ABSTRACT
Introduction: The metabolic syndrome (MS) is characterized by central obesity, hypertriglyceridemia,low high-density lipoprotein (HDL), increase blood pressure and raise fasting plasma glucose. ThePGC-1α gene is located on chromosome 4 p.15.1 in humans and encodes a protein containing 798amino acids. The protein encoded by this gene is a transcriptional coactivator that regulates thegenes involved in energy metabolism. PPARγ, a coactivator molecule recently identified based on itsability to interact with PPARγ, is involved in many important metabolic processes, including adaptivethermogenesis, mitochondrial biogenesis and fatty acid β–oxidation.Goal: To study the frequency of PGC-1α Gly482Ser polymorphism in people with MS in relation to therisk factors of the MS.Materials and methods: The study population comprised 302 unrelated Mongolian subjects (158 withmetabolic syndrome and 144 controls). The genotypes for polymorphism of candidate gene related toMS were determined using a RFLP analysis of the MspI digest of the PCR product.Result: From the control group, 33.4% (48) had GG, 47.2% (68) had GS and 19.4% (28) had SSgenotypes. 51.9% (82) of people with MS had GG, 35.4% (56) had GS and 12.7% (20) had SSgenotypes. The prevalence of G allele in people with MS was 69.6%, which is much higher than healthygroup. Comparing PGC-1α Gly482Ser GG, GS and SS genotypes with systolic arterial blood pressurerevealed statistically significant difference which was higher among subjects with GG genotype. Theblood pressure of people with MS and carrying GG genotype of PGC-1α Gly482Ser polymorphismwas significantly increased 2.35 times than people without MS.Conclusions:1. 69.6 percentages of the people with MS had G allele and 2.2 times more than those withoutmetabolic syndrome.2. We determined that the odds ratio for the high blood pressure and it was 2.35 times higher inpeople with GG allele of Gly482Ser carriers than GS and SS alleles carriers (OR = 2.35, p =0.012).
ABSTRACT
Objective To investigate the association of PGC-1 α gene single nucleotide polymorphisms (SNPs) with type 2 diabetes mellitus in Southern China Han population. Methods 350 patients with type 2 diabetes mellitus and their parents and 366 normal Han volunteers were recruited in the study. Their blood specimens were collected to extract the genornic DNA. Thr394Thr(G/A), Gly482Ser(G/A), Thr528Thr(A/G) and Thr612Met (C/T) genotypes were identified by PCR-RFLP and DNA direct sequencing. The possible association was analyzed between diabetic patients with the specific cSNPs and their haplotypes by case-control and haplotype relative risk (HRR) and transmission disequilibrium test (TDT) methods. Results (1) The case- control study indicated that G and A allele frequencies of PGC-1 α gene Gly482Ser variant were 0.589, 0.411 in type 2 diabetic group and 0.687, 0.313 in normal group respectively (X<'2> = 15.076, P < 0.01). The allele frequencies of Thr394Thr, Thr528Thr, Thr612Met polymorphisms did not show significant difference between twogroups respectively (all P > 0.05). The distributions of Thr394Thr-Gly482Ser-Thr528Thr haplotypes in the diabetic group were significanly different from the controls (X<'2> = 40.2, P < 0.05) and had a linkage disequilibrium with type 2 diabetes mellitus (t = 2.503, P < 0.05). (2) The family-basod studies showed that 482A allele was transmitted more significantly both via TDT and extended TDT from heterozygous parents to patients than expected respectively (all P < 0.05). HRR also supported that the 482A allele was more often transmitted to patients than predicted by chance (X<'2> = 7.217, P = 0.007, HRR = 1. 450). TDT analyses of haplotypes suggested that the frequencies of 394A-482A-528A-612C,394A-482A-528A-612T, 394A-482A-528G-612C and 394A-482A-528G- 612T haplotypes significantly deviated from 0.5 (P < 0.05 or P < 0.01). Conclusion In Southern China Hanpopulation, type 2 diabetes mellitus is associated with the Gly482Ser variant of PGC-1α gene, and Thr394Thr (G/ A) variant of PGC-1α gene appears to play an auxiliary role in this association.