Introduction: The enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) catalyzes the conversion of the hormonally inactive cortisone to active cortisol, thus facilitating glucocorticoid receptor activation in target tissues. Increased expression of 11beta-HSD1 in adipose tissue has been associated with obesity and insulin resistance. In this study, we investigated the association of two 11beta-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 associations between disease-associated traits and rs45487298: insA were found. Regarding rs846910: G > Avariant, 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 assessment 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 control subjects.
Conclusions: Our results indicate that a common rs45487298: insA polymorphism in HSD1181 gene may have a protective effect against insulin resistance.
Uvod:: Enzim 11β-hidroksisteroidne dehidrogenaza tipa 1 (engl. 11β-hydroxysteroid dehydrogenase type 1, 11β-HSD1) katalizira pretvorbu hormonalno neaktivnog kortizona u aktivan kortizol te na taj način omogućuje aktivaciju receptora glukokortikoda u ciljnim tkivima. Povišena ekspre sija 11β-HSD1 u adipoznom tkivu povezuje se s pretilošću i inzulinskom rezistencijom. U ovom istraživanju ispitivali smo povezanost dvaju polimorfizma gena 11β-HSD1 (HSD11B1) s metaboličkim sindromom (MetS) i njegovim karakteristikama u Bosanskoj populaciji.
Materijali i metode:: U istraživanje je bilo uključeno 86 ispitanika: 43 bolesnika s dijagnozom metaboličkog sindroma i 43 zdrava ispitanika. Načinjena je genotipizacija analizom krivulje taljenja DNK visoke rezolucije za dva polimorfizma gena HSD11B1: rs846910:G>A i rs45487298:insA. Ispitana je i raspodjela genotipova te utjecaj genotipova na kliničke i biokemijske parametre.
Rezultati:: Nije nađena statistički značajna razlika u frekvencijama mutiranih alela za dva polimorfizma gena HSD11B1 između skupina bolesnika s MetS i kontrolnih ispitanika. Kod bolesnika s MetS nisu primijećene statistički značajne veze između značajki povezanih s bolešću i rqs45487298: insA. Što se tiče polimorfizma rs846910: G>A, heterozigotni su bolesnici (G/A) imali statistički značajno niži sistolički (P = 0,017) i dijastolički (P = 0,015) krvni tlak, niži HOMA-IR indeks (P = 0,011) i višu koncentraciju LDL-kolesterola (P = 0.049) u usporedbi s divljim tipom. U skupini zdravih ispitanika polimorfizam rs45487298: insA bio je povezan s nižim koncentracijama inzulina natašte (P = 0,041), nižim homeostatskim modelom procjene inzulinske rezistencije - HOMA-IR indeksom (P = 0,041) i nižim dijastoličkim tlakom (P = 0,048). Značajne razlike između rs846910: G>A genotipova kod kontrola nisu nađene. Analiza halotipova potvrdila je povezanost rs45487298: insA s biljezima inzulinske rezistencije kod kontrolnih ispitanika.
Zaključak:: Naši rezultati pokazuju da čest polimorfizam rs45487298: insA gena HSD11B1 može imati zaštitni učinak protiv inzulinske rezistencije.