Assessment of risk factor variants of LRRK2, MAPT, SNCA and TCEANC2 genes in Hungarian sporadic Parkinson’s disease patients

• Published in: Neuroscience letters 2019-07, Vol.706, p.140-145
• Main Authors: Boros, Fanni A., Török, Rita, Vágvölgyi-Sümegi, Evelin, Pesei, Zsófia Gabriella, Klivényi, Péter, Vécsei, László
• Format: Article
• Language: English
• Subjects: Adult; Aged; Alleles; alpha-Synuclein - genetics; Female; Gene Frequency; Genetic Predisposition to Disease; Genetic risk factors; Genotype; Humans; Hungary; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 - genetics; LRRK2; Male; MAPT; Middle Aged; PARK10; Parkinson Disease - genetics; Parkinson’s disease; Polymorphism, Single Nucleotide; SNCA; tau Proteins - genetics
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2019.05.014

•G2385R and R1628P LRRK2 variants are absent in the Hungarian population.•The minor allele of the risk factor S1647T variant is more frequent among healthy male individuals compared to patients.•The protective rs356186 SNCA variant is significantly more frequent in homozygous form among controls than in PD patients.•The rs356186 SNCA variant is significantly more frequent in heterozygous form among LOPD patients compared to controls.•No significant differences were detected in the case of rs1491923, R1398H, N551K, rs2583988, rs1052553, rs10788972 variants. Parkinson’s disease is the second most common neurodegenerative disease. Lifestyle, environmental effects and several genetic factors have been proposed to contribute to its development. Though the majority of PD cases do not have a family history of disease, genetic alterations are proposed to be present in 60 percent of the more common sporadic cases. The aim of this study is to evaluate the frequency of PD related specific risk variants of LRRK2, MAPT, SNCA and PARK10 genes in the Hungarian population. Out of the ten investigated polymorphisms three are proposed to have protective effect and seven are putative risk factors. For genotyping, TaqMan allelic discrimination and restriction fragment length polymorphism method was used. LRRK2 mutations were investigated among 124 sporadic PD patients and 128 healthy controls. MAPT and SNCA variant frequencies were evaluated in a group of 123 patients and 122 controls, while PARK10 variant was studied in groups of 121 patients and 113 controls. No significant difference could be detected in the frequencies of the investigated MAPT and PARK10 variants between the studied Hungarian PD cases and controls. The minor allele of the risk factor S1647T LRRK2 variant was found to be more frequent among healthy male individuals compared to patients. Moreover, in the frequency of one of the investigated SNCA variant a significant intergroup difference was detected. The minor allele (A) of rs356186 is proposed to be protective against developing the disease. In accord with data obtained in other populations, the AA genotype was significantly more frequent among Hungarian healthy controls compared to patients. Similarly, a significant difference in genotype distribution was also found in comparison of patients with late onset disease to healthy controls, which was due to the higher frequency of AG genotype among patients. The frequencies of different gene variants show gr