Objective: Earlier, GLIS3 gene polymorphisms have been shown to be associated with the development of maturity onset diabetes of the young (MODY). We screened GLIS3 gene sequences among patients with MODY to identify probably pathogenic variants by whole-exome sequencing. We estimated frequency of rare single-nucleotide variants in the coding region of GLIS3 in a Caucasian population and among individuals with carbohydrate metabolism disorders in Russia.
Results: We identified 15 single-nucleotide variants in GLIS3. Three rare variants (minor allele frequency < 1%) rs806052, rs143051164, and rs149840771 were genotyped in 126 cases of MODY, in 188 patients with type 2 diabetes mellitus (DM2), and 564 randomly selected Caucasian individuals in Russia. A heterozygous rs806052 variant was identified in one patient with DM2; c.1270T frequency was 0.003. Prevalence of rs143051164 c.844G was 0.003 in the control population and 0.004 and 0.003 in MODY and DM2 samples, respectively. Prevalence of rs149840771 c.2096A was 0.003 and 0.004 in the control population and among MODY patients, respectively. In DM2 patients, rs149840771 c.2096A was not identified. We did not detect any associations of rs806052, rs143051164, and rs149840771 with carbohydrate metabolism disorders among patients with MODY and DM2 in Russia.
Keywords: GLIS3; MODY; Maturity onset diabetes of the young; Population; Single-nucleotide polymorphism; Type 2 diabetes mellitus; rs143051164; rs149840771; rs806052.