THE ROLE OF POLYMORPHISMS OF GLUTAMATE-CYSTEINE LIGASE IN TYPE 2 DIABETES MELLITUS SUSCEPTIBILITY IN KURSK POPULATION
Relevance. Glutamate-cysteine ligase (GCL) is the first enzyme of the glutathione cycle, intra- and extracellular antioxidant, whose impaired metabolism plays an important role in type 2 diabetes (T2D) pathogenesis. Problem. The authors study associations of the GCLC (-129 C>T, rs17883901)and GCLM (-588 C>T, rs41303970) polymorphisms with the risk of T2D development and pro/antioxidant status in the population of Kursk region. Materials and methods. The study groups included 700 T2D patients (269 males and 431 females) of mean age 59,24±8,77 who were admitted to the endocrinological department of Kursk Emergency Hospital from November 2015 to May 2017, and 718 healthy subjects (311 males and 407 females) of mean age 58,61±7,65. Genotyping of GCLC (-129 C>T, rs17883901)and GCLM (-588 C>T, rs41303970) polymorphisms was performed by PDAF, PCR, real-time discrimination of alleles using TaqMan probes. Statistical analysis was performed with the use of the on-line software SNPStats. Results. There was no difference in genotype distribution among type 2 DM and control subjects in GCLC and GCLM genes (р>0,05). Sex-stratified analysis revealed association of T/T genotype of GCLC gene with an increased risk of T2D development exclusively in males (OR 1,65, 95%CI 1,05-2,61, p=0,03) and particularly in a subgroup of smokers (OR 2,36, 95%CI 1,19-4,65, p=0,01); they also showed an increased frequency of rare allele T of GCLC gene(OR 1,69, 95%CI 1,11-2,58, p=0,02), and elevated plasma levels of oxidized glutathione GSSG and hydrogen peroxide. Conclusions. Smoking and rare allele T of the GCLC gene (rs17883901) increase susceptibility to T2D in males and contribute to formation of imbalance in pro- and antioxidant systems.