new techniques were used to iden-tify DNA methylation patterns and a broad range of protein/nucleic acid interactions, and to analyze chromatin conforma-tion.With these new technologies, researchers have gained a broader view and better tools to investigate the distributions and dynamic changes of epigenetic markers affected by both internal and external factors. The principles and characteristics of major applications of NGS technologies on epigenetics were summarized; and the recent advances and the future direc-tions in NGS-based epigenetic studies were further discussed.