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ntroduction: The enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) catalyzes the con-version of the hormonally inactive cortisone to active cortisol, thus facilitating glucocorticoid receptor activation in target tissues. Increased expression of 11β-HSD1 in adipose tissue has been associated with obesity and insulin resistance. In this study, we investigated the association of two 11β-HSD1 gene (HSD11B1) polymorphisms with the metabolic syndrome (MetS) and its characteristics in the Bosnian population. Materials and methods: The study included 86 participants: 43 patients diagnosed with MetS and 43 healthy controls. Subjects were genotyped for two HSD11B1 gene polymorphisms: rs846910: G>A and rs45487298: insA, by the high resolution melting curve analysis. Genotype distribution and an influence of genotypes on clinical and biochemical parameters were assessed. Results: There was no significant difference in the mutated allele frequencies for the two HSD11B1 gene polymorphisms between MetS patients and controls. In MetS patients, no significant associati-ons between disease-associated traits and rs45487298: insA were found. Regarding rs846910: G>A variant, heterozygous patients (G/A) had significantly lower systolic (P = 0.017) and diastolic blood pressure (P = 0.015), lower HOMA-IR index (P = 0.011) and higher LDL-cholesterol levels (P = 0.049), compared to the wild-type homozygotes. In the control group, rs45487298: insA polymorphism was associated with lower fasting plasma insulin levels (P = 0.041), lower homeostasis model asses-sment insulin resistance (HOMA-IR) index (P = 0.041) and lower diastolic blood pressure (P = 0.048). Significant differences between rs846910: G>A genotypes in controls were not detected. Haplotype analysis confirmed the association of rs45487298: insA with markers of insulin resistance in the con-trol subjects. Conclusions: Our results indicate that a common rs45487298: insA polymorphism in HSD11B1 gene may have a protective effe

Uvod: Inzulinska rezistencija je obilježena oslabljenim tkivnim odgovorom na djelovanje inzulina, a udružena je s pretilošću, šećernom bolesti tipa 2, metaboličkim sindromom, lipodistrofijama, sindromom policističnih jajnika (engl. polycystic ovary syndrome, PCOS) i kroničnom infekcijom. Inzulinska rezistencija je prisutna kod 50-70% bolesnica s PCOS. Peroksizomni proliferatorom aktivirani receptor gama (engl. peroxisome proliferator-activated receptor γ, PPARγ) je jezgreni receptor koji kontrolira transkripciju gena uključenih u metabolizam slobodnih masnih kiselina i lipogenezu, a važan je za diferencijaciju i preživljenje adipocita. Cilj ovoga probnog istraživanja bio je ispitati povezanost polimorfizama Pro12Ala i His477His PPARG gena s inzulinskom rezistencijom kod bolesnica s PCOS. Bolesnice i metode: U istraživanju je sudjelovalo 69 bolesnica s PCOS. Metodom PCR-RFLP analizirane su frekvencije genotipova. Glukoza natašte i glukoza nakon oralnog testa opterećenja glukozom (engl. oral glucose tolerance test, OGTT), inzulin, hsCRP (engl. high sensitivity C-reactive protein), tjelesna masa, visina, opseg struka, sistolični i dijastolični krvni tlak, indeks tjelesne mase (engl. body mass index, BMI) i indeks procjene modela homeostaze (engl. homeostasis model assessment, HOMA) izmjereni su rutinskim metodama ili su izračunati iz podataka. Rezultati: Pronađena je značajna povezanost između alela Ala polimorfizma Pro12Ala i nižeg BMI (P = 0,040) te između alela T polimorfizma His477His i niže koncentracije hsCRP (P = 0,047). Polimorfizmi Pro12Ala i His477His pokazali su značajnu neravnotežu povezanosti (engl. linkage disequilibrium) (D' = 0,727). Analiza diplotipova nije pokazala da postoji povezanost. Zaključak: U ovom preliminarnom istraživanju pronašli smo značajnu povezanost između alela Ala polimorfizma Pro12Ala i nižeg BMI te alela T polimorfizma His477His i nižeg hsCRP. Međutim, niti jedan od ova dva polimorfizma, pojedinačno ili u kombinaciji (diplotip), nij, Background: Insulin resistance is characterized by attenuated response of tissues to insulin action and is associated with obesity, type 2 diabetes mellitus, metabolic syndrome, lipodystrophies, polycystic ovary syndrome (PCOS) and chronic infection. Insulin resistance is present in 50%—70% of PCOS patients. Peroxisome proliferator-activated receptor γ (PPARγ) is a nuclear receptor which controls transcription of genes involved in free fatty acid uptake and lipogenesis, and is essential for diferentiation and survival of adipo-cytes. The aim of our pilot study was to investigate the association between Pro12Ala and His477His polymorphisms in PPARG gene with insulin resistance in PCOS patients. Patients and methods: The study included 69 PCOS patients. Genotype frequencies were analyzed by PCR-RFLP methods. Fasting glucose and glucose after oral glucose tolerance test, insulin, and high sensitivity C-reactive protein (hsCRP), body mass, height, waist circumference, systolic and diastolic blood pressure, body mass index (BMI) and homeostasis model assessment (HOMA) index were measured by routine methods or calculated from the findings obtained. Results: A signi;cant association was found between the Ala allele of the Pro12Ala polymorphism and lower BMI (P = 0.040) and between the T allele of the His477His polymorphism and lower hsCRP (P = 0.047). The Pro12Ala and the His477His polymorphisms were in considerable linkage disequilibrium (D' = 0.727). Diplotype analysis showed no association. Conclusions: In our preliminary study, we found a significant association between the Ala allele of the Pro12Ala polymorphism and lower BMI, and between the T allele of the His477His polymorphism and lower hsCRP. However, none of the two polymorphisms, individually or in combination (diplotype), was associated with fasting plasma insulin and glucose concentrations and HOMA index that are characteristic of insulin resistance. We therefore conclude that the polymorphisms investigated a

Inzulinska rezistencija je stanje poremećene sposobnosti odgovora na djelovanje inzulina. Najčešći osnovni uzrok je središnja pretilost, iako je primarna inzulinska rezistencija moguća i u osoba s normalnom težinom. Suvišno abdo-minalno masno tkivo otpušta povećane količine faktora tumorske nekroze α i slobodnih masnih kiselina, što izravno utječe na inzulinsko signaliziranje, smanjuje preuzimanje glukoze u mišićima, dovodi do pretjerane sinteze trigliceri-da i izaziva glukoneogenezu u jetri. Ostali čimbenici za koje se pretpostavlja da igraju ulogu u inzulinskoj rezistenciji su adiponektin (sniženje), leptin, IL-6 i neki drugi adipokini. Smatra se da je obična pretilost poligenog podrijetla uz utjecaj "pretilogene" okoline - povećan unos hrane i nedostatak tjelesne aktivnosti. Današnja visoka učestalost pretilosti mogla bi se objasniti evolucijskim pritiskom za odabir gena koji promiču pohranu masti za preživljenje u vrijeme gladovanja. Inzulinska rezistencija je prisutna zajedno sa središnjom pretilosti, hipertenzijom i dislipidemijom, koje se skupno označavaju kao metabolički sindrom. Ove pojavnosti predstavljaju snažne čimbenike rizika za šećernu bolest tipa 2 i kardiovaskularnu bolest., Insulin resistance is a state of impaired responsiveness to insulin action. The most common underlying cause is central obesity although primary insulin resistance in normal-weight individuals is also possible. Excess abdominal adipose tissue has been shown to release increased amounts of tumor necrosis factor α and free fatty acids, which directly affect insulin signaling, diminish glucose uptake in the muscle, drive exaggerated triglyceride synthesis and induce gluconeogenesis in the liver. Other factors presumed to play a role in insulin resistance are adiponectin (a decrease), leptin, IL-6 and some other adipokines. Common obesity is thought to be of polygenic origin with influence of "obesogenic" environment, i.e. increased food intake and the lack of physical activity. Today's high prevalence of obesity could be explained by evolutionary pressure for selection of genes promoting fat storage to survive in starvation. Insulin resistance frequently coexists with central obesity, hypertension and dyslipidemia, which have collectively been denoted as metabolic syndrome. These manifestations represent strong risk factors for diabetes mellitus type 2 and cardiovascular disease.