PGC-1α is an important regulatory factor for energy and glucose metabolism. Therefore, we investigated whether the PGC-1α genotype (rs10517030 and rs10212638) affects the incidence of type 2 diabetes mellitus (T2DM) and sought to explain the interactions between their variants and nutrient intake on the development of T2DM.SUBJECTS/METHODS:
Subjects aged 40-65 years of both genders were from the Ansung/Ansan cohorts (8842 adults) in Korea. Associations of PGC-1α variants rs10517030 and rs10212638 with T2DM were analyzed in a dominant genetic model, and were tested for interactions of genotypes and nutrients with T2DM risk. It was adjusted for covariates related to glucose metabolism.RESULTS:
Three variants, rs10517030, rs10517032 and rs10212638, were positively associated with T2DM prevalence. Single-nucleotide polymorphisms, rs10517030 and rs10517032, had strong association (r2 = 0.963). In the glucose tolerance tests, odds ratios (ORs) for serum glucose levels at 120 min were higher for subjects who were in the minor-allele group (minor allele homozygotes and heterozygotes) than for the major-allele group (major allele homozygotes) for rs10517030 variants. Serum insulin levels at 60 min had a lower ORs in the minor-allele group of rs10517030 variants. The interaction between energy intake and PGC-1α rs10517030 variants also affected T2DM risk. PGC-1α minor alleles were linked to T2DM prevalence and homeostasis model assessment estimate of insulin resistance (HOMA-IR) only in the low-energy groups, and HOMA-B was significantly negatively associated with the minor-allele group of PGC-1α rs10517030 variants, only in the low-energy-intake groups.CONCLUSIONS:
These data suggest that Koreans with the minor alleles of PGC-1α rs10517030, rs10517032 and rs10212638 are at greater risk of T2DM, and that a low-energy diet is more protective against the development of T2DM in subjects with the major alleles of rs10517030 and rs10517032.