ACTA ENDOCRINOLOGICA (BUC)

Background. The peroxisome proliferatoractivated receptor-γ co-activator 1-α (PPARGC1A), a key transcription factor involved in the control of metabolism and energy homeostasis, is an important biological and positional candidate of the metabolic syndrome. Association studies of its polymorphisms, however, yielded inconsistent sometimes conflicting results, pointing to important ethnic differences, which call for replication in various populations. Objective. In order to study its most common - potentially functional - polymorphism Gly482Ser (rs8192678), we carried out a case-control study in a central Romanian population. Material and methods. Two hundred and ninety six patients affected by the metabolic syndrome diagnosed according to the International Diabetes Federation proposed criteria and 166 middle-aged control subjects have been investigated. Genotyping was done by PCR-RFLP, using the restriction enzyme MspI. Results. While the G(Gly)/A(Ser) allele frequencies (66.89/33.11 vs. 71.68/28.31 %) and GG/GA/AA genotype distribution (45.27-43.24-11.48 vs. 54.21-34.93-10.84 %) differed in the metabolic syndrome and control group, the risk of developing the metabolic syndrome did not reach the limit of statistical significance (OR=1.43; p=0.06, CI 95%: 0.97-2.09). Metabolic parameters in the two study groups did not show significant differences according to the genotype (p>0.05). Conclusion. rs8192678 could be a functional polymorphism contributing to the development of the metabolic syndrome, but probably its effect is minor, and might depend on gene–gene and gene-environment interactions. Clarification of very small effects would require larger sample sizes.

The nuclear receptor coding PPARγ2 (PEROXISOME PROLIFERATORACTIVATED RECEPTOR-GAMMA; *601487) gene influences the lipid and carbohydrate metabolism via multiple pathways and is a candidate for the metabolic syndrome. In this paper we studied the relationship of the CCG (Pro) → GCG (Ala) polymorphism of the gene with the metabolic syndrome diagnosed according to the criteria recommended by the International Diabetes Federation (IDF) in 2005, in a population from central Romania. We have carried out a case-control study on 144 patients and 73 control subjects. Routine biochemical assays have been carried out, fasting insulinemia was measured by ELISA, and insulin sensitivity was assessed by calculating the HOMA and QUICKI indices. Genetic analysis was done by PCR followed by digestion with the restriction enzyme BstU I. The results show that the Pro12 allele had a higher frequency in the group of patients as compared to the healthy controls (76 vs. 65.7%, p<0.05). The risk for developing the metabolic syndrome in the presence of the Pro12 allele in a homozygous combination was found to be low but statistically significant (PP vs. PA + AA: OR = 1.98, CI 95% 1.04 -3.78, p = 0.046). In conclusion, in the local population, the Pro12 allele of the PPARG2 gene seems to contribute to the hereditary predisposition of the metabolic syndrome diagnosed according to the recommendations of the IDF, most likely as part of a polygenic system. Probably the absence of the protective Ala12 allele increases the risk for developing the disease.