Polymorphic markers of the genes of diabetes mellitus in patients with acromegaly

Zhulidova Anna Yurievna, Filimonova Alla Yurievna, Tverdova Lyudmila Vasilyevna, Nikiforov Alexander Alekseevich, Uryasev Oleg Mikhailovich, Dubinina Inessa Ivanovna

Backgraund: Acromegaly is a severe neuroendocrine disease, which is burdened by the development of comorbid pathology, in particular diabetes. Currently, the diagnostic practice is being implemented studies of candidate genes, and their mutations lead to the development of carbohydrate metabolism disorders. Aims: to study the prevalence of impaired glucose metabolism in patients with acromegaly, to investigate the distribution of allele frequencies and the linkage of polymorphic markers of gene Pro12Ala PPARG, PPARG2 Pro12Ala gene, gene Gly482Ser PPARGC1A, PPARGC1B gene Ala203Pro, Arg223Glr gene LEPR, A23525T gene FTO, PPARG C1431T gene with the development of secondary diabetes and obesity in patients with acromegaly. Materials and methods: The register of the Ryazan region consists of 65 patients with acromegaly. It includes 56 (86.1%) women, 9 (13.9%) men aged 56.4±1.2 years. In the endocrinology Department of GBU RO Regional clinical hospital in genetic research involved 35 patients. Group 1 consisted of 13 patients with acromegaly and secondary diabetes mellitus ("acromegaly + SD"), group 2 −10 patients with acromegaly without diabetes ("acromegaly"), group 3 – 12 patients with type 2 diabetes (SD 2). The genetic polymorphism of diabetes mellitus and obesity (PPARG, pparg2, PPARGC1A, PPARGC1B, LEPR, FTO) was determined by the allele of specific PCR with subsequent electrophoretic separation of amplification products. Results: When analyzing the distribution of polymorphisms of genes in the examined groups (acromegaly +, acromegaly, type 2 diabetes), significant differences (p≤0,05) detected by the Gly482Ser genotype at the PPARGC1A gene (mutation 1aPPARG). In the study of this mutation, the predominance of the Gly482Ser genotype in the group of patients with type 2 diabetes (10 people – 83.4%) is noteworthy. The number of mutant alleles 482Ser in the PPARGC1A gene (mutation 1aPPARG), 203Pro PPARGC1B (mutation 1bPPARG) tends to increase in the group of patients with type 2 DM (50% and 25%). When comparing the frequency distribution of alleles in the study groups, no significant differences were found. Conclusions: The analysis of the register confirms the high prevalence of carbohydrate metabolism disorders in patients with acromegaly. The comparative analysis of the frequency distribution of genetic alleles of diabetes mellitus showed no differences in patients with isolated acromegaly and a combination of acromegaly and diabetes. According to the study of insulin resistance in patients with acromegaly is not associated with genomic mutations, and is the result of the actions of GH on glucose metabolism.

Keywords:Acromegaly; comorbidity; diabetes; genetic markers