Diagnosis of Parkinson’s disease (PD) is often problematic because clinically it can be difficult to distinguish idiopathic PD from the other extrapyramidal disorders. It is known, that PD is caused either by environmental and genetic factors . Genetic mutations are the cause of familial form of PD and include genes PARK1-PARK18. The etiology of sporadic PD (SPD) is still not clear, but it is currently assumed that genetic susceptibilities, may be involved. It is suggested, that in pathogenesis of the SPD beside SNCA and PARK2 genes, may be involved also SPR (sepiapterin reductase gene) [PARK3] and HTRA2 (HTRA serine peptidase 2 gene)[PARK13] genes. The HTRA2 gene, also known as Omi, was found to be associated with PD in German population. However, some studies have indicated that some variants of HTRA2 may not be related to PD. SPR gene, which is located in the PARK3 linkage region is inconsistently associated with a risk of PD but significance of mutations in this gene as well as HTRA2 in PD is still not clear. The aim of the study was the analysis of the frequency of T637A/G SPR as well G421T, G1195A and C1210T mutations in HTRA2 gene in Polish patients with PD and in control group. Peripheral blood was collected from 89 patients with PD clinical diagnosis (42F and 47M, the avr. age 62 ± 10.15 years), and from 113 healthy donors (79F and 7M, the avr. age 55.5 ± 9.54 years). Genomic DNA was isolated using standard protocols. Genotyping was performed by PCR/RFLP using specific primers and restriction enzymes (SsiI, MboII, MvaI, MspI) and sequencing. The SPR gene analysis detected T637A mutation in 3 (3%) PD patients compared to 2 (2%) persons in the control group. Moreover, mutations G421T and G1195A of HTRA2 gene have been identified in 3 (3%) [G421T – 1%, G1195A – 2%] patients with PD and none of controls. Analysis of C1210T HTRA2 mutation detected no mutated variant both in PD patients group and in control group. It was also observed that the stage of the disease was 1–2 in Hoehn and Yahr scale and response to L-dopa was good in patients with T637A SPR and G421T, G1195A HTRA2 mutations. It was also observed some tendency for depression manifestation in PD patients with T637A SPR mutation. It can be concluded, that mutations of SPR and HTRA2 genes probably may be one of the risk factor for manifestation of PD. Thus, the results of this study suggest that analysis of T637A SPR and G421T, G1195A HTRA2 genes mutations may be an additional diagnostic and prognostic factor in PD patients in the future.
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