Povezanost polimorfizama gena značajnih za diferencijaciju i aktivaciju mrkog masnog tkiva sa indeksom telesne mase, glikemijom i lipidnim statusom adolescenata

Abstract

Dečija i adolescentna gojaznost predstavlja sve veći problem savremenog društva, a udružena je sa brojnim poremećajima među kojima su najčešći metabolički sindrom i dijabetes tipa II. Imajući u vidu da mrko masno tkivo ima značajnu ulogu u regulaciji telesne mase, metabolizmu glukoze, lipida i energetskoj homeostazi, u ovom istraživanju rađena je genotipizacija pet jednonukleotidnih polimorfizama u genima značajnim za diferencijaciju i aktivaciju mrkog masnog tkiva (rs12409277 u genu za PRDM16, rs1561589 u genu za CtBP2, rs3856806 u genu za PPARγ, rs8192678 u genu za PGC-1α i rs 6265 u genu za BDNF). Cilj istaživanja je bio odrediti učestalosti odgovarajućih genotipova i alela, te ispitati postoji li statistički značajna povezanost između odabranih genotipova sa vrednostima indeksa telesne mase, glikemije i lipidnih parametara u ispitivanom uzorku. Istraživanje je obuhvatilo 308 adolescenata oba pola, uzrasta 15 godina koji su pregledani u okviru Jugoslovenske studije prekursora ateroskleroze kod školske dece. Uzorak je selektovan slučajnim odabirom 217 adolescenata normalnog indeksa telesne mase (ITM≤85. percentila) i 91. adolescenta čiji indeks telesne mase prelazi 85 percentila (preuhranjeni i gojazni). Genotipizacija polimorfizama BDNF, PPARG, i PPARGC1A gena rađena je PCR-RFLP metodom. Detekcija genotipova za polimorfizme PRDM16 i CtBP2 vršena je primenom PCR-a u realnom vremenu upotrebom TaqMan®SNP eseja za genotipizaciju. Rezultati ove studije ukazuju da su nosioci GG genotipa u okviru BDNF polimorfizma imali statistički značajno više vrednosti glikemije u odnosu na nosioce GA+AA genotipova (p=0,010). Takođe, u okviru polimorfizama PPARG gena uočene su više vrednsoti glikemije kod devojčica nosioca CC genotipa u odnosu na nosioce CT+TT genotipa (p=0.030). Statistički značajne razlike u vrednostima lipidnih parametara u odnosu na genotipove zapažene su kod svih ispitivanih polimorfizama izuzev rs6265 polimorfizma. Nije uočena asocijacija ni jednog od analiziranih polimorfizama sa vrednostima indeksa telesne mase kako na ukupnom uzorku, tako ni u grupi normalno uhranjenih i preuhranjenih i gojaznih adolescenata.

Childhood and adolescent obesity is becoming a major health problem of modern society, and is associated with numerous disorders including metabolic syndrome and type II diabetes. Since brown adipose tissue has important role in regulation of body weight, glucose and lipid metabolism as well as in energy homeostasis, in this research we performed genotypization of five single nucleotide polymorphisms in genes significant for differentiation and activation of brown adipose tissue (rs12409277 in gene for PRDM16, rs1561589 in gene for CtBP2, rs3856806 in gene for PPARγ, rs8192678 in gene for PGC-1α and rs6265 in gene for BDNF). The aim of the study was to determine the frequency of corresponding genotypes and alleles, as well as to determine whether there is a statistically significant association between the selected genotypes and values of body mass index, glycaemia and lipid parameters in the examined sample. The study included 308 adolescents of both genders, 15 years of age who participated in Yugoslav Study of the Precursors of Atherosclerosis in School Children. Subjects were randomly selected including 217 adolescents of normal body mass index (BMI ≤85. percentile) and 91 adolescents with BMI>91. percentile (overweight and obese). BDNF, PPARG, and PPARGC1A genotyping was performed by PCR-RFLP method. Genotype detection of PRDM16 and CtBP2 polymorphismswas examined by Real Time PCR using TaqMan®SNP genotyping assays. The results of this study indicate that carriers of GG genotype within the BDNF polymorphism had statistically significantly higher glycemic values compared to carriers of GA+AA genotypes (p=0.010). Also, within the PPARG polymorphism, higher mean values of glycemia were observed in girls carrying the CC genotype compared to carriers of the CT+TT genotypes (p=0.030). Statistically significant difference in values of lipid parameters depending on genotypes were observed in all examined polymorphism sexcept in rs6265 polymorphism. No association of any analyzed polymorphisms was observed with body mass index neither in total examined sample, nor in the group of normal, overweight and obese adolescents.