A genetic variation in the PGC-1 gene could confer insulin resistance and susceptibility to Type II diabetes

Abstract

Aims/hypothesis. Peroxisome proliferator activated receptor γ coactivator-1 (PGC-1), a transcriptional coactivator of the nuclear receptor PPARγ, plays a role in adaptive thermogenesis and insulin sensitivity. Plasma fasting insulin has been linked to the chromosomal region where the PGC-1 gene is located. Thus, PGC-1 can be viewed as a functional and positional candidate for the susceptibility gene for Type II (non-insulin-dependent) diabetes mellitus. Methods. After screening the PGC-1 gene for single nucleotide polymorphisms (SNPs), we performed an association study using the newly detected SNPs in 537 Type II diabetic patients and 417 non-diabetic subjects. Results. We found three relatively frequent SNPs in the PGC-1 gene (IVS4-11T > C, Thr394Thr and Gly482Ser). There were significant differences in fasting insulin (Gly/Gly; 37.7 ± 1.43, Gly/Ser; 40.2 ± 1.21, Ser/Ser; 44.3 ± 1.82 pmol/l, p = 0.018) and insulin resistance index (Gly/Gly; 1.48 ± 0.06, Gly/Ser; 1.56 ± 0.05, Ser/Ser; 1.75 ± 0.08, p = 0.027) according to the genotype of the Gly482Ser polymorphism. The Thr394Thr - Gly482Ser haplotype was associated with Type II diabetes (p = 0.00003). Conclusion/interpretation. The results of this study suggested that the PGC-1 gene might be implicated in the pathogenesis of Type II diabetes.