The study of PGC-1 gene polymorphism in relation with insulin resistance in people with metabolic syndrome / Монголын Анагаах Ухаан

ABSTRACT

INTRODUCTION: The PGC-1 gene is located on chromosome 4 p.15.1 in humans and encodes a protein containing 798 amino acids. As PGC-1a regulates multiple aspects of energy metabolism, it is not surprising that PGC-1a has been found to be deregulated in several pathological conditions. Might be associated with type 2 diabetes because PGC-1, besides being a coactivator of PPAR a and b, has a critical role in glucose uptake and adaptive thermogenesis. Addition, a common polymorphism of the PGC-1 gene Gly482Ser, which apparently reduces PGC-1 activity, has been linked to increased risk of type 2 diabetes. Association has also been reported between the Gly482Ser substitution and insulin resistance in Japanese subjects. Similar reduction of PGC-1 expression was also observed in the adipose tissue of insulin-resistant and morbidly obese individuals. Previous studies have reported significant association between the Gly482Ser missense mutation of the PGC-1 gene and reduced insulin sensitivity in obese subjects. This association resulted independent from all other known modulators of insulin resistance, and suggests a primary role for the PGC-1 gene on the genetic susceptibility to insulin resistance in obesity.GOAL To study the presence of PGC-1 gene Gly482Ser polymorphism in people with Metabolic syndrome and study the relation to serum insulin level and insulin resistance.MATERIALS AND METHODS: The study population comprised 302 unrelated Mongolian subjects (158 with metabolic syndrome and 144 controls). MS was determined by IDF (International Diabetes Federation) criteria. The genotypes for polymorphism of candidate gene related to MS were determined using a RFLP analysis of the MspI digest of the PCR product. We determined serum insulin by ELISA, using Eucardio Company’s kit and insulin resistance was defined by the HOMA-IR formula.RESULT: 33.4% (48) of control group had GG, 47.2% (68) had GS and 19.4% (28) had SS genotypes of PGC-1 gene. 51.9% (82) of people with MS had GG, 35.4% (56) had GS and 12.7% (20) had SS genotypes. The prevalence of G allele in people with MS was 69.6%, which is much higher than healthy group. Insulin and HOMA-IR of MS group were higher than compared to healthy group (p<0.05). HOMA-IR was lower in people with GS genotype comparing to GG and SS in people with metabolic syndrome. CONCLUTIONS 1. People with MS had higher levels of serum insulin (p<0.013) and insulin resistance (p<0.004) in compare to healthy people. 2. 69.6 percentages of the people with MS had G allele, which was 2.2 times more than those without metabolic syndrome.3. People with MS who carry SS genotype had higher levels of serum insulin (p=0.02) and insulin resistance (p=0.008) than people without MS. Insulin resistance was significantly correlated (r=0.302, p<0.001) with hypertension in people with G allele.