Koliada O. The role of mutations in the LRRK2, SNCA and GBA genes and polymorphic variants of the CYP1A1, GSTM1 and APOE genes, and telomere length in the risk of Parkinson's disease

With the objective to investigate the role of mutations and polymorphic variants of a number of genes, as well as telomere length in the development of Parkinson's disease, prospective study was conducted on the basis of the State Institution Dmitry F. Chebotarev Institute of Gerontology of the National Academy of Medical Sciences of Ukraine with the participation of 216 patients with Parkinson's disease and 300 healthy individuals of the control group. The study material was blood samples and buccal epithelium of patients diagnosed with Parkinson's disease and clinically healthy people. We examined 216 patients with Parkinson's disease (106 men and 110 women), mean age 63.1 ± 1.3 (38–78) years, with a mean disease duration of 7.6 ± 0.33 years. The c.6055G> A mutation in the LRRK2 gene is a factor in the genetic predisposition to Parkinson's disease and is found in 1.86 % of patients with this disease. Mutations c.1448T> C and c.1226A> G in the GBA gene are factors of genetic predisposition to Parkinson's disease, they were found in 1.86 % and 1.39 % of patients with this disease, respectively. Carriers of the c.209G> A mutation in the SNCA gene were not detected in the control group and among patients. The association of the risk of developing Parkinson's disease with the carrier of allelic variants of the CYP1A1 gene has been revealed. The presence of the c.1384G allele increases the risk by 1.76 (CI 95 % 1.30–2.39) times. The association of the risk of Parkinson's disease developing with the carrier of a homozygous deletion in the GSTM gene was revealed, which increases the risk of the disease by 1.65 (CI 95 % 1.5–2.37) times. The association of the risk of developing Parkinson's disease with the carrier of allelic variants of the APOE gene has been revealed. Carrier of the e3 / e4 genotype increases the risk by 2.08 (CI 95 % 1.18– 3.65) times, e4 / e4 genotype – by 3.53 (CI 95 % 0.90–13.86) times. It was determined that telomere length in buccal epithelial cells is shorter in patients with Parkinson's disease than in healthy individuals and correlates with telomere length in blood cells (r = 0.55; p < 0.01).